THE UNIVERSITY OF TEXAS AT AUSTIN

GRADUATE PROGRAMS IN

biochemistry cell & molecular biology microbiology

Advancement to doctoral candidacy occurs after students pass the qualifying exam, form a dissertation committee, and complete the required graded courses. Graduate students normally reach this point by the end of the third year. Doctoral candidacy then allows students to focus on their research as they complete the Ph.D. degree. Graduation requires the completion of doctoral research, compilation of dissertation, and a final doctoral defense. A typical course schedule is as follows: * Year 1: Structure & Function of Proteins & Membranes (Mol 395G) Structure and function of proteins and membranes, catalysis of biological reactions, cellular reaction pathways and control Genes, Genomes, and Gene Expression (Mol 395J) Mechanisms of prokaryotic and eukaryotic DNA replication, repair and transcription; processing and localization of RNA transcripts; mechanism and regulation of RNA translation; regulation of gene expression from the perspectives of genes and genomes.

Physical Methods Biochemistry (BCH 387D) Theory of physical methods used in biochemistry and molecular biology. Structure and Function of proteins and nucleic acids (BCH 394) Quantitative methods used to evaluate the structure and dynamics of macromolecules including traditional and state-of-the-art kinetic methods. Current literature student seminar. Fall and Spring. (BCH 192G) Student seminar presentations covering current research topics. * Year 2: Supervised Teaching. Fall. (BIO398T) Instruction on successfully managing the role of instructor with emphasis on being an effective teaching assistant; training and practice in teaching techniques and professional presentations. Two elective courses BCH192G Research Qualifying exams occur in the spring * Year 3: (through completion of degree) Research

BCH192G (taken for six semesters) Annual meeting with dissertation committee The degree program currently requires students to serve as a teaching assistant for at least one semester after their first year. A variety of supervised teaching positions are available, involving laboratory sections, discussion sections, lecturing and grading. Students are matched to teaching positions based on their backgrounds and interests, as well as individual and faculty preference.

The ultimate goal of graduate training is for the student to develop into an independent scientific researcher.

cell and molecular biology graduate program

CMB students receive their initial training through a curriculum that combines a set of core courses with track-oriented elective courses. In addition to coursework, first-year students do three laboratory rotations with faculty of their choosing. Students join the laboratory of a Ph.D. mentor in May of their first year.

track research area of interest the following two courses are recommended or one of these may be combined with a track specific course or two track specific core courses may be taken: Cell Biology (Mol 395H) Mechanisms of growth control, cell regulation, mitosis, cell signaling, protein targeting, and the integration of these processes in various cellular processes. Genetics, Genomics and Epigenetics (Mol 395F) Forward and reverse genetics in model organisms, cancer genetics, comparative and functional genomics, epigenetic phenomena and mechanisms, RNAi and miRNAs, polyploidy and aneuploidy. Track specific core courses that may be taken in the spring of the first year: Bioinformatics & Computational Biology o CS394C Mathematical And Computational Biology In Computer Science o BIO384.2 Computational Biology--Nucleic Acids Biomolecular Structure & Function o CH387D Biophysical Methods o CH394 Structure and Function of Proteins and Nucleic Acids Chemical Biology & Drug Discovery o PHR388C Introduction to Bioorganic Chemistry

o PHR390N Biochemical And Molecular Toxicology o CHE384 Quantitative Molecular & Cellular Biology Plant Molecular Biology o BIO388E Plant Growth and Development To be admitted to candidacy, a student must complete coursework, pass Part One of the qualifying exam (Spring of year two), and pass Part Two of the qualifying exam within a year of passing Part One. The final stage to receive the doctoral degree is to accomplish creative, independent research under the guidance of a faculty mentor, and to document that research in a scholarly dissertation, as well as publications. cell and molecular biology tracks The CMB program is interdisciplinary and crosses many areas of biological and chemical research. The tracks are points of organization of related research and provide communities within the larger program for students and faculty:

Fall Core Courses

Genes, Genomes, and Gene Expression (Mol 395J) Mechanisms of prokaryotic and eukaryotic DNA replication, repair and transcription; processing and localization of RNA transcripts; mechanism and regulation of RNA translation; regulation of gene expression from the perspectives of genes and genomes. Structure & Function of Proteins & Membranes (Mol 395G) Structure and function of proteins and membranes, catalysis of biological reactions, cellular reaction pathways and control Student Seminar (Mol 190) First-year students practice critical reading, presenting and discussing the primary literature.

bioinformatics & computational biology

Comprised of an interdisciplinary and collaborative group of researchers who are interested in topics that span all aspects of biology, biochemistry, biophysics and neurobiology. A distinguishing characteristic of the students in this track, in contrast with the students 4

Spring Core Courses

Students take two courses in the spring in addition to Mol 190. If a student has not identified a particular

in the other Cell and Molecular Biology tracks, is the magnitude and sophistication of the computational component of their project. This includes but is not limited to - the analysis of large data sets, more exhaustive computational analysis, develop novel types of analysis, and write sophisticated computer programs to analyze their data. Interactions and collaborations with investigators from other CMB tracks, Biostatistics, and the departments of Computer Science, Engineering, and Biomedical Engineering are encouraged. Students who do well in this track frequently demonstrate individual initiative in generating and executing projects. Students are allowed to have more than one CMB mentor during their graduate careers to develop and implement interdisciplinary projects.

with this track have a broad diversity of research interests including topics such as signal transduction, membrane traffic, cell polarity and motility, regulation of gene expression, cell-cell interactions, specification of cell identity, spatial patterning of developing embryos and evolution of developmental mechanisms. There is also a strong commitment to imaging techniques including scanning laser confocal microscopy, in vivo imaging of developmental processes, measurements of intracellular ion concentrations and electron microscopy.

The track includes diverse fields of biology ranging from cellular processes including DNA recombination, repair, transcription, splicing, translation, genomics, gene silencing, chromatin modifications, epigenetic mechanisms, RNA interference, microRNA regulation, and control of the cell-division cycle, to molecular evolution as well as human cancers and other diseases. Faculty affiliated with this track represent a broad range of research interests and experimental systems from phage, virus, and bacteria to yeast, plants, flies to mice and humans.

chemical biology & drug discovery

Research at the chemistry-biology interface that focuses on the discovery and development of drugs and health-related technology. The faculty members have extensive experience in the synthesis of organic and biopolymer therapeutics, the development of high-throughput screens and assays, the application of three dimensional structure determination and modeling techniques to drug design, and the identification and evaluation of molecular targets and therapeutics, and the evaluation of the toxic action of drugs and drug candidates.

neurobiology
Primarily interests include applying cellular and molecular techniques to study the nervous system. Our faculty have wide ranging research interests that touch on most of the present frontiers in neuroscience, including specification of neuronal cell fates, integration of information by synapses and dendrites, alterations in neuronal circuits as a consequence of experience, drug and alcohol addiction, sensory processing, transmitter release, repair of neuronal injuries, hormones and behavior, learning and memory, and gene expression.

biomolecular structure & function

Research on how proteins and nucleic acids are organized, and their structure and function in cells. Using powerful techniques such as X-ray crystallography or NMR spectroscopy, as well as biochemical or biophysical methods, models of macromolecules and their properties are used to explain the molecular basis of catalysis, recognition and disease.

molecular genetics
Fundamental questions are asked concerning inheritance and changes of genetic information in living organisms. In molecular terms, this information is encoded at the level of DNA, RNA, and/or protein.

plant molecular biology

The Plant Molecular Biology Track brings diverse faculty together that use plants or photosynthetic organisms as model systems for the study of basic biological processes, genomics, and biofuels.

cell & developmental biology

Research on the cell biology and development of animal, plant and microbial systems. Faculty affiliated

research opportunities
Interdisciplinary Interactions The graduate programs offer a variety of interdisciplinary research opportunities including: Research seminar series presented weekly by outstanding scientists from across the US and the world. The Institute for Cellular and Molecular Biology retreat features exciting new faculty, student and postdoctoral research each fall Poster sessions during recruitment visits in the spring provide an opportunity for new interactions. DNA Sequencing Facility
The DNA Sequencing Facility provides DNA sequencing, fragment analysis, quantitative real-time PCR, NanoDrop spectrophotometer, phosphor and fluor imaging, a plate reader, and automated liquid handling. Automated DNA sequencing is performed using capillary-based Applied Biosystems 3730 DNA Analyzers. These instruments offer high throughput and sensitivity with a capability of handling more than 1400 samples per day, with reads greater than 700 base pairs and a success rate of over 90 percent. The AB 3730 and 3730XL are also used for

the analysis of microsattelites, AFLP, SNPs,tRFLPs and other fragment applications. Quantitative real-time PCR is run on an Applied Biosystems ViiA 7s. These instrument allow researchers to analyze gene expression using allelic discrimination and SNP analysis in 96 or 384 wells. The quantification of DNA, RNA, and proteins using only one or two microliters without a cuvette is performed on the NanoDrop spectrophotometer. The Typhoon 9500 Imager measure and image radioactive signals using from gels or membranes using phosphor screens and fluorescence from gels, membranes, TLC plates, and microtiter plates. Other instruments include Beckman Biomek NX and FX pipetting robots, and Berthold NightOWL. The NightOwl is available for low-light imaging of luminescence or fluorescence in plants or animals. More information about the facilitys services is available at http://www.icmb.utexas.edu/core/DNA/.

Proteomics Facility. The facility provides a variety of proteomics analyses, as well as related protein support services. It is administered by ICMB and the College of Pharmacy with additional support from the Cancer Prevention and Research Institute of Texas. Two state-of-the-art Thermo Orbitrap Elite mass spectrometers with Dionex UPLC chromatography systems provide qualitative proteomics analyses,

with Scaffold software used for data validation and visualization. Quantitative proteomics uses stable isotope labeling such as iTRAQ or TMT reagents, as well as spectral counting and peak area label free methods. Protein post-translational modifications such as phosphorylation, acetylation, methylation, oxidation, and ubiquitination are identified from the high resolution data. Associated proteolytic digest and phosphopeptide enrichment protocols are available as well. Protein molecular weight determination is conducted on the AB Sciex 4000 QTRAP. Protein N-terminal sequencing is offered as a service for determination of cleavage sites. Selfservice instruments are available for researchers to use for IR based protein quantitation, FPLC separations, and mass spectrometry measurements, with training provided by core staff. More information about the facilitys services is available at http://www.utexas.edu/pharmacy/divisions/
pharmtox/core/

Mouse Genetic Engineering Facility

TThe primary mission of the Mouse Genetic Engineering Facility (MGEF) is to produce genetically modified mice for the UT community. This includes the generation of transgenic mice (pronuclear injections), gene targeting in mouse embryonic stem cells by homologous

recombination (electroporation and selection), and generating chimeric mice (blastocyst injections). Additional services include embryo cryopreservation and long-term storage, recovery of frozen embryos, and rederivation of mouse strains to sterile, pathogen free status. More information on services is available at http://www.icmb.utexas.edu/facilities/mouse/.

Genomic Sequencing & Analysis Facility

The ICMB GSAF provides next-generation DNA sequencing services including sample preparation and sequencing for a wide variety of applications. We have two Illumina HiSeq 2500s and two Illumina MiSeq sequencers, and have operated other next-generation DNA sequencing systems in the past. We have a variety of quality control tools to test library quality and support users who create their own libraries or who wish to outsource this service to the GSAF. The GSAF has a staff of experienced technicians capable of performing many RNA and DNA library preps including directional RNA-seq libraries, small RNA libraries, normalized cDNA libraries, whole genome DNA libraries, enriched DNA libraries (e.g. exome capture libraries), and many other more specialized library types. Our data systems are integrated with the Texas Advanced Computing Center (TACC) supercomputer resources, and we work closely with the CCBB/CSSB Bioinformatics Consulting Group who consult and analyze NGS data. More information about our services is available at: http://www.gsaf.cssb. utexas.edu

Microscopy and Imaging Facility

TThe ICMB Microscopy and Imaging Facility provides extensive microscopic equipment and services for ultra-structural analysis. The facility offers assisted use and training on its instrumentation and consultations on microscopy-and spectroscopy-related research. Equipment in the facility includes: scanning and transmission electron microscopes, confocal, superresolution, and wide-field fluorescence microscopes, cryo, paraffin, ultra microtomes, laser micro-dissection, a stereology system, and multiple compound light microscopes and stereoscopes. Furthermore, the facility provides state of the art image processing and analysis software. The Microscopy and Imaging Facility also manages the Flow Cytometry Laboratory which houses several instruments capable of fluorescence-based cell analysis and cell sorting. More information on services is available at: http://www.icmb.utexas.edu/core/ Microscopy.

houses two x-ray generators and three detectors as well as accompanying cryo-cooling devices. The Rigaku MicroMax 007 generator provides some of the strongest radiation outside of synchrotron sources and enables data collection on crystals with unit cell dimensions up to 300 . A Phoenix liquid-handling robot can set up hundreds of crystallization experiments within minutes. A CrysCam digital microscope and three high-magnification Leica stereomicroscopes aid in the detection and manipulation of crystals. Four 3D-enabled workstations loaded with the most current crystallographic software are available to help users build and refine macromolecular structures. Dynamic light scattering and differential scanning fluorimetry instruments are also

Macromolecular Crystallography Facility

The Macromolecular Crystallography Facility allows users to determine the three-dimensional structures of macromolecules using x-ray diffraction. The Facilty

These are exciting times for the entire field of biological science, and ours is a uniquely broad and multidisciplinary graduate program that brings together faculty from more than ten different academic departments
- Alan Lambowitz, Director, Institute for Cellular and Molecular Biology 9

Seema Agarwala
Molecular Biosciences Ph.D., State University of New York http://www.utexas.edu/neuroscience/Neuroscience/SeemaAgarwala/index.html

faculty

During embryogenesis, neurons learn of their cell-fates and are assigned to specific brain nuclei (nucleogenesis), which organize brain connectivity and function. Little is known about how such complex patterning is achieved during vertebrate development. We study these processes in the mouse and chick midbrain, where clinically important nuclei such as the oculomotor complex (involved in eye movements) and midbrain dopaminergic neurons (involved in Parkinsons disease and addictive behaviors) reside. I have previously shown that the signaling molecule, Sonic Hedgehog, is sufficient to specify the entire ventral midbrain (organogenesis). We are now examining the downstream transcriptional mechanisms that allow this single molecule to specify multiple cell and nuclear fates. Experimental approaches include in vivo gene misexpression by electroporation (in chick and mouse), protein misexpression using coated-beads, and gene silencing by novel strategies such as RNA interference and morpholino oligonucleotides and microarray analyses. Manipulations in the chick are complemented with gene expression analyses of mutant chicks and mice with defects in midbrain patterning.

Richard Aldrich
Neuroscience Ph.D., Stanford University http://clm.utexas.edu/AldrichLab/ Ion channels are the molecular units of electrical signaling in cells. They are proteins that regulate the movement of ions--such as sodium, calcium, and potassium--into and out of cells. They are responsible for the conversion of external sensory signals to the electrical language of the nervous system and for the integration of these signals to generate appropriate behavior. Ion channels are also important for the generation and regulation of the heartbeat, for contraction of muscles, and for the release of hormones in the bloodstream. The body contains a large variety of ion channel types, specialized to select for certain species of ions and to selectively open and close in response to a number of different stimuli, such as the binding of a neurotransmitter molecule or a change in the voltage that exists across a cells membrane. Work in the Aldrich laboratory is directed towards understanding the mechanisms of ion channel function and the role of ion channels in electrical signaling and physiology. This research relates to transduction, processing, and transmission of information in the nervous other physiological systems and to basic mechanisms of coupled conformational changes in signaling proteins. We use a combination of molecular biology, electrophysiology, biophysics, cellular and systems physiology, and computational biology.

Hal Alper
Chemical Engineering Ph.D., Massachusetts Institute of Technology http://www.che.utexas.edu/alper_group/index.html The goal of metabolic and cellular engineering is to endow novel and useful properties to cellular systems. Recent advances in molecular biology and genetic engineering empower metabolic engineers with an increasing ability to create any desired cellular modification. The integration of these approaches with an ever-increasing database of knowledge about these cellular systems (due in part to genomic sequencing efforts) provides an unprecedented opportunity to engineer cellular systems. Our research group focuses on the integration and implementation of these tools and knowledge for the design, production, and elicitation of phenotypes relevant to biotechnological processes and medical interest. Using a variety of host systems including microbial (eg. Escherichia coli), fungal (eg. yeast), and mammalian (eg. Chinese Hamster Ovary (CHO) cells), we seek to develop the necessary genetic tools and methodologies for creating industrially-relevant organisms for biomolecules, biofuels, and biopharmaceuticals. To accomplish this task, traditional pathway engineering will be utilized in conjunction with novel tools for introducing genetic control (such as global Transcription Machinery Engineering, promoter libraries, and gene mutagenesis).

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Eric V. Anslyn
Chemistry Ph.D., California Institute of Technology http://research.cm.utexas.edu/eanslyn/ Our research is oriented at developing artificial enzymes and sensors by synthetic and combinatorial library methods. Our synthetic projects are targeted to phosphodiester hydrolysis, enolate alkylations, and polysaccharide cleavage. The combinatorial library projects are focused on forming abiotic secondary structure via hydrogen bonding in polythioureas, and polyguanidiniums. In each synthetic project, natural systems such as enzymes and transport proteins are carefully examined, and mimics are designed with the aid of computer modeling. The mimics are evaluated as to their success at performing the desired catalytic or sensing event, and then redesigned for optimization. In each combinatorial library project, solid phase synthesis of novel polymers are pursued incorporating scaffolds the create binding cavities and specific molecular recognition events. The novel polymers are tested for binding, catalysis, and sensing functions by screening the libraries for activity.

Dean R. Appling
Molecular Biosciences Ph.D., Vanderbilt University http://research.cm.utexas.edu/dappling/ We are interested in the organization and regulation of metabolic pathways in eukaryotes. Eukaryotic cells are composed of many different compartments, such as cytoplasm, mitochondria, and nuclei. Although each of these compartments exhibits a distinct set of metabolic processes, they must all communicate with each other for the cell to function properly. Understanding how these processes are organized and controlled represents the next frontier in the study of metabolism. We have focused our efforts on folate-mediated one-carbon metabolism. This set of pathways is found in all cells and organisms, is central to fundamental processes such as nucleic acid and protein synthesis, and occurs in multiple compartments. We are particularly interested in mitochondrial pathways and processes. We utilize a wide variety of biochemical and molecular genetic techniques, including metabolic engineering, to study the organization of these pathways in both mammalian and fungal systems with a particular emphasis on mitochondrial processes.

Nigel Atkinson
Neuroscience Ph.D., Pennsylvania State University http://w3.biosci.utexas.edu/atkinson/index.html The fundamental question that drives us is: How are ion channel genes regulated and what are the consequences of this regulation? To address this question we have been using the slowpoke gene of Drosophila as a model. The slowpoke gene encodes the BK-type Ca2+-activated K+ channel. In insects and mammals these channels are used in both nervous tissue and muscle. In humans this channel plays a central role in controlling blood pressure. Our work shows that slowpoke is homeostatically regulated. Treatments that reduce neural excitability enhance slowpoke expression while treatments that increase activity reduce slowpoke expression. Both of these changes are postulated to shift the nervous system back towards a more normal level of excitability. In this vein, we have developed a Drosophila model of tolerance to drugs of abuse. In this model, flies sedated one time with either ethanol or an organic solvent acquire tolerance to solvent sedation. Tolerance is reduced drug response responsiveness caused by prior drug exposure and is a factor that leads one to addiction. We have shown that sedation also induces slowpoke expression and that slowpoke is absolutely required for the production of behavioral tolerance. Electrophysiological assays show that increased slowpoke enhances neural excitability in a manner postulated to resist sedation and to produce tolerance. At this time, we are identifying the transcriptional mechanisms that slowpoke uses to monitor and respond to state of neural activity. We have observed that drug sedation causes changes in chromatin remodeling and how that these changes leads to increased channel expression.

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Adela Ben-Yakar
Mechanical Engineering Ph.D., Stanford University http://research.engr.utexas.edu/benyakar// Dr. Ben-Yakar specializes on advanced applications of femtosecond lasers in life sciences, nonlinear microscopy, plasmonic nanoengineering, and nanotechnology. She investigates the fundamentals of femtosecond laser interaction with biological tissues and nanomaterials to develop novel techniques such as laser nanosurgery and 3-D micro-/nano-fabrication techniques. Dr. Ben-Yakar is a faculty member of the Thermal/Fluid Systems program of the Mechanical Engineering Department. She has served on the College of Engineering faculty since 2004. Dr. Ben-Yakar received a 2005-2006 Research Grant for her work on Femtosecond Laser Nano-Surgery of Carbon Nanostructures.

Halil Berberoglu
Mechanical Engineering Ph.D., University of California, Los Angeles http://www.me.utexas.edu/~berberoglulab/ In my laboratory, we are interested in harnessing the power of sun through biological and artificial bio-mimetic routes for producing clean and renewable fuels. Currently we are studying algal and cyanobacterial systems for carbon neutral biodiesel and bio-hydrogen production. In particular we are interested in modeling and optimizing the growth and product formation kinetics in response to process parameters such as total and spectral irradiance, temperature, pH and various nutrient concentrations. In order to facilitate this task we are developing micro-fluidic based photobioreactors and non-invasive measurement techniques that will enable high throughput experiments to be conducted. Also, we are developing artificial photosynthetic systems that will use solar energy for efficient and cost effective conversion of CO2 directly into useable fuels and other value added products. This task involves using synthetic systems such as dye sensitized photo-electrochemical cells for efficient photo-electron generation and coupling of these electrons to enzyme and/or synthetic catalyst systems for hydrocarbon fuel production.

George Bittner
Neuroscience Ph.D., Stanford University http://www.utexas.edu/neuroscience/Neurobiology/GeorgeBittner/index.html We research cellular/molecular mechanisms of plasmalemmal repair and nerve regeneration. That is, we examine various biophysical, biochemical, or molecular mechanisms by which lesioned neurons repair lesions to their plasmalemma and regenerate axons. We are particularly interested in the role of calcium and axonal proteins in plasmalemmal repair and how such plasmlemmal repair relates to axonal regeneration. we are also interested in hoe polyethylene glycol (PEG) can be used to repair severed axons so that axonal continuity and function can be permanently repaired within minutes after applying PEG to rejoin severed axons.

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Karen S. Browning
Molecular Biosciences Ph.D., University of Illinois at Urbana-Champaign http://research.cm.utexas.edu/kbrowning/ My research focuses on the initiation of protein synthesis in higher plants. We are seeking a molecular description of the process in which initiation factors (eIF4A, eIF4B, eIF4F, eIF3, eIF2 and PABP) select, prepare and bind messenger RNA to the 40S ribosome. Plants have a unique second form of eIF4F, and we are using a variety of methods (genetic knockouts, gene silencing, DNA arrays, etc.) to discover the function of this novel initiation factor. We are also interested in the features of messenger RNAs that make some messenger RNAs translate more efficiently than others. We are studying a plant viral RNA, satellite tobacco necrosis virus, that appears to use a region in the 3 untranslated region (3 UTR) to facilitate cap-independent translation by recruiting eIF4F. eIF4F is normally bound to the 5 cap of mRNAs during initiation, so the use of the viral 3 UTR to facilitate initiation at the 5 end represents a novel mechanism. We are using a variety of techniques to study the interactions of initiation factors with each other & with messenger RNAs (biochemical assays, site-directed mutagenesis, crystallography, yeast three-hybrid system, fluorescence, etc.). From our studies we hope to gain a better understanding of the protein-protein & protein-RNA interactions that must occur for successful initiation of translation of messenger RNA.

James J. Bull
Integrative Biology Ph.D., University of Utah http://www.zo.utexas.edu/faculty/antisense/ Evolutionary genetics: molecular, classical and theoretical, at a gene and genome level is the focus of my research. Topics include the evolution of virulence, evolutionary robustness and redundancy, the genetic basis of adaptation, and phylogeny reconstruction. Experimental systems are developed in which evolution occurs over short time periods in the laboratory; the evolved lines are then analyzed at the molecular genetic level, so that the course of evolution is known with certainty. Research organisms are chiefly bacteriophage, enabling complete genome sequencing. Students are encouraged to initiate their research on a well-defined model system to gain experience and then expand their research to problems of their own design.

Z. Jeffrey Chen
Molecular Biosciences Ph.D., Texas A&M University http://polyploidy.biosci.utexas.edu We study genetic and epigenetic mechanisms for gene expression changes in polyploids. Polyploidy, or whole-genome duplication (WGD), is an evolutionary innovation for all eukaryotes including some animals and many plants. The common occurrence of polyploidy suggests an evolutionary advantage of having multiple sets of genetic material for adaptive evolution. However, increased gene and genome dosages in autopolyploids (duplication of a single genome) and allopolyploids (combination of two or more divergent genomes) often cause genomic instabilities, chromosomal imbalances, regulatory incompatibilities, and reproductive failures. Aneuploid and polyploid cells in animals and humans are often associated with carcinogenesis. Therefore, new polyploids must establish a compatible relationship between alien cytoplasm and nuclei and among divergent genomes, leading to rapid changes in genome structure, gene expression, and developmental traits such as fertility, inbreeding, apomixis, flowering time, and hybrid vigor. The underlying mechanisms for these changes are poorly understood. We employ genetic and biochemical approaches in combination with DNA microarrays, deep-sequencing, and bioinformatic tools to investigate how changes in DNA sequences, cis- and trans-acting factors, chromatin modifications, RNA-mediated pathways, and regulatory networks modulate silencing and activation of homoeologous genes, giving rise to phenotypic variation in polyploid plants and agricultural crops, many of which have increased biomass and enhanced traits. Elucidating mechanisms for polyploidy may ultimately reveal new approaches to reactivate or silence endogenous genes and lead the way to improve future applications of biotechnology in agriculture and medicine.

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Lydia Contreras
Chemical Engineering Ph.D., Cornell University http://contrerasgroup.wordpress.com/ Our research combines biomolecular engineering, genetic studies and computational modeling to understand molecular features that lead to the specific recognition and interaction of RNAs and proteins. We apply fundamental concepts that emerge from experimental (and computational) work to develop novel applications that could beneficially impact human health. Overall research interests: * RNA-protein interactions, RNA-protein folding * Novel molecular tools for intracellular studies of RNA-metabolism * Protein engineering for novel mechanisms of molecular recognition * Diagnostics for RNA-related diseases * Discovery of drugs targeting RNAs * Optimization strategies for therapeutic RNA/protein expression

David Crews
Integrative Biology Ph.D., Rutgers University http://www.utexas.edu/research/crewslab/ One of my research programs focuses on sex determination as a case study in how evolution has produced very different mechanisms for achieving the same end. Here I take advantage of the fact that in many reptiles the sex of the offspring depends on the incubation temperature of the egg, a process known as temperature-dependent sex determination (TSD). One question concerns how the physical stimulus of temperature is transduced into a physiological stimulus that operates ultimately at a molecular level to determine an individuals gonadal sex. In this work I use the red-eared slider turtle as the animal model system. I have demonstrated that sex steroid hormones are the physiological equivalent of incubation temperature, serving as the proximate trigger for male and female sex determination. Temperature appears to accomplish this end by acting on genes coding for steroidogenic enzymes (e.g., steroidogenic factor 1 and aromatase) and sex steroid hormone receptors (e.g., estrogen and androgen receptors), and other transcription factors and signaling molecules (e.g., Sox9, Wnt4, FOXL2, Mis, and Pumilio). Phylogenetic analysis indicates that TSD is the precursor of sex determination by genotypic mechanisms (e.g., sex chromosomes).

Richard Crooks
Chemistry Ph.D., University of Texas at Austin http://rcrooks.cm.utexas.edu/ Parallel replication of DNA and RNA arrays. We recently discovered a new method for replicating nucleic acid microarrays. Such arrays are presently used for genomic analysis, and within the next few years are expected to find their way into doctors offices as part of the new era of personalized medicine. Our approach for replicating microarrays is illustrated in the figure. In the first step, a DNA master array is prepared using suitable templates. Next, a primer bearing a biotin group is annealed to the distal end of the template DNA, and then it is extended by a polymerase-catalyzed surface reaction (step b). In step c, a streptavidin-modified poly(dimethylsiloxane) (PDMS) monolith is brought into contact with the DNA master microarray. Finally, the PDMS and master-array surfaces are mechanically separated. This results in transfer of the DNA complements to the PDMS replica surface (step d). Many such replicas can be prepared from a single master array. This approach has been improved in many ways since it was reported. For example, replica DNA microarrays can be prepared from a zip code master array having short zip code oligonucleotides. The use of a zip code master provides a means to fabricate replica DNA microarrays having any configuration from the single, universal zip code master array. This same approach can be used to replicate other types of arrays. For example, we recently reported fabrication of RNA replica arrays from DNA masters. Because this is a new analytical method, there many unanswered questions that we are just starting to think about: what biomaterials, other than nucleic acids, can be used with this method, what happens on the molecular level during transfer, and how many of the complements are transferred to the replica?

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Arturo De Lozanne
Molecular Biosciences Ph.D., Standford University School of Medicine http://www.zo.utexas.edu/faculty/delozanne/adlab.html We are interested in defining the molecular basis of the lysosomal disorder known as the Chediak-Higashi Syndrome. This disease is caused by mutations in a very large gene and result in the loss of a large protein known as Lyst. The size and low abundance of this protein have impaired the detailed analysis of its function and how its absence leads to the dysfunction of lysosomes in CHS patients. We have established a simple model system to study the molecular function of Lyst and closely related proteins in the organism Dictyostelium discoideum. We have shown that the loss of a similar protein in this organism results in the same lysosomal defect. Our approach is to study the phenotype of specific mustants using a variety of cell biological techniques including imaging of GFP-labeled proteins. Our studies will help us understand better the human disease and design potential therapies.

John DiGiovanni
Pharmacy and Nutritional Sciences Ph.D., University of Washington School of Medicine, Seattle http://he.utexas.edu/directory/digiovanni-john Research in my laboratory has focused on understanding how cancer develops and on the identification of novel targets, mechanisms and strategies for cancer prevention. Cancer is a disease involving gene-environment interactions and therefore understanding both environmental influences as well as genetic factors is key to developing the most effective strategies for preventing cancer. In addition, understanding the early cellular, biochemical and molecular changes that transform normal cells into cancer cells is essential if we are to eventually eradicate cancer as a major human disease. One major research area focuses on identifying specific cellular signaling pathways that are disrupted during tumor development and progression. Signaling pathways currently under study include the PI3K/Akt/mTOR pathway and Signal Transducers and Activators of Transcription (Stats), especially Stats1,3 and 5. Another important research area involves studies aimed at identifying the target cells (i.e., stem/progenitor cells) for tumor development. Another area of research involves identifying genes that confer susceptibility to environmentally-induced cancer. These studies have used genetic crosses between sensitive and resistant mice to map genes involved in the promotion of skin tumors in mice. Using this approach we recently mapped and identified a gene (Gsta4) on Chr 9 that is involved in susceptibility to skin tumor development in mice. We also found that polymorphisms in this gene are risk alleles for human nonmelanoma skin cancer (both basal cell carcinoma and squamous cell carcinoma). We are currently examining this gene in other human cancers and also working to identify genes in other regions of mouse chromosomes identified from our initial screen that harbor susceptibility loci. Cancers currently under study in the laboratory include skin cancer (both melanoma and non-melanoma skin cancers), prostate cancer, head and neck squamous cell carcinoma and lymphoma.

Michael Drew
Neuroscience Ph.D., Columbia University http://clm.utexas.edu/mdlab/ A broad aim of my research is to understand how adult hippocampal neurogenesis influences learning and cognition. The work is based on growing evidence that adult neurogenesis constitutes a functionally and, perhaps, clinically significant form of brain plasticity. Neurons are added to the adult hippocampal formation of all mammalian species studied to date, and the cells that are born appear to impact both cognitive and emotional aspects of hippocampal function. Manipulations that suppress adult neurogenesis impair performance in some hippocampus-dependent learning tasks, and adult neurogenesis is bi-directionally regulated by stimuli that affect the risk for emotional disorders. For instance, psychosocial stress potently suppresses hippocampal neurogenesis, while exercise, environmental enrichment, and virtually all antidepressant treatments stimulate adult hippocampal neurogenesis. My approach to understanding the functional significance of adult hippocampal neurogenesis relies on inducible genetic manipulations in mice, combined with rigorous behavioral analysis, and addresses questions such as (1) what underlying psychological processes depend on adult-generated neurons, (2) how do decreases or increases in adult neurogenesis affect these processes, (3) and what special properties of adult-generated neurons are instrumental in producing these effects?

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Ron Elber
Chemistry / Biochemistry Ph.D., Hebrew University of Jerusalem http://research.cm.utexas.edu/relber/ Two thrusts in computational biology are considered in the laboratory of Ron Elber in the Institute of Computational Engineering and Sciences (ICES): (i) The study of the dynamics and function of proteins and RNA, and (ii) The evolutionary processes that led to the set of biological molecules that we see today. We are particularly interested in atomically detailed descriptions of bio-molecular processes at time scales relevant to biology. The high sensitivity of these molecules to mutations and changes in the environment strongly suggests that atomically detailed modeling is desirable. Examples for studies of type (i) include allosteric transitions of proteins (microseconds), conversion of chemical to mechanical energy (milliseconds), ligand binding and protein-RNA interactions (milliseconds to seconds). There is a time scale gap between computations and experimental measurements that may exceed fifteen orders of magnitude in time. These observations are not accessible to straightforward modeling. A major thrust of the Center is therefore the development and application of novel techniques to bridge the temporal gap and coarse-grain calculations of time. The second thrust in Elbers laboratory is on molecular evolution. Proteins (and RNA) undergo mutations and adjustments of their function during the process of evolution. As such, they provide useful fingerprints of past, present, and perhaps also future adaptation. We study the implication of molecular stability on evolution. For example, proteins that are more stable are found to evolve faster. The laboratory develops a network picture of protein evolution within and between folds which is useful as a core model for molecular evolution. In other bioinformatic applications we focus on determining protein structures and on protein-protein interactions. The models are studied on a high-performance computing platform. A new supercomputer with 1,600 computing cores is installed in Texas Advance Computing Center (TACC) for the use of Elbers laboratory.

Andy Ellington
Molecular Biosciences Ph.D., Harvard University http://ellingtonlab.org The Ellington lab is primarily interesting in the evolutionary engineering of molecules, pathways, and organisms, and the application of these efforts to real world problems. In particular, we evolve functional RNA molecules that can function as diagnostic and therapeutic reagents, including RNA molecules that inhibit the replication of HIV-1 and tumor cells. We combine functional RNAs and other components into synthetic genetic circuits that can be used to control gene expression during gene therapy. We are also involved in the development of novel chimeras between biology and chemistry, including minimal replicators that can evolve outside of cells, light-dependent signal transduction pathways, and organisms that utilize unnatural amino acids in their proteomes.

Walter Fast
Pharmacy (Medicinal Chemistry) Ph.D., Northwestern University http://www.utexas.edu/pharmacy/divisions/medicinalchem/faculty/fast.html We are interested in merging protein engineering technologies with more classical biochemical approaches in the investigation and manipulation of three enzyme systems: 1. Quorum sensing, a language that some bacteria use to communicate with each other. Disrupting this communication can prevent harmful infections that form biofilms. 2. Arginine modification: Arginine methylation and methyl- arginine hydrolysis are emerging as important activities in signal transduction pathways. However, little is known about the mechanism or inhibition of the enzymes that catalyze these reactions. 3. Prodrug activating enzymes: The prodrug approach seeks to limit side-effects of anticancer compounds. Protein engineering of a human protein to specifically activate prodrugs would allow for developing unique prodrug-enzyme pairs. The Fast lab uses rational & combinatorial mutagenesis, library screening & selection, small molecule synthesis, steady-state & pre-steady state kinetics, and various biophysical techniques to understand the structure & reactivity of these enzymes. These studies are then related to the larger questions of enzyme evolution and therapeutic application.

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Ernst-Ludwig Florin
Physics Ph.D., Technical University of Munich http://chaos.utexas.edu/florin.html Our long-term goal is to analyze and understand specific cellular processes from the single molecule level up to an entire cellular response. We currently investigate the molecular mechanics of microtubules, the nano-mechanics of vesicle fusion mediated by the SNARE complex, mechanics of molecular motors, elementary steps in molecular recognition, lateral organization of the plasma membrane (lipid rafts) and membrane bound signal transduction by receptor tyrosine kinases (RTKs). Our work includes the development of novel types of high-resolution microscopes for single molecule and single cell studies and their combination with conventional light microscopic and scanning probe techniques.Together with our collaborators in molecular biology, cell biology, and theoretical physics, we aim to get a complete picture of selected processes from modeling molecular events (molecular dynamic simulations) to the description of complex behavior of biological material.

George Georgiou
Chemical Engineering & Molecular Biosciences Ph.D., Cornell University http://www.che.utexas.edu/georgiou/home.htm Dr. Georgious group is working on both biotechnology and mechanistic biology problems. In biotechnology, his group is focusing on the development of protein engineering and combinatorial library screening technologies for facilitating the discovery of new therapeutic antibodies and enzymes. Current projects include the development of antibodies for bacterial infectious diseases, such as anthrax and therapeutic enzymes for certain forms of cancer. These studies are accompanied by detailed analysis of protein structure function to aid the understanding of antibody-antigen recognition and of enzymatic catalysis. In related studies, Dr. Georgious group is developing technologies for the preparative expression of recombinant proteins in bacteria and other host cells. About half of Dr. Georgious group is working on problems related to fundamental mechanistic issues in protein biogenesis. These include; (1) oxidative protein folding and redox control in bacteria; (2) the translocation of proteins across the membrane via the Twin Arginine Transporter (Tat) pathway; (3) the mechanism of RNA degradation in E.coli.

Nace Golding
Neuroscience Ph.D., University of Wisconsin http://w3.biosci.utexas.edu/golding/Home.html Neuronal dendrites are elaborate, tree-like structures that receive up to thousands of excitatory and inhibitory synaptic connections. The morphology and electrical properties of the dendrites strongly influence the way in which synaptic activity sums together and is ultimately translated into new patterns of action potential firing in the axon. This translation process, called dendritic integration, is the fundamental means by which neurons regulate what synaptic information is communicated to the neurons network targets. My research focuses on identifying the mechanisms by which dendrites shape synaptic activity and action potential firing, as well as understanding how these mechanisms contribute to the neurons functional role. An additional focus is on how dendritic properties influence changes in synaptic strength that, in turn, underlie some forms of learning and memory.

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Vernita Gordon
Physics Ph.D., Harvard University http://chaos.utexas.edu/people/faculty/vernita-gordon Intercellular and extracellular interactions drive the formation of multicellular systems and the emergent behaviors that characterize these systems. In my group, we work to understand how cells interact with each other and with their environment, and how these interactions play into the formation and responses of multicellular systems. We use a combination of biological and physical tools in a highly-interactive, multidisciplinary environment, to probe interactions on molecular, cellular, and multicellular lengthscales.

Andrea Gore
Pharmacy Ph.D., University of Wisconsin http://www.utexas.edu/pharmacy/divisions/pharmtox/faculty/gore.html My laboratory is interested in the mechanisms by which the brain controls reproductive development and aging. We are focusing on a group of neurons in the hypothalamus that synthesize and release a peptide, gonadotropin- releasing hormone (GnRH), that is the primary molecule controlling reproductive function throughout the life cycle. In order to better understand the mechanisms by which GnRH neurons change, and the central and peripheral factors that regulate GnRH neurons, we are characterizing changes in GnRH release, gene expression, neuroanatomy and physiology in normally developing male and female rats. We are also studying how perturbations of this system (e.g. by environmental toxicants, or by pharmacological agents acting on receptors on GnRH neurons) disrupt this process, resulting in aberrant reproductive processes. These experiments are intended to provide basic information about the neural mechanisms of normal reproduction, as well as to develop interventions to protect against environmental factors that may perturb normal reproductive development.

Ellen Gottlieb
Molecular Biosciences Ph.D., Yale University http://www.icmb.utexas.edu/cmb/tracks/details.asp?track=MG&facultyID=1566 A primary focus of our work is to decipher the molecular mechanisms governing the exciting field of RNA transport/localization. This process is of fundamental importance in development and differentiation, and its disruption can result in birth defects, infertility and certain nerve-muscle disorders. We take a multidisciplinary approach involving techniques from molecular biology, biochemistry, cell biology and genetics. Extensive use is made of synthetic RNA transcripts, cellular extracts and the battery of techniques used to investigate RNA-protein interactions in other steps of RNA biogenesis. Our model systems include Drosophila development and human neuromuscular disease. Efforts have included: 1) identifying composite discrete cis-acting RNA localization signals; 2) employing these signals to characterize/isolate localization factors which recognize them and 3) examining the regulatory link between RNA localization and other post-transcriptional processes. Efforts also explore the role of key riboregulators (microRNAs) in several of these post-transcriptional processes. Our investigation will facilitate definition of the fundamental principals underlying the important process of mRNA trafficking and provide insights into the creation of cell polarity. Additionally, it will elucidate how the process can go awry, leading to developmental defects and disease. Recently, we identified the first human disease likely caused by RNA mislocalization. This opens a plethora of novel research avenues and created a second avenue of active lab research into human disease etiology and progression. In complimentary analyses, we are also embarking on a study to understand the molecular basis of pregnancy-induced autoimmunity with nerve and muscle targets. In both projects, our findings raise the possibility of totally new means of gene therapy.

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Jeffrey Gross
Molecular Biosciences Ph.D., Duke University http://www.bio.utexas.edu/research/grosslab/ Our research focuses on vertebrate eye development utilizing the zebrafish as a model system. Combining forward genetic screens with reverse genetic and embryological manipulations we hope to understand the molecular, cellular and developmental events that regulate eye formation and visual function. Current areas of interest in the lab include studies focusing on the development and maintenance of the lens and retinal pigment epithelium, elucidation of the molecular and cellular mechanisms that regulate morphogenesis of the eye as well as identification of the molecular components that function in generating positional asymmetries along the dorsal-ventral and nasal-temporal axes of the retina. Our research combines molecular, cellular, biochemical, transgenic and in vivo imaging techniques to address these questions. It is our hope that these studies will ultimately lead to a better understanding of visual system disorders such as macular degeneration, cataracts and ocular colobomas that often result in blindness in afflicted patients.

Robin Gutell
Integrative Biology Ph.D., University of California, Santa Cruz http://www.biosci.utexas.edu/IB/faculty/GUTELL.HTM The remarkable advances in Nucleic Acid sequencing and Computer technology is transforming Biology to a new level of understanding. We are now attempting to understand many biological and biochemical processes, and complex structures from a molecular sequence and molecular evolution perspective, utilizing computational biology and bioinformatics. Within this new frontier my lab is primarily interested in RNA structure and the evolution of these RNAs. The lab seeks an interdisciplinary group of people, with interests in RNA structure, Molecular Biology, Molecular Evolution, Computer Science, and Applied Mathematics. Currently we are addressing the following topics (1) STRUCTURE PREDICTION: RNA secondary and tertiary structure prediction with comparative sequence analysis. (2) PRINCIPLES OF RNA STRUCTURE: Relationships between RNA sequence and RNA higher order structure. (3) RNA FOLDING: transforming a single RNA sequence into its biologically correct higher order structure. (4) PHYLOGENETIC ANALYSIS: Inferring phylogenetic and evolutionary relationships from RNA structures. (5) WWW DATABASES: RNA sequence/structure web knowledgebase.

Marvin Hackert
Molecular Biosciences Ph.D., Iowa State University http://research.cm.utexas.edu/mhackert/ m.hackertj@mail.utexas.edu Our research focuses on understanding the function of proteins in relationship to their three-dimensional structures. Antizyme and antizyme inhibitor are regulatory proteins of ornithine decarboxylase that initiates polyamine biosynthesis. The structures of these proteins and their complexes are under investigation using x-ray crystallography, multidimensional NMR (with Dr. Hoffman), structural modeling, and other biophysical techniques. A collaborative project with Dr. Whitman involves the evolution of protein function and how a simple protein fold has been exploited to carry out a variety of different chemistries - tautomerization, decarboxylation and dehalogenation.

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R. Adron Harris
Neuroscience Ph.D., University of North Carolina http://www.utexas.edu/research/wcaar/harris/harris.html This laboratory is investigating molecular mechanisms responsible for alcoholism and drug dependence. We are defining actions of alcohol and other drugs on brain cells as well as the long-term changes in gene expression responsible for tolerance and dependence. The ion channels controlling neuronal excitability are of particular importance in our studies. Another aspect is the neurochemical basis for genetic differences in drug response. These experiments use genetically modified mice that vary in susceptibility to drug intoxication and dependence. A student working in this laboratory would carry out some of the following studies: (a) effects of drugs on ion channels; (b) site-directed mutagenesis of ion channels; (c) functional and structural studies of brain neurotransmitter receptors; (d) gene expression profiles of humans and mice using cDNA microarrays.

Rasika Harshey
Molecular Biosciences Ph.D., Indian Institute of Science http://www.sbs.utexas.edu/rasika/harsheylab/ We have two major research interests. (1) DNA-protein interactions in Mu transposition. Many cancer-causing retroviruses including HIV recombine with their host genomes in a manner similar to that used by transposable phage Mu. Assembly of a functional Mu transposase tetramer requires binding of the protein to Mu ends and also to a distantly located enhancer element. Several nucleoprotein complexes called transpososomes have been identified along the transposition pathway. Our current research goal is to understand the architechture of these transpososomes, why the enhancer remains associated with them until the completion of transposition, how target DNA is delivered to this complex, and what the similarities and differences are between the Mu and HIV integration systems. A combination of molecular genetics, biochemistry, and structural studies is being pursued. (2) Swarmer- cell differentiation in Salmonella typhimurium: a model for understanding surface signal transduction and pathogenesis. When this bacterium is propagated on a solid agar surface it differentiates into a specialized swarmer cell which is longer and has more flagella than a vegetative cell. Swarmer cells display a group surface motility that enables them to rapidly colonize the agar surface. The swarming colony lives within a biofilm. We have discovered that under these conditions, the well-known chemotaxis system is not required for chemotaxis, but rather for surface signal transduction. Microarray analysis is revealing interesting parallels between the biogenesis of flagella and that of needle-structures during swarming. Needle structures are distinct organelles that resemble flagella, but are specialized delivery vehicles for virulence proteins during infection of a host. Our experiments are aimed at understanding the molecular mechanism of this new pathway of signal transduction, investigating the similarities and differences between moving and adherent biofilms, as well using swarming as a model system for the analysis of virulence protein secretion.

Arjang Hassibi
Biomedical Engineering Ph.D., Stanford University http://www.cerc.utexas.edu/~arjang/ Our laboratory focuses on the system-level design of integrated sensors, biosensors, and bioelectronic systems. In particular, we are interested in the modeling, design, and validation of high-performance detection systems in biotechnology. Our ultimate goal is to not only improve the performance of existing platforms, but also introduce new sensing paradigms in a broad range of applications. To achieve this, we leverage our expertise in areas of analog and mixed signal integrated circuit (IC) design, sensor fabrication, stochastic modeling, technology computer-aided design (TCAD), and digital signal processing (DSP).new sensing paradigms in a broad range of applications. To achieve this, we leverage our expertise in areas of analog and mixed signal integrated circuit (IC) design, sensor fabrication, stochastic modeling, technology computer-aided design (TCAD), and digital signal processing (DSP).

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Christine Hawkes
Integrative Biology Ph.D., University of Pennsylvania http://www.biosci.utexas.edu/IB/faculty/hawkes/lab/default.html Research in the Hawkes Lab is focused on a mechanistic understanding of how plant-microbe interactions affect community and ecosystem processes. We explore how these relationships are influenced by alterations in climate, species invasions, and land use. This research is highly integrative and relies on a wide range of techniques, including DNA-based microbial community analyses, stable isotope biogeochemistry, and large-scale field manipulations.

David Hillis
Integrative Biology Ph.D., University of Kansas http://www.zo.utexas.edu/faculty/antisense/ Evolutionary biology provides a conceptual framework for understanding patterns of molecular diversity. For instance, phylogenetic analyses have permeated most fields of molecular biology in recent years, from studies of the epidemiology of human immunodeficiency viruses to studies of the origin of life. Work in my lab is divided into two main areas: empirical studies of molecular evolution and the development of evolutionary theory and methodology. The empirical studies include experimental manipulation of viruses to study evolution in vitro, phylogenetic analyses of highly conserved genes, and studies of molecular processes that give rise to new genes or maintain the structure of multigene families. The theoretical and methodological work is centered on finding the best ways to estimate phylogenies from molecular sequences and on simulations of molecular evolution using supercomputers.

David Hoffman
Molecular Biosciences Ph.D., Duke University http://hoffman.cm.utexas.edu/research/ Biophysical methods including nuclear magnetic resonance (NMR) spectroscopy and x-ray crystallography are extensively used in our investigations of protein and RNA structure and function. Current work includes the investigation of translation initiation factors, components of ribonuclease P, and proteins involved in the synthesis and regulation of polyamines.

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Hans Hofmann
Integrative Biology Ph.D., University of Leipzig http://cichlid.biosci.utexas.edu/ The research in Dr. Hofmanns laboratory seeks to understand the molecular and hormonal mechanisms that underlie social behavior and its evolution. African cichlid fishes are an ideal model system to address these questions because of their recent, repeated and rapid radiations that have resulted in hundreds of phenotypically diverse species. Our work uses a broad spectrum of approaches, ranging from ecological studies in the East African Great Lakes to functional genomics using custom-made cDNA microarrays for gene expression profiling in the brain. We also employ hormonal perturbations, neuroanatomical techniques and advanced microscopy, and bioinformatics tools. Although we have been working on a variety of topics in several model systems, current projects focus on two main areas: 1) Identifying genes that are involved in implementing social dominance and sex roles in the Tanganyikan mouthbrooder Astatotilapia burtoni; and 2) a comparative analysis of the ecological and molecular basis and evolution of divergent social organization (monogamy vs. polygamy) in a group of closely related (monophyletic) species, the Ectodini cichlids from Lake Tanganyika. By carefully and systematically querying the brains of these fish, we can use expression profiling to identify the molecular building blocks of complex behavior.

Jon Huibregtse
olecular Biosciences Ph.D., University of Michigan http://www.icmb.utexas.edu/cmb/directory/details.asp?id=1595 The Huibregtse lab studies the biochemistry of the ubiquitin proteolysis system, a major pathway for degradation of proteins in eukaryotic cells. Our interest in this pathway arose from study of human papillomaviruses (HPVs) and their association with uterine cervical carcinoma, the second leading cause of cancer-related deaths among women worldwide. Characterization of the HPV E6 protein showed that it promotes cellular immortalization by stimulating the ubiquitination and degradation of p53, an important tumor suppressor protein. This has led to insights not only into how HPV-infected cells escape normal growth regulation, but also to the identification of a class of ubiquitin ligases, known as HECT E3s. Current projects focus on understanding the biochemical mechanism and regulation of HECT E3s, in both mammalian and yeast cells, as well as the role of the HPV E6 oncoprotein in carcinogenesis. We are also studying the conjugation pathway for ISG15, a ubiquitin-like protein that becomes conjugated to a set of cellular proteins following activation of type I interferon pathways. The goal is to understand the function of ISG15 conjugation in anti-viral responses and the biochemical effect of ISG15 conjugation on target proteins.

Enamul Huq
Molecular Biosciences Ph.D., Purdue University http://www.sbs.utexas.edu/huq/lab Our research is aimed at understanding light signal transduction, specifically those pathways mediated by the phytochrome (phy) family of sensory photoreceptors that absorb light in the red and far-red region of the spectrum. The phy system, consisting of five members in Arabidopsis (phyA-phyE), controls almost every aspect of the plant life cycle including seed germination, de-etiolation and flowering time. To understand early phy signaling events, phy interacting factors, such as PIF1, have been isolated and characterized. PIF1 is a basic helix-loop-helix (bHLH) transcription factor that interacts strongly with the biologically active form of phyA and phyB. PIF1 overexpression and pif1 mutants showed defective seedling de-etiolation including, aberrant hypocotyl elongation and developmentally regulated loss of greening, suggesting that PIF1 is a key regulator of the phy-mediated control of seedling de-etiolation process. Future projects include investigating the molecular function of PIF1, identifying and functionally characterizing PIF1 interacting proteins and PIF1 target genes using biochemical, genetic and functional genomic approaches.

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Stephen Hursting
Human Ecology Ph.D., University of North Carolina http://www.utexas.edu/depts/he/ntr/hursting.htm Research Interests: Diet-gene interactions relevant to cancer prevention, particularly the molecular and hormonal mechanisms underlying energy balance-cancer associations. Focus Areas: 1. Mechanism-Based Nutrition and Cancer Prevention Studies in Genetically Engineered Mice. Our work has focused on developing and using genetically altered mouse models to identify preventive, particularly nutritional, approaches to offset the increased cancer risk due to a genetic lesion such as loss of p53 or APC tumor suppressor activity or overexpression of growth signaling molecules including Wnt-1 and insulin-like growth factor-1 (IGF-1). 2. Mechanisms Underlying the Energy Balance and Carcinogenesis Relationship: The Roles of IGF-1, Leptin and Inflammatory Pathways Obesity is an important risk factor for several human cancers, and the prevention of obesity via diet changes, physical activity, and pharmacologic interventions in animal models suppresses tumor development and extends lifespan. We are currently testing the hypothesis that the anticancer and antiaging effects of these interventions are mediated by reduced levels of IGF-1 leptin, and inflammatory factors. Using oligonucleotide microarrays and other molecular approaches, we are evaluating the molecular changes in response to dietary energy restriction with and without IGF-1 and/or leptin replacement. In addition, we are comparing other energy balance-modulating interventions, such as exercise, fasting, alcohol, phytochemicals, and a diet-induced obesity regimen to determine the key pathways linking energy balance and carcinogenesis. 3. Translational Nutrition and Chemoprevention Studies. We are collaborating with epidemiologists and clinical investigators to evaluate the effects of breast cancer chemopreventive agents including tamoxifen, raloxifene and aromatase inhibitors in combination with dietary or physical activity interventions in breast cancer clinical trials, and with several colleagues on preclinical studies of combinations of chemopreventive agents, dietary interventions and anticancer vaccines.

Brent Iverson
Chemistry Ph.D., California Institute of Technology http://research.cm.utexas.edu/biverson/ Antibody and enzyme engineering with an emphasis on creating better methods for improving protein function. Several new technologies have been developed and patented. Recent successes include (a) the production of improved antibodies capable of neutralizing toxins from pathogens such as anthrax and (b) altering the substrate specificity of an E. coli protease. These projects are carried out in collaboration with Dr. George Georgiou. Artificial macromolecules with defined higher order structure, including the first class of DNA threading polyintercalators and a unique molecular scaffold that folds into a novel pleated secondary structure. These projects examine large molecule structure and function from an organic chemistry perspective.

Vishwanath Iyer
Molecular Biosciences Ph.D., Harvard University http://www.iyerlab.org Nearly all cells respond to physiological or developmental cues by large-scale transcriptional reprogramming altering the expression of hundreds to thousands of genes throughout the genome. Such sweeping changes in gene expression also underlie diseases such as cancer, and they can also be caused by normal or abnormal genetic variation between individuals. Our lab is interested in understanding how gene expression is regulated across a eukaryotic genome. We focus on regulation not only at the level of transcription, but also post-transcriptional regulation mediated by miRNAs. We work in human cells and also use yeast as a model system to address various questions regarding global gene regulation. We use molecular and genomic experimental methods such as microarrays and next-generation sequencing, coupled with computational analyses. Broad research areas in the lab include i) transcriptional regulatory networks in yeast during stress responses, ii) role of chromatin structure and remodeling in transcriptional regulation, iii) regulatory networks during human cell proliferation, iv) regulation and function of miRNAs during proliferation, v) relationship of transcription regulation with genetic variability among individuals.

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Arlen W. Johnson
Molecular Biosciences Ph.D., Harvard University http://www.bio.utexas.edu/faculty/ajohnson/index.htm My lab studies ribosome export and mRNA degradation in yeast. We use techniques spanning genetics, cell biology, molecular biology, biochemistry and proteomics. Recently, we identified the nuclear export pathway for the large ribosomal subunit. This pathway depends on Crm1p, the receptor for leucine-rich nuclear export signals, and the 60S-binding protein Nmd3p that acts as an adapter for export. Current work involves characterization of the export complex, characterization of the nascent 60S subunit at different stages of nuclear export and regulation of the export pathway. Our work on mRNA degradation has focused on the enzymes responsible for 5 and 3-degradation. We have recently shown that inhibition of the 3-pathway by cis acting elements within an mRNA is sufficient for efficient translation of poly(A) minus mRNA in wild-type cells. Current work examines the biochemical function of the heterotrimeric Ski2/3/8 complex required for 3-decay and the functional and physical interaction of this decay system with other decay pathways and with the translation apparatus.

Kenneth Johnson
Molecular Biosciences Ph.D., University of Wisconsin http://research.cm.utexas.edu/kjohnson/ Three polymerases and a molecular motor: In projects related to AIDS, we examine HIV reverse transcriptase mechanism, its resistance to nucleoside analogs, and characterization of novel nonnucleoside inhibitors. In addition, we are studying the human mitochondrial DNA polymerase and have shown that toxic side effects of nucleoside analogs used to treat AIDS are a function of inhibition of mitochondrial DNA replication. We have also begun a new initiative to examine the RNA-dependent RNA polymerase of hepatitis C as a target for new drug development to combat the Hepatitis C virus. We also work on the mechanism of force production by the microtubuledependent motor protein, kinesin, by relating the structure of this dimeric protein to cooperative interactions necessary for coupled hand-over-hand motion. In each of these projects we combine novel fast kinetic techniques and single molecule studies with structural analysis to answer mechanistic questions.

Daniel Johnston
Neuroscience Ph.D., Duke University http://www.utexas.edu/neuroscience/Neuroscience/DanJohnston/ Research in my laboratory is primarily directed towards understanding the cellular and molecular mechanisms of synaptic integration and long-term synaptic plasticity. We have focused our attention on neurons and synapses in the hippocampus, an area of the brain that plays an important role in learning and memory. The hippocampus is also of interest because it has a low seizure threshold and plays an important function in human epilepsy. Our research uses quantitative electrophysiological, opticalimaging, and computer-modeling techniques. We are investigating the properties and mechanisms of long-term potentiation (LTP), a synaptic substrate for aspects of memory. This interest has led us to investigate not only the basic mechanisms of synaptic transmission but also the basic mechanisms of synaptic integration in the dendrites of the postsynaptic neuron. For example, we have recently used fluorescence imaging techniques and dendritic patch clamp recordings to identify the types and location of voltage-gated Na+, K+, and Ca+ channels in dendrites of hippocampal pyramidal neurons. Our computer- modeling studies, in which we attempt to reconstruct the biophysical properties of hippocampal neurons based on our experimental data, complement this work. Our studies of LTP have included investigations of the presynaptic or postsynaptic locus of change during LTP and the cellular mechanisms of induction. We hope that these investigations will enhance our understanding of the synaptic mechanisms of learning and memory and provide insight into the function of the hippocampus in the behaving animal.

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Christopher Jolly
Human Ecology Ph.D., Texas A&M University http://www.he.utexas.edu/ntr/jolly.php My lab focuses on understanding the biochemical/molecular mechanisms underlying reduced immune function in aging. We primarily focus on identifying signaling pathways which may lead to changes in lipid metabolism in T-lymphocytes. Specific examples include the cbl-mediated protein ubiquitination pathway and protein kinase C signaling in young and old rodent models. These studies employ the use of knockout mouse models in lipid metabolism and cbl-b signaling. Our main goal is to determine how these signaling pathways lead to age-dependent alterations in phospholipid metabolism. We recently have begun examining T-lymphocyte function in mitochondrial glycerol-3phosphate 1 knock out mice which we show have similar T-lymphocyte defects as seen in aged rodents. The lab is now examining T-lymphocyte development and effector function in this animal model using confocal microscopy and biochemical methods for lipid raft and immune synapse function. Ultimately, we hope to develop dietary and/or pharmacological strategies to delay or offset reduced immune function in the elderly.

Thomas Juenger
Integrative Biology Ph.D., University of Chicago https://webspace.utexas.edu/tjuenger/www/ My research focuses on the interface of ecological and evolutionary processes in natural plant populations. I am generally interested in phenotypic evolution, and have studied a number of systems over the course of my career. A current focus in the lab is the identification and characterization of genes underlying variation in drought adaptation among Arabidopsis thaliana ecotypes collected from around the world. This work is motivated by a desire to understand how climate and habitat variation have influenced the evolution of plant physiology. In addition, I have long-standing interests in the ecology and evolution of plant-animal interactions, including projects focused on pollination biology and herbivory in natural scarlet gilia (Ipomopsis aggregata) populations. A common theme of our work is the interplay of genetic and functional studies. Our approach usually couples quantitative genetic experiments [classic breeding designs & QTL/LD mapping], population genetic approaches, and selection analyses in studies of natural genetic variation. Ultimately, wed like to understand the forces shaping patterns of genetic variability in natural populations across a variety of selective regimes.

Adrian Keatinge-Clay
Molecular Biosciences Ph.D., University of California, San Francisco http://www.cm.utexas.edu/adrian_keatinge-clay Many important pharmaceuticals, including the antibiotic erythromycin and the immunosuppressant rapamycin, belong to a diverse class of molecules called polyketides. My lab uses protein crystallography and enzymology to study the molecular assembly lines that produce these natural products with the goal of accessing combinatorial polyketide libraries for use in the drug discovery process. Towards this end, we are determining the mechanisms by which polyketide synthase enzymes select small organic precursors, condense them, and set chiral centers during polyketide chain synthesis. Reprogramming these multi-enzyme complexes through genetic engineering is facilitated through advances in our understanding of modular polyketide synthase architecture.

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Sean Kerwin
Pharmacy (Medicinal Chemistry) Ph.D., University of California, Berkeley http://www.utexas.edu/pharmacy/divisions/medicinalchem/faculty/kerwins.html The long-term goal of our research is the development of selective strategies for the treatment of cancer and infectious diseases. We have focused on combining molecular recognition of disease cell-specific hosts with cytotoxic chemical warheads in order to design new compounds that are selectively toxic to the target cells. Our work takes place at the interface of computational chemistry, synthesis, biochemistry, and molecular biology. The target of current interest include certain nucleic acid sequences and their associated structures, such as G-quadruplexes and RNA hairpins, and particular nucleic acid processing enzymes that are implicated in cancer and infection. Structural and biochemical characterization of these targets enables us to use computational and combinatorial chemistry techniques to discover compounds that combine recognition of the targets with the desired biological effects.

Jonghwan Kim
Molecular Biosciences Ph.D., University of Texas at Austin Defining the molecular mechanisms maintaining stemness - self-renewal and pluripotency - of Embryonic stem (ES) cells, as well as induced pluripotent stem (iPS) cells is of great interest for understanding early development and for their potential therapeutic applications in regenerative medicine. Systematic understanding of the mechanisms controlling the stemness of pluripotent stem cells relies on high-throughput tools to define gene expression and regulatory networks at the genome level. Systems biology approaches have revealed highly interconnected ES cell specific regulatory networks in which multiple cis and trans regulatory elements are involved. Interestingly, recent studies have suggested that pluripotent stem cells and cancer cells share common features, notably self-renewal and a block in differentiation. Our laboratory studies transcriptional and epigenetic regulation of pluripotent stem cells using a broad panel of techniques including molecular biology and high-throughput genomics approaches in combination with computational analysis. Particularly, our research interests focus on understanding 1) regulatory networks controlling stemness of ES cells and iPS cells, and 2) regulatory networks generating common gene expression signatures between pluripotent stem cells and cancer.

Kimberly Kline
Human Ecology Ph.D., University of Texas at Austin http://www.utexas.edu/depts/he/ntr/kline.htm Research interests are in the interdisciplinary areas of nutrition and cancer biology. Long term goals are to better our understanding of the biological actions of vitamin E, both naturally occurring forms and synthetic derivatives. Current investigations involve understanding the role of a novel vitamin E analog referred to as alpha-TEA that reduces tumor burden and metastases of xenografts of human breast and ovarian cancers in Nu/Nu mice. Cellular, biochemical and molecular mechanisms of vitamin Es actions in inhibiting cell proliferation, inducing cellular differentiation, and triggering programmed cell death (apoptosis) are under study. Focus of these studies are on Fas/ Fas ligand and TGF-beta apoptotic signaling pathways that converge on JNK inducing mitochondria dependent and independent apoptotic pathways.

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Robert Krug
Molecular Biosciences Ph.D., Rockefeller University http://www.icmb.utexas.edu/research/krug The major focus of the Krug laboratory is the molecular biology of human influenza viruses (influenza A and B viruses), which cause widespread human disease. We are determining the molecular mechanisms of viral mRNA synthesis and viral RNA replication; and how the viral nonstructural proteins of these two influenza viruses contribute to pathogenesis and overcome host defense by inhibiting crucial cellular functions, including the 3 end processing system used for the production of cellular pre-mRNAs, and the interferon-induced modification of proteins by the ISG15 ubiquitin-like protein. Our research has already identified promising new targets for the development of antivirals, which are now the subject of high-throughput screens. In addition, research on influenza A viruses includes the analysis of the functions of the genes of H5N1 avian influenza viruses, which have the potential for causing the next pandemic.

Alan M. Lambowitz
Chemistry & Molecular Biosciences Ph.D., Yale University http://www.icmb.utexas.edu/research/lambowitz/ Our laboratory studies gene expression, RNA splicing, mobile self-splicing introns, and retroviral-like genetic elements in eukaryotes and prokaryotes. We are interested in mechanisms by which mobile introns integrate site-specifically into DNA, how proteins promote RNA folding and RNA catalysis, the mechanism and function of RNA helicases and their relationship to cancer, the evolution of introns and splicing mechanisms, and the evolution and origin of retroviruses and reverse transcription. Our research employs a combination of genetic, biochemical, molecular biological, and structural approaches. In practical applications of our work, we have used mobile group II introns to develop a new type of gene targeting vector, dubbed targetron, which can be programmed to insert efficiently into desired DNA sites. Targetrons are widely used for the genetic engineering and systems biology of diverse bacteria, and we are developing methods for using them in higher organisms, with potential applications in gene therapy. Our work on mobile group II introns led to the discovery of a new family of intron-encoded reverse transcriptase. We are studying these enzymes biochemically and structurally and have developed them as tools for applications in next-generation RNA sequencing, transcriptome profiling, analysis of RNA structure and RNA-protein interactions, and diagnostics. These novel reverse transcriptases open new approaches, which we are using in the lab for the discovery and profiling of miRNAs and other non-coding RNAs involved in important biological processes and human diseases.

Seongmin Lee
Pharmacy Ph.D., Purdue University http://www.seongminleelab.com The unifying theme of the Lee lab is the elucidation of molecular mechanisms underlying genome/epigenome management using toolkits of biochemistry, chemical and structural biology. In particular, we are interested in how DNA repair and epigenetic regulation maintain genomic and epigenomic integrity. Our current research interests include base-excision DNA repair, single-strand break DNA repair, and epigenetic regulation.

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Hung-wen (Ben) Liu

Pharmacy (Medicinal Chemistry), Chemistry / Biochemistry Ph.D., Columbia University http://uts.cc.utexas.edu/~liulab/ My group is currently working on three general areas with the focus aimed at the elucidation of the mechanisms of novel enzymatic reactions and the design of methods to control and/or regulate their functions. Most of the biological systems under investigation are target candidates for therapeutic drugs. Enzyme Mechanism and Inhibitor Design: We study the mechanisms of enzymes involved in diverse biological processes including the formation of bacterial cell wall, biosynthesis of and resistance to antibiotics, and biosynthesis and metabolism of lipids. Metabolic Pathway Engineering: Through selective disruption and/or substitution of sugar biosynthetic genes in the microorganisms that produce bioactive glycosylated secondary metabolites, we are exploring the feasibility of engineering natures biosynthetic machinery for the production of novel compounds carrying designed sugar appendages. Protein Function Regulation: We study poly(ADP-ribose) polymerase, an enzyme that recognizes damaged DNA and turns on the repairing machinery through polyADP-ribosylation of itself and other nuclear proteins. This posttranslational modification is also essential to other crucial cellular events including apoptosis.

Alan Lloyd
Molecular Biosciences Ph.D., Stanford University http://www.biosci.utexas.edu/MCDB/Lloyd.html The main goal of my lab is to understand plant developmental mechanisms and plant pigment pathways. In plants, the control of cell fate decisions is a central issue during plant development and pattern formation. One main focus of my lab is to use trichome (epidermal plant hair) initiation as a simple and amenable model to study the control of plant cell fate decision events. Over the years we have identified a combinatorial transcriptional complex that regulates trichome initiation and patterning. We are studying how this complex functions by manipulating the complex members and by investigating many of the complexs transcriptional targets. This complex also has pleiotropic control of the common red/purple anthocyanin pigment pathway in Arabidopsis and most other flowering plants. We have studied how the complex regulates these pigments and recently we have begun work on a red pigment pathway, the betalains, that are narrowly restricted to a single order of flowering plants that include beets, cactus and other taxa. The betalain pathway is much simpler than the anthocyanin pathway and has the potential to be used as a color and fluorescent marker in heterologous systems, fungi, animals and others.

Paul Macdonald
Molecular Biosciences Ph.D., Vanderbilt University http://flyworks.icmb.utexas.edu/ Regulation of gene expression at the post-transcriptional level has long been recognized for its essential role in early development, and has more recently emerged as a widespread phenomenon affecting the majority of mRNAs. We study several forms of control in a setting - Drosophila oogenesis - where this regulation is extensive and crucial for the patterning processes that define the body plan of the embryo. A combination of mRNA localization, translational regulation, and protein anchoring act to deploy several molecules at specific positions within the egg, where they act as localized determinants of cell fate. Our work on mRNA localization is focused on three mRNAs, bicoid, oskar and gurken, and has included the initial discovery of mRNA localization signals, and the ongoing identification of the factors that recognize the signals. Each of these mRNAs is also subject to translational control. Working primarily with the oskar mRNA we have identified two different forms of translational repression. One is mediated by the Bruno protein, which binds to a series of sites in the oskar mRNA 3 untranslated region. Current studies are aimed at understanding how Bruno mediates repression and how different Bruno binding sites function. The second form of repression prevents accumulation of Oskar protein from oskar mRNA on polysomes, a phenomenon that is strikingly similar to the repression of some mRNAs by microRNAs. We continue to explore this mechanism and its relationship to microRNA actions in the ovary.

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Dmitrii Makarov
Chemistry Ph.D., Institute of Chemical Physics, Moscow http://research.cm.utexas.edu/dmakarov/ Our work in single molecules theory is motivated by the recent developments in scanning tunneling microscopy, atomic force microscopy, and single molecule optical spectroscopy, which enable experimenters to observe and manipulate individual molecules. For example, by monitoring fluorescence, one photon at a time, from a dye molecule planted on a single protein, one can record a movie of the proteins dynamics. Understanding the information contained in such a movie requires theoretical insight into the relationship between the emission process and the molecules dynamics. Our research involves the development and use of simulation methods in order to study quantum dynamics of single molecules and to understand how these dynamics are manifested in the properties of the molecules emission. We use kinetic Monte Carlo methods to simulate the kinetics of protein and RNA folding and to understand the folding mechanisms of these molecules. We are also interested in the properties of denatured proteins and in the effects of confinement (e.g., inside the exit channel in a ribosome) on the mechanisms of folding. Some proteins have load-bearing functions in living organisms and are unique materials. We use atomistic simulations as well as simple theoretical models to study the mechanical resistance of individual protein molecules subject to stretching forces.

Edward Marcotte
Molecular Biosciences Ph.D., University of Texas at Austin http://polaris.icmb.utexas.edu Our research group combines experimental approaches with computational/bioinformatics approaches to study protein function and protein-protein interactions on a genome-wide scale. Weve discovered a number of features of genomes that allow us to predict functions for proteins that have never been experimentally characterized. Using these techniques and information from over 30 fully sequenced genomes, we were able to calculate the first genome-wide predictions of protein function, finding very preliminary function for over half the 2,500 uncharacterized genes of yeast. Now, with several hundred genomes in hand, were extending these techniques, as well as asking basic questions about the evolution of protein interactions and the evolution of genomes. Complementing the computational work, we are in the process of developing high-throughput technologies to measure gene function, such as NMR-based metabolic profiling, mass-spectrometry-based measurements of protein expression patterns, and high-throughput microscopy to measure cellular phenotypes in varying genetic backgrounds. From work of ours and others, it is apparent that proteins in the cell participate in extended protein interaction networks involving thousands of proteins, and we are interested in defining the accurate structure of the interaction networks and their dynamics over time and cell condition. In the long term, we would like to build a catalog of protein, mRNA and metabolite expression from cells grown under many different conditions, forming a quantitative picture of these molecular events inside cells. We expect that data of these sorts will put us on the road to developing predictive, rather than descriptive, theories of biology.

Mia Markey
Biomedical Engineering Ph.D., Duke University http://bmil.bme.utexas.edu/ The mission of the Biomedical Informatics Lab is to design cost-effective, computational medical decision aids that will help physicians better diagnose, treat, and manage cancer. Examples of current projects include computer-aided diagnosis of breast cancer from medical imaging exams (e.g., mammography), computational aids for decisions about breast cancer treatment that include quantitative measures of the expected changes to the survivors appearance, and computational methods for identifying biomarkers from genomic and proteomic analyses. All of our work is done in close collaboration with The University of Texas M. D. Anderson Cancer Center in order develop clinically relevant decision support systems.

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Michael Mauk
Neuroscience Ph.D., Stanford University http://www.clm.utexas.edu/mmlab/ We investigate information processing and learning in the cerebellum and prefrontal cortex. The levels of analysis are: 1) behavioral studies, reversible lesions and in vivo recordings of neural activity related to eyelid conditioning in the rabbit, 2) large-scale computer simulations of the cerebellum. Eyelid conditioning: The cerebellum contributes to our ability to make accurate movements through experience (motor learning). We study a tractable example of motor learning -- delay eyelid conditioning in rabbits and mice -- to study the mechanisms of this learning. We also use trace eyelid conditioning in rabbits to study learning in prefrontal cortex and to study interactions between prefrontal cortex and cerebellum. Computer simulations: The cerebellum is especially amenable to analysis using computer simulations, due to the relatively simple way it is engaged by motor learning and to its well known and simple synaptic organization. We use large-scale simulations designed to reflect as accurately as possible key properties of the cerebellum to 1) test hypotheses regarding network properties of the cerebellum, 2) identify key experiments, and 3) as an overall index of our understanding of cerebellar mechanisms of motor learning.

Jennifer Maynard
Chemical Engineering Ph.D., University of Texas at Austin http://www.che.utexas.edu/maynard/research/index.htm Building on decades of basic research in the biological sciences, fundamental principles underlying the function of complex biological systems are being elucidated in laboratories throughout the world. Concurrently, this understanding renders biology amenable to engineering approaches how can scientists control, predict and thus design novel biological systems? We use genetic engineering and biochemical techniques to address issues in immune system function and dis-function, with a view to correcting or augmenting this function. This work involves design of protein molecules, production in recombinant expression systems, biophysical and biochemical analysis and, ultimately, structural analysis to visualize the molecular basis of activity. Overall research goals: Control of cellular immunity through manipulation of T cell receptor interactions Define neutralizing epitopes in Bordetella pertussis and use this information to engineer more effective sub-unit vaccines Reverse engineer pathogenic strategies used by bacterial pathogens for biotechnological applications Apply protein engineering approaches to issues in structural biology.

Mona Mehdy
Molecular Biosciences Ph.D., University of California, San Diego http://www.biosci.utexas.edu/MCDB/mehdy.html Our research focuses on molecular mechanisms regulating gene expression during the defense response in plants to pathogen attack. Many stress responses, including the plant defense response, involve both transcriptional activation of specific genes and repression of the expression of other genes. We are defining mechanisms controlling the loss of selected mRNAs whose products appear to not contribute to resistance, using genetic, transgenic, and molecular approaches in the model plant, Arabidopsis, and in French bean. These studies have focused on cell wall protein genes and involve analysis of transcriptional repression and/or regulation of mRNA stability and the upstream signaling pathways. One major project concerns a redox-regulated RNA binding protein in French bean that is hypothesized to function in the rapid destabilization of a cell wall protein transcript. More broadly, this research will contribute to understanding regulation of mRNA stability.

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S. John Mihic
Neuroscience Ph.D., University of Toronto http://wcaar.icmb.utexas.edu/Mihic/mihic.htm Research in my laboratory is focused on characterizing the molecular mechanisms of action of alcohol, inhaled solvents, sedatives and anaesthetics on glycine, GABA-A and serotonin-3 receptors. We combine the techniques of receptor subunit mutagenesis with the electrophysiological characterization of receptors expressed by either cultured cells or Xenopus oocytes. Our studies are carried out using both whole-cell and single-channel electrophysiological recording techniques. We have identified specific amino acids of these receptors responsible for alcohol, inhalant and volatile anaesthetic enhancement of GABA-A and glycine receptor function. Current work in the lab is continuing the characterization of alcohol and anaesthetic actions on these receptors using single channel recording techniques. A second major research interest is the elucidation of the basic mechanisms of ion channel opening and receptor desensitization that occurs after neurotransmitter binding to its binding site. We have identified regions of these receptor subunits that influence channel opening and desensitization. Our recent work has shown that at least one form of receptor desensitization appears to occur as a direct consequence of channel opening and does not require the prior binding of neurotransmitter to its binding site.

Kyle Miller
Molecular Biosciences Ph.D., University College London DNA damage represents a formidable challenge to genome maintenance. To protect our genetic material, our cells have evolved multifaceted systems, collectively termed the DNA damage response (DDR), to detect and repair damaged DNA. It is clear that the true in vivo substrate of the DDR is not naked DNA but rather DNA assembled into chromatin. The structure and function of chromatin are regulated by histone modifications and chromatin modifying enzymes, which can markedly influence the DDR. Therefore, determining the interplay between the DDR and chromatin is fundamental for elucidating how cells maintain both epigenetic and genome integrity. The relevance of this research is highlighted by recent studies showing that mutations in many genes involved in the DDR and chromatin lead to cancer predisposition in humans. Therefore, we believe that deciphering the function of these pathways, both in normal and cancer cells, will contribute to the development of novel cancer therapies. Our research utilizes genetics, genomics, cell biology and molecular biology in both mouse and human tissue culture systems to gain insights into these areas of research. The lab also has interests in understanding anti-cancer drug mechanisms that function through DNA damage and chromatin. Many current drugs used in the clinic for cancer treatments act through DNA damage induction and pathways that regulate chromatin represent new targets for drug discovery. To explore this area of research, we employ a combination of chemical and molecular biology techniques to determine the in vivo interactions of small molecules (drugs) both at the cellular and molecular level. Taken together, the lab aims to engage in an active research program that applies a multifaceted and diverse approach to these questions in hopes of defining the relationship between chromatin and the DDR, as well as gaining insights into the mechanisms of cancer therapeutic drugs that act at the chromatin and DNA level.

Edward (Ted) Mills

Pharmacy Ph.D., Purdue University http://www.utexas.edu/pharmacy/divisions/pharmtox/faculty/mills.html The Mills lab is interested in the role of mitochondria in normal and pathologic processes pertaining to thermoregulation, metabolism, aging, and drug action. Research over the past several years has identified important novel mitochondrial regulatory functions in aspects of cell death, production of and signaling by reactive oxygen species, synaptic transmission and thermogenesis. The electron transport chain is the central component through which mitochondria regulate much of cellular physiology. As fuels such as fatty acids and sugars are combusted, electrons are donated to the respiratory chain protein complexes. As electrons travel along the series of complexes, protons are extruded from the inner (matrix) to the outer side of the inner mitochondrial membrane, forming a large proton gradient across the membrane that is quantitatively expressed as the mitochondrial membrane potential. Proton flux back into the matrix through the ATP synthase liberates energy that is consumed for the purpose of ATP production. Protons can also leak back into the matrix through uncoupling proteins, so named because they uncouple the proton gradient from ATP production. Protons flowing through uncoupling proteins also release energy, but since that energy is not consumed, it is released as heat. Recent findings from the Mills lab have linked thermogenic uncoupling to the lethal hyperthermic effects of the widely abused amphetamine drugs ecstasy and speed. Uncoupling proteins are expressed in humans, but their physiologic functions have not been defined. The approaches the Mills lab employs, including genetically modified strains of mice, C. elegans nematodes, and cultured cells, seek to define how uncoupling proteins work, and their roles in physiology, disease, and as targets of drug action.

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Tanya Paull
Molecular Biosciences Ph.D., University of California, Los Angeles http://www.biosci.utexas.edu/mgm/people/faculty/profiles/paull.htm Research in the lab is focused on the DNA damage response in eukaryotic cells, specifically the checkpoint activation and DNA repair responses that occur immediately after the introduction of chromosomal double-strand breaks. Several components of these DNA damage response systems have been implicated as tumor suppressors in mammalian organisms, thus establishing these factors as major targets in the progression from normal to unregulated cell growth. Current studies in the lab are primarily focused on the biochemical activities of a complex of proteins, Mrell/Rad50/Nbs1 (M/R/N), which are critical components in the repair of DNA double-strand breaks. We study the activities of recombinant M/R/N complexes in vitro to characterize its functions on different types of DNA substrates and recombination intermediates. In addition, in vivo assays in S. cerevisiae are utilized to identify functions of the complex and the effects of mutant complexes in cells. Our overall goal is to decipher the functions of each of these factors at a molecular level in order to understand how they cooperate to guard cells against genetic rearrangements and transformation.

Shelley Payne
Molecular Biosciences Ph.D., University of Texas Southwestern Medical Center http://www.sbs.utexas.edu/paynelab/ We are interested in the genetics and regulation of virulence factors of gram negative pathogens, including Shigella and Vibrio cholerae. Members of the Shigella species are found both extracellularly and intracellularly within the host, and distinct sets of genes are expressed in each of these environments. We are studying bacterial gene expression in vivo by a variety of molecular and microscopic techniques, and we have identified genes that are required for growth in the intracellular environment of the host. Bacterial genes found to be important for growth and survival in vivo include those that encode components of iron transport systems and those required for expression and localization of cell surface proteins.

Steven Phelps
Integrative Biology Ph.D., University of Texas at Austin http://www.biosci.utexas.edu/ib/faculty/phelps.html The lab employs a diverse array of approaches, ranging from computational models to the molecular analysis of gene expression. This work is strongly anchored in empirical studies of animal behavior in both the laboratory and field. Using exotic rodent models, we focus on the nature and consequences of within- and betweenspecies variation in neuronal gene expression and behavior. For example, we study how individual differences in the neuronal distribution of vasopressin receptors contribute to social attachment, space-use and sexual fidelity in the socially monogamous prairie vole. Another major model concerns the production and perception of advertisement songs in the singing mouse -- a project that includes neuroanatomical studies, field playbacks, and population genetic analysis of song variation. These projects involve substantial field components in both the U.S. and Central America.

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Jonathan Pierce-Shimomura
Neuroscience Ph.D., University of Oregon http://www.utexas.edu/neuroscience/Neuroscience/JonPierce-Shimomura/ Our lab seeks to identify genetic mechanisms that govern behaviors. We approach this complex subject by studying how conserved genes contribute to behaviors in the simple but powerful model nematode C. elegans. We are currently focused on two issues: 1) How the worm switches between distinct forms of rhythmic locomotion : crawling and swimming. Understanding the genes and neural mechanisms that enable this switch has implications for explaining how all nervous systems switch between rhythmic activities such as normal and gasping patterns of respiration, walking and running gaits, and even different rhythms in the hippocampus for processing ofmemory. 2) How the worm responds to different drugs such as ethanol and anesthetics. The molecular mechanisms that underlie the in vivo effects for many drugs of benefit and abuse are often unclear in vertebrate systems. By using the worm as a minimal system, we can rapidly identify which uncharacterized and novel molecules are responsible for behavioral responses to drugs. To study the genetic basis of behaviors, we combine genetic screens to identify genes involved in a behavior, in vivo electrophysiology and calcium imaging to study the function of identified neurons in the behavior, and image analysis tools to quantify the behavior.

Martin Poenie
Molecular Biosciences Ph.D., Stanford University http://www.biosci.utexas.edu/MCDB/poenie.html We are interested in the cell biology of T cells and how they carry out their effector functions. In particular we are want to know how signaling events lead to reorganization of the T cell cytoskeleton and translocation of the microtubule organizing center (MTOC) to the site where T cells make contact with an antigenic target cell. This contact site is remodeled into a specialized junction known as the immunological synapse due to signals that are generated when a T cell makes contact with its target. As part of this remodeling event dynein, a microtubule motor protein, becomes anchored at the synapse. Dynein then serves to pull microtubules and the MTOC towards the synapse. Recently we developed modulated polarization microscopy, an instrument that allows us to visualize the cytoskeleton in real time. We have used this instrument together with three dimensional immunofluorescence microscopy to show how microtubules associate with the synapse. Our current effort is to understand how T cell signaling causes a complex of proteins that include dynein to relocate to the synapse.

William Press
Computer Sciences and Integrative Biology Ph.D., California Institute of Technology http://www.nr.com/whp/ My work is in computational biology, especially whole-genome studies. My collaborators and I develop and test new algorithms for finding and characterizing functional sequence, and for understanding evolutionary pressures affecting whole genomes. I am also interested in biostatistics, especially data mining on large experimental data sets, and in computational algorithms generally.

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Nicholas Priebe
Neuroscience Ph.D., University of California, San Francisco http://w3.biosci.utexas.edu/priebe/labsite/Home.html The massive expansion of cerebral cortex is a hallmark of the human brain. We know that the cortex plays an essential role in our perceptions and actions. Sensory inputs from the periphery are transformed in the cortex, allowing us to generate appropriate motor outputs. My lab studies the cortical circuitry and the computations that underlie such transformations, using vision as a model system. In visual cortex, neuronal circuitry performs the computations that extract motion, orientation and depth information about the visual environment from subcortical inputs. For example, primary visual cortex (V1) is the cortical location in which information from the two eyes is first integrated, ultimately allowing us to perceive depth in our visual field. By understanding the circuitry that underlies these kinds of computations, we gain insight into similar computations that occur throughout cortex.

Kimberly Raab-Graham
Neuroscience Ph.D., University of California, Santa Barbara http://www.utexas.edu/neuroscience/Neuroscience/KimberlyRaab-Graham/ My current research has focused on identifying synaptic mRNAs and developing tools to characterize the local translation of these transcripts. I now plan to use these tools to address the questions of what mRNAs are locally translated in response to neuronal activity, what are the signaling pathways that are necessary and sufficient for local translation and local insertion into the membrane, and finally how mRNAs are targeted to the appropriate subcellular location. Since information processing by a neuron is dependent on the number and distribution of ion channels and receptors on the plasma membrane, it is of great interest to identify the molecular mechanisms that alter the current density or affect the targeting of a protein. These experiments will yield insight into the normal and/or dysfunctional communication within neuronal networks in the brain.

Pengyu Ren
Biomedical Engineering Ph.D., University of Cincinnati http://biomol.bme.utexas.edu/lab/ Dr. Ren studies the structure and function of biomolecules, with pharmaceutical and biomedical applications. Rens research team uses a range of computational tools to study the structure, dynamics and interactions of proteins, nucleic acids and other macromolecules, and to search for compounds mimicing and interfering with biomolecues for diagnostic and therapeutic purposes. Ren is developing a multi-scale modeling technique that allows scientists to efficiently study bimolecular assemblies.

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John Richburg
Pharmacy Ph.D., Rutgers http://www.utexas.edu/pharmacy/divisions/pharmtox/faculty/richburg/lab.html The broad focus of my research is the investigation of the mechanism(s) by which environmental toxicants affect male reproduction. My specific research interests are directed towards thee understanding of the signaling pathways that regulate germ cell death via apoptosis in the testis and how environmental toxicants can disrupt this process to result in disease. Apoptosis, or programmed cell death occurs in the testis normally as a physiologic mechanism to limit the number of germ cells in the seminiferous epithelium. Recent evidence suggests that exposure to chemicals found in the environment may play a role in male infertility and the pathogenesis of testicular cancer. However, despite the association of exposure to these agents and infertility, little is known of the mechanisms by which they act on the male reproductive system. Current projects in the lab are centered on revealing paracrine-signaling systems responsible for toxicant-induced germ cell death via apoptosis. Our current focus is on understanding the role of the death receptors (e.g., Fas/ DR3, 4, 5 & 6) and their ligands in the testis. Current experimental approaches include: confocal microscopy, laser capture microdissection, northern and western blot analysis, RT-PCR, in situ hybridization and immunohistochemistry. The ultimate goal of this research is to define the final common mechanism(s) of toxicant-induced germ cell death and provide insights into the role that environmental toxicant exposures play in male infertility and testicular cancer.

Jon Robertus
Molecular Biosciences Ph.D., University of California, San Diego http://research.cm.utexas.edu/jrobertus/ Research in my laboratory focuses on protein structure, action, engineering and rational drug design. This includes analysis of three-dimensional structure by X-ray crystallography and site-directed mutation of cloned genes. These methods are applied to a number of systems. The plant derived toxin ricin is a potential biowarfare agent; we are designing antidotes to it using structure-based methods. Other projects include analysis of of the translin/trax system for mRNA silencing and trafficking, anti-fungal drug design against Met synthase, and analysis of the MobA protein for the interspicies transmission of drug resistance.

Stanley Roux
Molecular Biosciences Ph.D., Yale University http://www.sbs.utexas.edu/roux/ We are studying how the stimuli of light and gravity alter patterns of plant development. In our studies of light-induced responses we have found that ectoapyrase, an enzyme regulated by the photoreceptor phytochrome, can modulate the levels of extracellular ATP [eATP], and that, surprisingly, changes in [eATP] can influence toxin resistance, hormone transport, pollen germination, wound responses, and gravitational growth in plants. This indicates that eATP, which is a physiological regulator in animals, also influences plant growth and development, and we are investigating how this happens. For our gravitational studies we are using two model systems, Arabidopsis and spores of the fern Ceratopteris. In Arabidopsis we are using genetic approaches to evaluate the role of annexins, which mediate the secretion of wall materials to growing points of cells, in gravitropic growth. In Ceratopteris spores, where gravity directs polarity development, we are using microarrays to compare the pattern of gene expression in space-flown vs. earth-grown cells, so as to identify genes needed for early stages of the spores graviresponse.

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Rick Russell
Molecular Biosciences Ph.D., Johns Hopkins University http://research.cm.utexas.edu/rrussell/ Our group combines biochemical and biophysical approaches to study the processes of RNA folding and assembly with proteins. Some of natures most complex and important enzyme machines are composed of RNA and protein. For these machines to function, each RNA and protein component must fold to its correct three-dimensional structure and all must assemble into a macromolecular complex. The goal of our research is to obtain a quantitative and rigorous molecular understanding of the processes and principles that govern RNA folding and assembly with proteins. We are also interested in RNA chaperones, proteins that are not required for function of the final complex but assist in RNA folding. The approaches used in the lab range from monitoring enzyme activity, which can be a powerful and specific probe for formation of a native structure, to single molecule fluorescence, which allows sensitive detection and characterization of folding and assembly intermediates.

Bob Sanders
Molecular Biosciences Ph.D., Pennsylvania State University http://www.biosci.utexas.edu/mgm/people/faculty/profiles/sanders.htm Research interests are in the interdisciplinary areas of nutrition and cancer biology. Long term goals are to develop vitamin E analogs as anticancer agents, and to increase the understanding of the biological actions of vitamin E, both naturally occurring forms and synthetic analogs. Current investigations involve conducting chemotherapeutic studies with a vitamin E analog referred to as alpha-TEA, using syngeneic and xenograft preclinical animal models. Cell and molecular studies are focused on understanding how alpha-TEA restores death signaling and blocks pro-survival signaling in human breast, prostate and ovarian cancer cells using both cell culture systems and animal models.

Sara Sawyer
Molecular Biosciences Ph.D., Cornell University http://web.biosci.utexas.edu/sawyer Evolutionary changes driven by historical viral epidemics have left a molecular fossil record in our DNA sequence. Our goal is to learn about natural strategies that have been successful at beating viruses in the past, and how these might be exploited in the fight against modern viral attacks. We are using a broad array of techniques from molecular evolution, virology, experimental evolution, and comparative genomics to look at human and primate genes that encode inhibitors of viral infection. We are also exploring evolutionary trade-offs, where human genes change enough to avoid susceptibility to new viruses, yet still maintain their ability to perform other important cellular functions. We are interested in the inverse effects that evolutionary change can have on multiple, intertwined biological systems.

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David Stein
Molecular Biosciences Ph.D., Stanford University http://www.biosci.utexas.edu/MCDB/Stein.html Most of the research in our lab is focused on the question of how a complex multicellular organism develops from a seemingly simple single cell, the fertilized Drosophila egg. In one set of investigations, we are studying how embryonic dorsal-ventral polarity is established. The polarity of the embryonic dorsal-ventral axis is defined by a ventrally-produced extracellular ligand which binds to and activates Toll, a receptor protein present in the membrane of the embryo. This mechanism is very similar to one which controls the formation of the anterior and posterior termini of the Drosophila embryo. In that process, an extracellular ligand formed specifically at the two ends of the embryo activates Torso, another receptor protein localized to the embryonic membrane. Experiments in our lab are aimed at understanding at the molecular level how the localized production of these receptor ligands is accomplished and defines embryonic pattern along the dorsal-ventral axis and at the embryonic termini.

Scott Stevens
Molecular Biosciences Ph.D., University of North Carolina http://www.biosci.utexas.edu/mgm/People/Faculty/profiles/stevens.htm Ribonucleoproteins (RNPs) function in many cellular processes and the malfunction of some of these RNPs cause serious human disease. To better understand how disease states can be corrected, our laboratory studies the ways in which RNA and protein assemble into large RNP complexes, how those complexes function, how they are rearranged in the course of their action and how they get put back together again. Using yeast genetics, biochemistry, cryo-electron microscopy and X-ray crystallography, we seek to understand the details of the structure and function of the yeast spliceosome and other RNPs. We are also experimenting in the mammalian system by designing human cells and mice to allow us to study the complex splicing reaction in these model systems as well.

Laura Suggs
Biomedical Engineering Ph.D., Rice University http://www.bme.utexas.edu/research/suggs/index.html Our lab is primarily interested in the development of biologically active materials and their use and behavior in cardiovascular tissue engineering. It is important to understand molecular and cellular mechanisms during processes such as vasculogenesis as well as the structure of both natural and synthetic polymers and their effect on living tissues. With this fundamental knowledge base, biomaterials can be designed to mimic naturally occurring structures found in the supporting extracellular matrix. We utilize a number of techniques including polymer synthesis and characterization using traditional wet chemistry techniques as well as various biochemical analysis techniques. We culture bone marrow stem cells and evaluate differentiated phenotype and function using immunohistochemistry and PCR. Our lab is also working on developing in vitro models of vascularization based on coronary vessel development during embryogenesis.

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Carla Van Den Berg

Pharmacy PharmD., University of Texas Health Science Center at San Antonio & The University of Texas at Austin http://www.utexas.edu/pharmacy/divisions/pharmtox/faculty/vandenberg.html My lab studies the importance of growth factor signaling in both breast cancer progression and resistance to chemotherapy treatment. We have specifically focused on the Insulin-like Growth Factor-I Receptor (IGF-IR) signaling pathway since it is often up-regulated in breast cancer and conveys a pro-survival and mitogenic response to breast cancer cells. We also study the intracellular kinase JNK (c-Jun N-terminal kinase). JNK is an important mediator of cellular response to a variety of environmental cues. We use a wide variety of techniques in my laboratory to evaluate mammary tumor cell biology and mammary gland function. These tools and techniques include transgenic and knockout mouse models and cell lines, organotypic (3D) cell culture, flow cytometry, protein analysis, fluorescent microscopy, gene transfection and gene knockdown approaches to determine the functions of various signaling molecules. These techniques are used to evaluate phenotypes including tumorigenesis, metastasis, cellular migration, invasion, proliferation, and death.

Karen Vasquez
Pharmacy Ph.D., Baylor College of Medicine http://www.utexas.edu/labs/vasquez/ Our research efforts are focused in three general areas within an overall theme of genome instability, DNA damage and mechanisms of repair. A unique feature of our approach is an emphasis on the role of DNA structure, including non-canonical structures such as triplex DNA, as recognition sites for repair machinery, sources of genomic instability, and as a basis for technology to target DNA damage to specific genomic sites. 1. DNA structure in genomic instability and human disease. The consequences of genomic instability are causative factors for several human diseases that involve repetitive DNA sequences. Many repetitive sequences are able to adopt non-B secondary structures. Interestingly, many of these repeats occur near breakpoints of chromosomal translocations, implicating them in cancer etiology. Our studies will determine the mutagenic potential and mechanistic role of non-canonical DNA structures in human disease, with an emphasis on translocation-mediated cancers. 2. Molecular mechanisms of DNA damage recognition and repair. Defects in DNA repair systems can lead to severe clinical disorders; for example, it is estimated that ~90% of human cancers result from improperly repaired DNA damage. Our work aims to elucidate the molecular basis of damage recognition in order to develop a better understanding of the mutagenic potential and cancer risks of different types of DNA lesions. 3. Novel strategies to modify gene structure and function in living organisms. An area of intense investigation in my laboratory is the development of triplex technology to improve the existing gene targeting methods by directing damage to specific genomic sites to increase the frequency of recombination and to direct gene inactivation. Our objective is to improve the utility of triplex technology as a tool for genetic manipulation in animals and to develop novel therapeutic strategies for treating cancer.

Steven Vokes
Molecular Biosciences Ph.D., University of Texas at Austin http://www.sbs.utexas.edu/vokes_lab/ Transcriptional and cis-regulatory mechanisms underlie the process of cellular specification during embryonic development. Here, initiating signals tell undifferentiated cells their fates and positions within an organ. In many cases these initiating signals are known, but it is not understood how these signals are integrated into a quantitative transcriptional output that is interpreted by the cells. We seek to understand how cells take stock of all of the inductive signals they receive from their neighbors and translate this into a genetic network that specifies their fate and position. We employ a combination of genetic, molecular and genomic approaches using the mouse limb bud as a model system. We recently completed a whole genome characterization of the transcription factor binding sites underlying Sonic hedgehog mediated patterning in the limb and are in the process of applying this information to understand the regulatory processes that confer shape and size dimensionality to the limbs and digits.

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James Walker
Molecular Biosciences Ph.D., University of Texas at Austin http://www.biosci.utexas.edu/mgm/people/faculty/profiles/walker.htm My research interests include the mechanism by which the bacterial chromosome is replicated, how replication is controlled, and how replication is integrated with cell division. Specifically, we study components of the Escherichia coli replicative polymerase, DNA polymerase III, the specific functions of some of the subunits of this tenprotein complex, and how the genes which encode these subunits are expressed and regulated. Also under study is the mechanism by which a critical activator protein initiates replication at the unique replication origin once and only once in each cell cycle and always at the same time in the cell cycle. E. coli was chosen as a model for replication in higher organisms because the mechanisms are thought to be very similar, but work with E coli provides the advantage of superior technology and genetic analysis. We are interested also in the structure and developmental biology of long, ribbon-like appendages attached to Clostridium spores.

John Wallingford
Molecular Biosciences Ph.D., University of Texas at Austin http://www.bio.utexas.edu/faculty/wallingford/index.html The process by which embryos acquire their final shape involves the coordination of cell fate decisions with cell movement. We are taking an integrated approach to understanding this process in vertebrate embryos. We combine molecular manipulations, time-lapse imaging, and old-fashioned cut & paste embryology to investigate molecular signaling, individual cell behavior, and tissue rearrangement. By considering all of these components and how they affect the final body plan, we hope to build a comprehensive picture of early embryonic morphogenesis.

Tandy Warnow
Computer Science Ph.D., University of California, Berkeley http://www.cs.utexas.edu/users/tandy Phylogenies (i.e. evolutionary trees) are fundamental to our understanding of evolution, and their inference is a major part of research in many areas of biology. With the production of increasing amounts of biomolecular sequence data, we are reaching a moment where the bottleneck in phylogenetics is not the quantity of data, but its analysis. The most frequently used techniques for reconstructing trees from biomolecular sequence data attempt to solve essentially intractable problems. The result of such a phylogenetic analysis is usually not a single optimal tree, but rather the set of all the best trees found during the search. My recent work focuses on four major questions, all related to computational problems in evolutionary tree reconstruction: (1) The analytical study of convergence rates of different methods, and the development of provably fast-converging methods. (2) Fast techniques for NP-hard optimization problems, such as maximum likelihood and maximum parsimony. (3) The inference of complex evolutionary histories. In this area, I have focused on the inference of evolution from whole genomes, and the detection and inference of reticulate evolution. (4) Data mining on the set of trees obtained during a phylogenetic analysis. In addition to my work in computational and statistical aspects of biological phylogenetics, I also work on comparable problems in historical linguistics, which is the inference of evolution for languages.

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Lauren Webb
Chemistry Ph.D., California Institute of Technology http://www.icmb.utexas.edu/cmb/directory/details.asp?id=3837 Research in the Webb group seeks to understand and manipulate the mechanisms of interaction, organization, and self-assembly of biological macromolecules that lead to the complex and emergent properties of living systems. Macromolecular interactions in biological systems are now a major focus of interest. In the post-genomic era, enhanced understanding of the cooperation between biological molecules such as proteins, DNA, RNA, and lipids is necessary to explore the complexity of living cells. Macromolecular interactions lead to emergent properties necessary for life, but can only be studied or understood if the molecular-level details that drive and control those interactions are themselves understood. Furthermore, molecules that promote or disrupt specific macromolecular interactions have vast pharmacological potential. The affinity and specificity of macromolecular interactions are the result of both structural and electrostatic driving forces, but while the field of structural biology has made great advances, much less is understood about electrostatic influences. The Webb group measures electrostatic fields at protein-protein interfaces and seeks to develop computational models that accurately predict these interactions. We do this using vibrational Stark effect (VSE) spectroscopy, in which spectral shifts of a probe oscillators energy is related directly to that probes local electrostatic environment.

Marvin Whiteley
Molecular Biosciences Ph.D., University of Iowa http://www.icmb.utexas.edu/cmb/directory/details.asp?id=2858 Bacteria exhibit many social activities and represent a model for dissecting social behavior at the genetic level (recently defined as sociomicrobiology). One example of social behavior in bacteria is the use of small molecules to communicate within a bacterial population, a process referred to as quorum sensing. Recent work has provided evidence that quorum sensing allows bacteria to amass a coordinated response in a density-dependent manner to accomplish tasks which would be difficult to achieve for a single bacterium. Although much is understood about the molecules used for communication, little is known about how these molecules are trafficked within a bacterial population or how these molecules are perceived by individual bacterial cells. My laboratory is interested in understanding the mechanism of signal trafficking between bacterial cells and how these signals are perceived by individual cells. We currently use two pathogenic bacteria, Pseudomonas aeruginosa and Actinobacillus actinomycetemcomitans and a plant commensal Sinorhizobium meliloti to study signal trafficking and perception between bacterial cells and between bacteria and eukaryotic cells. Recent evidence in our laboratory indicates that some bacteria package signals into membrane vesicles that facilitate delivery of these molecules to other cells within the population. The overall goal of my lab is to understand signal trafficking and perception at the molecular level as well as provide an ecological role for these communication systems in the natural environment.

Christian Whitman
Pharmacy (Medicinal Chemistry) Ph.D., University of California, San Francisco http://www.utexas.edu/pharmacy/divisions/medicinalchem/faculty/whitman.html My laboratory is interested in how enzymes evolve and how they work. We are studying two groups of enzymes, the tautomerase superfamily and the fumaryl acetoacetate hydrolase (FAH) superfamily. Both superfamilies likely evolved from common ancestors through divergent evolution. The members of the tautomerase superfamily use a conserved amino-terminal proline and an arginine to catalyze diverse reactions including tautomerization, dehalogenation, hydration, and decarboxylation. The FAH superfamily members use an enzyme-bound metal ion to catalyze hydrolysis, decarboxylation, and perhaps hydration reactions. Using a variety of mechanistic and structural techniques, we examine a range of reactions in these two groups so we can understand the principles used by Nature to make new enzymes from old ones. Understanding this process will enable us to design novel biocatalysts through rational design or directed evolution. This knowledge also has implications for the evolution of enzymes that degrade antibiotics (leading to antibiotic-resistant bacteria) and environmental pollutants

Claus Wilke
Integrative Biology Ph.D., Ruhr-Universitt Bochum http://www.biosci.utexas.edu/IB/faculty/WILKE.HTM Wilke works in the areas of computational and theoretical biology. His research can be broadly subdivided into three areas: (1) molecular evolution, (2) evolution of RNA viruses, (3) theoretical population genetics. 1. One of the major open questions in molecular evolution is to identify the dominant constraints that shape protein evolution. Recent evidence indicates that selection for adequate protein expression and folding may play a more important role in shaping evolutionary rates than selection for protein function. Wilke is studying how point mutations and recombination affect protein folding, how a proteins structure affects its evolutionary rate, and more generally is working towards a theory of protein evolution firmly grounded in protein biochemistry. 2. RNA viruses (such as influenza virus or human immunodeficiency virus) tend to have high mutation rates, and evolve rapidly in reaction to immune response or treatment. Frequently, they adapt to new hosts, and the majority of newly emerging infectious diseases are RNA viruses that cross the species barrier from animal host to human (examples are SARS or the avian influenza). However, a high mutation rate also implies frequent deleterious mutations. Wilke is studying questions such as how RNA viruses can thrive under high rates of deleterious mutations, how they can mask the effect of deleterious mutations under coinfection, and how they adapt to changing hosts. 3. The origins of theoretical population genetics date back to the early 20th century, and today the basic theory of population genetics is well understood. Nevertheless, many open questions remain. Wilke is working mainly on the speed of adaptation in asexual populations, on neutral evolution, and on population dynamics in time-dependent environments.

Casey Wright
Pharmacy Ph.D., Kansas State University http://www.utexas.edu/pharmacy/divisions/pharmtox/faculty/wright.html My laboratory is focused on unraveling the complex regulatory mechanisms that govern the activity of the pleiotropic transcription factor nuclear factor-kB (NF-kB), with the long-term goal of identifying pharmacological intervention points along the NF-kB signaling module. Because of the numerous genes that NF-kB transactivates, particularly those that encode pro-inflammatory, pro-survival and pro-cell cycle proteins, the link between deregulated NF-kB activity and disease has become increasingly evident. For instance, the sustained activation of NF-kB can lead to increased expression of numerous pro-inflammatory cytokines and ultimately to chronic inflammation, which promotes the development and progression of cancer. In addition to the promotion of tumorigenesis, deregulation of NF-kB contributes to autoimmune and inflammatory diseases, including ulcerative colitis and rheumatoid arthritis. NF-kB is composed of five different subunits, c-Rel, RelA (p65), RelB, p50/p105 (NF-kB1) and p52/p100 (NF-kB2), that homo- or heterodimerize to form functional transactivating complexes. We have uncovered a mechanism of tumor necrosis factor receptor (TNFR)-dependent NF-kB activation that is regulated by the aryl hydrocarbon nuclear translocator (ARNT; also known as hypoxia-inducible factor 1-beta). ARNT is a transcription factor that is integral in the regulation of xenobiotic and hypoxic responses but had not been previously shown as a component of NF-kB signaling. Our current focus is whether NF-kB regulation via ARNT is disrupted during exposure to xenobiotics, such as dioxin, which might result in altered NF-kB activity and in turn reveal possible links between toxicant exposure and tumorigenesis. Other interests in the laboratory include investigations of the NF-kB p52/p100 subunit as a suppressor of cell-cycle inhibitory genes and characterizing novel TNFR-interacting proteins that function at the level of the plasma membrane to activate NF-kB..

Harold Zakon
Neuroscience Ph.D., Cornell University http://www.utexas.edu/neuroscience/Neuroscience/HaroldZakon/research.html Ion channels are fundamental for the workings of the nervous system. We study the function, regulation, and evolution of voltage-dependent ion channels. Our main focus has been to study the regulation of sodium and potassium channels by hormones such as testosterone, estrogen, and by phosphorylation. A major emphasis of the laboratory has been cloning these ion channel genes and understanding their transcriptional regulation. In addition, we have been studying the molecular evolution of ion channel genes in vertebrates.

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Boris Zemelman
Neuroscience Ph.D., Stanford University We strive to understand the role of hippocampus in memory formation by manipulating its functional elements, namely the assemblies of cells that carry out particular tasks. This objective raises four practical questions. How are such assemblies to be defined? How can they be accessed? How might their activity be perturbed? And how should the resulting change in the system be detected and evaluated? Hippocampal neurons are organized into three broad classes: excitatory, inhibitory and modulatory. In some cases, the classes can be subdivided further, on the basis of neurochemical markers mainly calcium binding proteins and neurotransmitters. We work in mice, using these differences in the complement of expressed proteins to target specific cell populations. As an alternative, we are testing several new genetic approaches designed to identify and access neurons displaying heightened activity during memory tasks. Selected neurons are sensitized to subsequent manipulation using a variety of heterologous receptors and ion channels. We then evaluate the effects of cell-type specific optical or pharmacological perturbation on hippocampal circuit dynamics (electrophysiologically) and on animals memory functions (using behavioral assays)..

Xiaojing (John) Zhang

Biomedical Engineering Ph.D., Stanford University http://www.bme.utexas.edu/research/zhang/ Our current research focus is on the development of miniature tools with which to describe cellular processes quantitatively. Using these novel cell-machine interfaces, we can investigate, with extremely high spatial-temporal resolution, the impact of both genetic variation and microenvironmental perturbation can be investigated on intra-cellular biochemical signaling pathways, cell mechanics and the robustness of development networks. In particular, we are integrating live imaging functionalities and photonics based cell manipulations with microelectromechanical systems (MEMS), microfluidics and nanotechnology to understand the regulation of gene expression under controlled perturbations. We are developing a uniquely integrated sub-cellular scale surgery, force sensing and in vivo microscopy technology that are broadly applicable across a wide range of molecular dynamics studies in live cells and embryos. The techniques capabilities will be demonstrated by studying the dynamic structure-function relationship of live cells and embryos as it responses to local environmental perturbation. A combination of genetic regulation and microenvironmental perturbation might prove especially useful for identifying the fundamental mechanisms responsible for development biology and critical bio-chemical networks. This could transform our understanding of genomics, proteomics, and drug discovery and lead to personalized drugs and molecular diagnostics, resulting in both more efficient medical practice and improved healthcare.

Yan Jessie Zhang

Molecular Biosciences Ph.D., The Scripps Research Institute http://zhang.cm.utexas.edu/ A major focus of Zhangs research is the elucidation of the fundamental principles of transcriptional regulation. The primary experimental approaches used in the laboratory are macromolecular structure determination and allied biophysical techniques. The transcription of DNA information into mature RNA messages requires a temporally changing transcription apparatus, which is assembled from RNA polymerase II and various processing factors. The appropriate assembly of the transcription apparatus is governed by information programmed in the C-terminal domain (CTD) of RNA polymerase II. This so-called CTD code operates through changes in the conformation of CTD, which are effected largely through alteration of the phosphorylation state of this domain. My main research interests focus on how phosphorylation of CTD is regulated and how this phosphorylation affects the outcome of transcription, and in turn, how these processes are involved in important biological phenomena such as cancer and neurogenesis. Ultimately, we aim to exploit the results from this research in the design of small molecule effectors that can intervene in the CTD processes and thereby function as regulators of gene expression.

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the university
The University of Texas at Austin (www.utexas.edu) is a state-supported institution, and the flagship school of the University of Texas System. The University was founded in 1883 with 221 students and 8 faculty members, and has since grown into a major research university with over 49,000 combined graduate and undergraduate students, and over 2,700 faculty members. The Biochemistry, Cell and Molecular Biology and Microbiology programs are centered in the College of Natural Sciences, The College of Pharmacy and the Cockrell School of Engineering. The Colleges have 9 departments, including the life sciences as well as Chemistry, Physics, Mathematics, Astronomy and Computer Science. We have close associations with the Dell Pediatric Research Institute, the NeuroTexas Institute and in 2016 the Dell Medical School will open at the University of Texas at Austin, significantly expanding biomedical research on campus. The University of Texas at Austin works to make the world a better place by leveraging its research and knowledge to address the needs of the state, the nation and the world. This list of some of our recent rankings and kudos highlights the universitys depth of

resources, talent and technology. The university ranked 12th in Newsweek magazines 2010 list of the 25 Most Desirable Large Schools. The ranking takes into account openness and diversity, as well as distinction in research. The University of Texas at Austins Blanton Museum of Art is the the largest university art museum in the country and the third largest art museum in Texas. In a recent report on the innovativeness of universities worldwideconducted by the Research Center for Innovation and Development of Zhejiang University in Hangzhou, ChinaThe University of Texas at Austin ranked No. 4 among 200 institutions around the world. The Times of London, in its Nov. 5, 2004, edition, rated The University of Texas at Austin seventh in the world in the amount of cited research by faculty members. The University of Texas System ranks No. 1 for biotechnology patents among 424 universities in the world, according the Milken Institute and its September 2006 report on universities biotechnology research and commercialization. We are very excited about UTs shared commitment to offer leading-edge childrens healthcare, research and education right here in Austin, Susan Dell, co-founder and chairman of the Michael & Susan Dell Foundation said in announcing grants of $50 million to establish three new worldclass facilities at UT Austin. These new facilities are a perfect complement to other investments weve made in childrens health...This is a great opportunity to take advantage of UT Austins historical excellence in Life Sciences research and, in turn, make a practical difference in the lives of children. (The University of
Texas System News

Discoveries made at UT Austin help stimulate our economy. Companies such as (Molecular Imprints, LabNow, Entercel and Proactive Technologies) commercialize the discoveries made on campus or when they are licensed to companies. Most of these discoveries come about as a result of the massive amount of research grants to UT Austin. The large research enterprise on the Forty Acres has pulled in nearly $400 million in research grants. The Neal
Spelce Austin Newsletter

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mission
The mission of The University of Texas at Austin is to achieve excellence in the interrelated areas of undergraduate education, graduate education, research and public service. The university provides superior and comprehensive educational opportunities at the baccalaureate through doctoral and special professional educational levels. The university contributes to the advancement of society through research, creative activity, scholarly inquiry and the development of new knowledge. The university preserves and promotes the arts, benefits the states economy, serves the citizens through public programs and provides other public service.

core values
Learning - A caring community, all of us students, helping one another grow. Discovery - Expanding knowledge and human understanding. Freedom - To seek the truth and express it. Leadership - The will to excel with integrity and the spirit that nothing is impossible. Individual Opportunity - Many options, diverse people and ideas; one university. Responsibility - To serve as a catalyst for positive change in Texas and beyond.

Each member of the University is expected to uphold these values through integrity, honesty, trust, fairness, and respect toward peers and community.

core purpose
To transform lives for the benefit of society. What starts here changes the world.

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austin
Austin is a difficult place to categorize, at once the least Texan and the most Texan of cities. With a burgeoning high-tech industry, a university population of close to 50,000, the endless carnival of Texas statehouse politics and a music and restaurant scene that would be envied by a city twice its size, Austin is a mecca for writers, scholars, Hollywood stars and others where the great myths of Texas seem to find their most eloquent voice. New York Times, January 10, 1999 Austin is nicknamed the Live Music Capital of the World, and with more than 125 music venues, Austin offers a complete range of musical styles from rhythm and blues to hard rock, country to Tejano. When you visit Austin, or if you decide to live here, youll have no shortage of interesting and satisfying places to eat. Austins restaurants are a feast for the mind and the palate. Austin has many high-end, destination restaurants, but it also has many highquality, unique, and inexpensive restaurants where the locals eat, drink, and socialize every day (all day). Its a town built for living in, and the affordable, excellent restaurants show it. Just so you know youre in Texas, Austin has a large number of places serving Texas Barbeque and Tex-Mex; many of them are venerable, famous, and exceptionally good eating. Wikitravel (2011)

#1 Best Cities for the Next Decade Forbes (2010) #1 Best Local Music Scene Budget Travel (2010) #1 Americas Coolest City Forbes (2005) #1 Best City for Hispanics Popular Hispanics (2011) #1 US City with the Most Vital Economy Moodys
Economy (2007)

American Capital of Culture American Capital of Culture

(2004)

Best Little City in America National Geographic Society

(2006)

#2 One of the Coolest Cities in America NBC (2003) #2 Best People in Americas Favorite Cities Travel &
Leisure (2004)

#2 Best Big City to Live Money Magazine (2006) #2 Best Places to Live Mens Journal (2006) #2 Top 10 Green Cities Green Guide (2007) #3 Best City to Move To RelocateAmerica.com (2010) #3 Best City for Singles Yahoo Travel (2011) #3 Most Dog-Friendly City DogFriendly.com (2010) #4 Best Loved Cities Travel & Leisure (2003) #4 Best City for Women Ladies Home Journal (2002) #5 Smart Places to Live Kiplinger.com (2006) #5 Most Educated City in the U.S. US Census Bureau #5 Safest Big City Morgan Quitnos 12th Annual Safest City
Awards 2006

We enjoy 300 annual days of sunshine, 220 city parks, 27 golf courses, 9 wilderness areas, 150-mile long chain of lakes, 16,682 acres of greenbelt for recreation, 30 miles of urban hike-and-bike trails along Town Lake and Barton Springs, 125 live music venues with 1200 musical acts annually, and some really great sports. We are home to professional symphony, ballet, and opera companies, more than 35 art galleries and museums. Austin is the top location for moviemaking in Texas, and home to several famous directors. The South by Southwest music, film and interactive festival, brings 200,000 industry professionals and fans to Austin each year. The Austin City Limits Music Festival which attracts more than 75,000 people each year Festival of the Year Pollstar (2006)

#5 Cleanliness Americas Favorite Cities Travel &

Leisure (2004)

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