Background information

Project Introduction
General information on research projects
Important recent discoveries
23 pairs of chromosome in the genome
A specific spot on the genome is called a locus
Genes create proteins in a process involving
transcription and translation
The genes code for proteins, which result in
genotypes and phenotypes
Certain gene sequences or alterations in sequence can
lead to diseases and
disorders


Some locus have a gene sequence known as repeats
Repeats are the same gene sequence repeated
Can be of varying length
Abnormal lengths can affect location of rna splicing
and gene coding
Does not follow a Mendelian pattern of inheritance
"Palindromes." Palindro
mes. N.p., n.d. Web. 03
May 2014.
<http://users.rcn.com/jki
mball.ma.ultranet/Biolo
gyPages/P/Palindrome
s.html>.
Affect around 1 in 8000
Associated with muscle weakness and wasting
Characterized by an abnormally large number of
CTG/ CUG repeats
Does not follow a Mendelian pattern of
inheritance
Myotonic Dystrophy. 2012. Photograph. By
Lubov Timchenko. Web.
DM1 is result of CUG repeats on DMPK gene
DMPK plays a role in the communication within
cells and is important for the functioning of cells
within the brain, skeletal muscles, and heart
5-37 repeats normal. 250 in DM patients

DM1 - Myotonic Dystrophy. Digital
image. Prosena. N.p., 2013. Web. 3 May 2014.
<http://www.prosensa.eu/hc-
professionals/myotonic-dystrophy>.
Expanded CUG Repeats in DM1 Result in
MBNL1 Loss-of-function and CUGBP1 Gain-of-
function. 2014. Photograph. By
Biochemsoctrans. Web.
Loss of DMPK function may lead muscle
weakness and cataracts
Accumulated repeats may be toxic to muscle
DMPK is a noncoding gene
Muscleblind-like protein 1
(MBNL1) sequestered in
the disease. They believe
that this trend affects
RNA splicing
CUG-binding protein 1
(CUGBP1) are increased
in affected tissues for
DM1 but in DM2. May be
sequestering MBNL1
levels

Expanded CUG Repeats in DM1 Result in
MBNL1 Loss-of-function and CUGBP1
Gain-of-function. 2014. Photograph. By
Biochemsoctrans. Web.
Target RNA-MNBL1 binding
Target the mutant RNA
Targeting of mismatch repair mechanisms,
methylation pathways, and developmentally-
regulated DNA replication machinery
DM1 Mice Model. Digital image. Institute Image. N.p., 2014.
Web. 3 May 2014.
<http://www.institutimagine.org/Portals/0/Imagine/Photos/Les
%20%C3%A9quipes%20de%20recherche/Genevi%C3%A8v
e%20Gourdon/GenevieG_photo1.JPG>.
Looking for therapeutic treatments towards DM1
(Myotonic Dystrophy)
DM1 results in differing levels of proteins such as
MNBL-1
Various concentration of compounds believe will
effect proteins
Testing Site
Assays
Cell Counting machine
Measures Cell Toxicity
Growing Cells

Testing Site
ROS assay (Reactive Oxygen Species)
Measures Cell Toxicity
Dichlorodihydrofluorescin diacetate (DCFH-DA) is
oxidized by ROS and a byproduct is florescence
H2O2 (hydrogen peroxide), NO (nitric oxide), O2- (oxide
anion), peroxynitrite (ONOO-), hydrochlorous acid
(HOCl), and hydroxyl radical (OH-) are examples They
play an important role in cellular signaling pathways
High levels of ROS can be very dangerous and
detrimental. However, antioxidants can change them into
harmless molecules such as water. Vitamin C and E are
antioxidants


Treatment with novel compound
Incubate and wait for cells to grow
Vacuum
Wash Buffer
Starts Reaction

Drug Treatment
Reagent
Measure
Fluorescence
Reaction Within Cell
Cell count/ grow cells
Scientific Method
Article Reading
Collaboration and building off other discoveries
or partners
Form a hypothesis based on known information
Shaker
Testing hypothesis: results should be
reproducible and multiple tests may be done
Dont always have to just test one thing
Even failures of proving hypothesis can result in
valuable articles
Formulating a Plan
Validity: How well something represents
something
Reliability: Must be reproducible
Research ethics: Foundations of scientific
research
Stem Cells
Can grow into various tissues or organs
Stem cells created naturally during the first
couple days of cell division
Studies where the stem cells have been
removed do not develop properly
Stem Cell. 2014. Photograph. By Elizabeth
Landau. Web.
One researchers recently
found that putting cells in acidic
environment leads to creation
of stem cells but people
havent been able to replicate
2013: Stem Cells used to grow
human heart tissue. precursor
heart cells called MCPs made
Using mouse scaffold, made
heart beat around 50 times a
minute


Incubator
Cancer immunotherapy:
Strengthen immune
system to fight caner.
Ipilimumab (engineered
T Cells). In melanoma
patients, 22% survived 3
years later
Sleep: Helps repair the
brain. Cerebrospinalfluid
wipes out dangerous
proteins. Twice the
speed as awake.
ALTOUNIAN. Arsenal. Digital image. Science. Sciencemag, 20
Dec. 2013. Web. 3 May 2014.
Wu, Danli, and Patricia Yotnda. "Production and Detection of Reactive Oxygen
Species (ROS) in Cancers." Journal of Visualized Experiments 57 (2011): n. pag.
Print.
Tapscott, Stephen J. "Deconstructing Myotonic Dystrophy." Biomedicine 289.5485
(2000):
1701-702. Science. Web. 5 Apr. 2014.
<http://www.sciencemag.org/content/289/5485/1701.full?sid=27b8af0b-e284-4adb-
a37c-
12a7f8396130>.
Mankodi, A. "Myotonic Dystrophy in Transgenic Mice Expressing an Expanded CUG
Repeat." Science 289.5485 (2000): 1769-772. Print.
Foff, Erin Pennock, and Mani S. Mahadevan. Therapeutics Development in Myotonic
Dystrophy Type 1. Muscle & Nerve 44.2 (2011): 160-69. Print.
U.S. National Library of Medicine. "Myotonic Dystrophy." - Genetics Home Reference.
NIH, 31 Mar. 2014. Web. 06 Apr. 2014. <http://ghr.nlm.nih.gov/condition/myotonic-
dystrophy>.
"Stem Cells Grow Beating Heart : DNews." DNews. N.p., n.d. Web. 03 May 2014.
<http://news.discovery.com/tech/biotechnology/stem-cells-grow-beating-heart-
130814.htm>.
"Cancer Immunotherapy." Cancer Immunotherapy. N.p., n.d. Web. 03 May 2014.
<http://www.sciencemag.org/content/342/6165/1432.full>.
Mrs. Click
Partha Sarkar
Parents
Yongping Liu
UTMB