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Transcript
SMART Teams 2015-2016
Research and Design Phase
Westosha Central High School SMART Team
John Dietz, Jared Holloway, Trevor Millhouse, Connor Muff, Victoria Salerno,
Zach Wermeling, Lucas Wysiatko
Advisor: Jonathan Kao
Mentor: SuJean Choi, Ph.D.
Marquette University, Department of Biomedical Science
Regulating Jeans with Genes – A Protein Driven Pathway to Appetite Suppression
PDB: 1BND
Primary Citation: Rios, M. (2013). BDNF and the central control of feeding: Accidental bystander or
essential player? Trends Neurosci, (2), 83-90.
Format: Alpha carbon backbone
RP: Zcorp with plaster
Description:
According to the World Health
Organization, over 1.9 billion people in the
world are overweight. Many of these
people are overweight as a direct result of
overeating. Obesity could potentially be
treated by inducing an anorexigenic
response, or loss of appetite. Several
neurotransmitters are involved in signaling
for appetite suppressing or stimulating
responses. BDNF, the brain-derived neurotrophin factor, works as one of many appetite regulators in
the ventromedial nucleus (VMN) in the hypothalamus. Injection of BDNF into rat VMN has been shown
to drastically reduce appetite, increase metabolism, and ultimately lead to weight loss. Conversely,
knockout of BDNF has been shown to lead to overeating and obesity. BDNF has a high affinity for the
receptor Trk-B due to neurotrophins having variable binding domains. The Westosha Central SMART
(Students Modeling A Research Topic) Team modeled BDNF as it binds to Trk-B. Once bound,
transduction sends a cascading signal that can stop feeding behavior. Various signals have been shown
to affect BDNF concentration leading to anorexigenic and orexigenic responses. BDNF concentration
correlates with increased leptin, a hormone made by adipose tissue, physical activity, and
glutamate. Concentrations of BDNF decrease as the neurotransmitter GABA increases. Understanding
BDNF production and signaling provides researchers with a better opportunity to control expression and
elicit a specific response in an attempt to treat obesity or eating disorders.
Specific Model Information:
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The backbone of the model is colored lightskyblue
The alpha helices are colored seagreen
The beta sheets are colored dodgerblue
Six cysteine sidechains are highlighted in gold. These six cysteines form a “cysteine knot” that
holds the protein chain together.
Amino Acids 41-50 are defined as “Loop 2” and bind with the TrkB receptor. These amino acids are
highlighted in firebrick.
Hbonds are colored in lemonchiffon
Struts are colored in burlywood
http://cbm.msoe.edu/smartTeams/index.php
The SMART Team Program is supported by the National Center for Advancing Translational Sciences,
National Institutes of Health, through Grant Number 8UL1TR000055. Its contents are solely the
responsibility of the authors and do not necessarily represent the official views of the NIH.