TCF4 Simulation Video

MD Simulation of TCF4 bound to CREB-binding protein video

by Ryan Godwin, Ph.D. student, Department of Physics, Wake Forest University

Sam Cho, Ph.D, Assistant Professor, WFU

Class name: PHY 320/620: Physics of Biological Macromolecules, Fall Semester 2012

View video here:

TCF4 and CREB-binding Protein MD Simulation from Sam Cho on Vimeo.

Final Project: MD Simulation of TCF4 bound to CREB-binding protein 

Project description: Our class performed molecular dynamics (MD) simulations of TCF4 bound to CREB-binding protein on Wake Forest University’s DEAC Supercomputing facilities. Molecular dynamics simulations are like a computational microscope that describes the physical movements of atoms and molecules over a period of time. The forces between each of the atoms and molecules at a given time determine where they will move next by numerically solving Newton’s equations of motion, over and over again until the simulation ends. The result is a series of “snapshots” that can be stitched together into a “movie” like the one seen above.

In previous years, we chose some obscure biomolecular system to perform our simulations. This year, to give the students a more meaningful experience, they performed simulations of TCF4 bound to CREB-binding protein, whose structure was recently solved using a technique called nuclear magnetic resonance by an international team consisting from Queen’s University (Kingston, ON), University of Toronto (Toronto, ON), and Centre National de la Recherche Scientifique (Grenoble, France). This was an ideal biological system to study because it was just the right size for the students to perform scientifically meaningful simulations in a short period of time.

On the last day of class, Theresa and Paúl Pauca shared their story of their son Victor so that the students can know that their simulations had a biological relevance.  This talk was designed to encourage socially relevant learning and disability awareness at the University level.

Student comments about the class:
“I especially enjoyed seeing how our project was useful to good people.”
“I enjoyed the simulations and applying what we learned in the semester to understand the real-world applications of the theory.”

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Grant Recipients, Spring 2013

David Sweatt, PhD 

Evelyn F. McKnight Chair, Dept of Neurobiology; Director, McKnight Brain Institute; University of Alabama at Birmingham

The identification of the dysfunctional TCF4 transcription factor gene as the genetic basis of Pitt-Hopkins Syndrome is a critical step forward in beginning to understand the diagnosis, etiology and molecular biology of PTHS. This project encompasses a set of studies to investigate the cognitive dysfunction associated with PTHS, focusing on mechanistic studies to understand the role of the TCF4 transcription factor in central nervous system function. For this project we are using genetically engineered mice in which the TCF4 gene has been manipulated in order to mimic human PTHS. This particular project is focused on investigating whether there is aberrant regulation of epigenetic molecular mechanisms, and altered transcriptional regulation of genes and small non-coding gene products in the PTHS model mice. For these studies we are particularly interested in learning and memory function as it relates to these molecular biological mechanisms in the CNS. Toward that end we are using next-generation high-throughput DNA sequencing methodologies coupled with epigenomics and bio-informatics approaches.

Stephen J. Haggarty, PhD

Associate Professor of Neurology | Harvard Medical School and Massachusetts General Hospital

The additional funds will be used to further support a post-doctoral research scientist in the Haggarty laboratory who is developing assays with human patient specific, stem-cell derived neuronal to measure TCF4 expression at the mRNA and protein level. Additionally, methods for mapping TCF4 target genes using state-of-the-art techniques for chromatin immunoprecipitation coupled with high-throughput DNA sequencing (ChIP-seq) are being piloted. These studies are anticipated to provide important new insight into how the loss of TCF4 function may lead to changes in pathways important for neuroplasticity.

 

 

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Verbal Victor App

 

To honor Hispanic Heritage Month, NBC Latino is honoring and featuring 20 Hispanic-Americans pioneering change in the country and in the community.

PAUL PAUCA dreams up app to communicate with disabled son

by Sandra Marquez Stathis
5:00 am on 09/18/2012 

Pauca-Innovator

The diagnosis came when little Victor was just 2 1/2 years-old. The North Carolina boy was afflicted with a rare developmental and cognitive condition that causes delays in speech and motor skills called Pitt Hopkins Syndrome, of which there are approximate 180 cases worldwide. Mom and dad, who had noticed something was wrong at one year just as Victor was only starting to sit up, were heartbroken.

“It shattered our world,” remembers Paul Pauca, Victor’s father, a Peruvian-born software engineering professor at Wake Forest University in Winston-Salem. “It got dark and very, very negative.” But his wife, Theresa, a special education teacher, helped Pauca see things more clearly, telling him he had the option of “becoming bitter or better” and that waiting for him on the other side was his baby boy.

It was a message Paul took to heart—and directly into his classroom at the university, where he enlisted his students to help build an iPhone app for kids like Victor, whose condition also caused a delay in his speech. Pauca understood the need: previous devices for children with communication challenges were expensive—ranging in price from $300 to upwards of $8,000—and impersonal.

So his team developed the Verbal Victor app, which now sells for $6.99 in Apple’s iTunes store, and allows the child to hear familiar voices talking to him. The app shows pictures in the form of buttons on mobile devices. When a child touches the picture of, say, a swing, a recorded voice, usually that of their parent or a sibling, says a word or a sentence such as: “I want to play.”
“One of the features I really love is that parents can customize it with their own voices so it doesn’t have a generic, robotic voice,” says Pauca. The recordings can also be made in any language, says Pauca, “which means I can also talk to Victor in Spanish.”

In the four years since Victor’s diagnosis, and since the app first hit the market, Pauca’s life has been completely transformed. On a new professional course as an international advocate for Pitt Hopkins, he is now also a developer of mobile apps for children and adults with disabilities. “Victor brought meaning and purpose to my work,” Pauca says. “My wife and I have started a foundation. And my daughters are becoming leaders in disabilities and trying to change the world in their own way.” In fact, philanthropy runs in Pauca’s family. His father is a retired mechanical engineer who has created 14 libraries for indigenous communities in Peru, and his mother is a social worker.
Victor, who finally learned to walk at age two, now spends his afternoons riding his tricycle and playing on his backyard swing set. ”He’s an extremely curious little guy,” says Pauca. “He’s very lively and social. And he loves having books read to him.”
Meanwhile, the communication tool his Dad named after him has helped prepare Victor to engage with the world around him. “He’s now pointing at himself and then pointing at what he wants,” says Pauca. “Verbal Victor has taught him that if you touch this button, something you want is going to happen. It motivates him to try and go to the next level, to try and say it or to click.”

http://nbclatino.com/2012/09/18/innovator-paul-pauca-creates-communication-app-to-help-his-son/#.UFiV23MvsGc.twitter

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