GCB encompasses a group of researchers who thrive in a highly collaborative and multidisciplinary environment. Our faculty members come together to answer questions that would not be possible within a single discipline.
Duke Center for Combinatorial Gene Regulation: A Center of Excellence in Genomic Science
Five of the seven PIs on this interdisciplinary research team are members of GCB: Tim Reddy, Andrew Allen, Greg Crawford, Charlie Gersbach and Greg Wray. They, along with PIs Warren Kibbe, professor of biostatistics and bioinformatics, and Vandana Shashi, professor of pediatrics, are working to fundamenally transform the understanding of combinatorial regulatory mechanisms in the human genome. Their goal is to make combinatorial studies of the function of regulatory elements and noncoding variants routine. The culmination of this project will be the first systematic and comprehensive framework for determining the effects of combinations of regulatory elements on gene expression and downstream phenotypes. That outcome will transform human disease studies by newly prioritizing thousands of genes for targeted study and drug design. This project will also be a major step towards predicting the pathogenicity of noncoding variants that have not been observed, which is key for whole genome sequencing studies of both rate and common disease. This is the first NIH Center of Excellence in Genome Science grant Duke has received.
It takes a village: Gene Regulation in Cooperative Societies
As part of a Human Frontiers Science Grant, Jenny Tung and Sayan Mukherjee are collaborating with Luis Barreiro at the University of Montreal and Tim Clutton-Brock at the University of Cambridge to study a natural population of meerkats in the Kalahari Desert in South Africa. They are investigating the nature of tradeoffs between investment in reproductive effort and growth versus somatic maintenance. Meerkats live together in big clans, but only one female and a couple of males are breeders. The rest of the clan serve as helpers and aid in raising the pups. The group has a cell culture lab in the Kalahari Desert where they can quickly collect samples from both breeding and nonbreeding meerkats and conduct basic cell culture experiments to see whether cells from breeding individuals respond differently to pathogen threats from non-breeders.
Deciphering repeat sequences on transcriptional regulation of disease genes
Funded through the Holland Trice Scholars Award for high risk/high impact discovery in research in basic brain science and diseases, Raluca Gordân and Ornit Chiba-Falek collaborated on a project to investigate the effect of polymorphic repeat sequences on transcriptional regulation in the human brain in relation to neurodegenerative diseases. They showed that repetitive sequences can directly influence transcription factor binding to their proximate recognition sites, a mechanism they termed non-consensus binding. The team focused on a simple sequence repeat (SSR) Rep1, which is associated with Parkinson’s disease and has been implicated in the cis-regulation of the Parkinson’s disease SNCA gene. They investigated the effect of the Rep1 polymorphism on the binding of transcription factors from the GATA and ELK families and discovered that Rep1 modulates the affinities of the binding. Their findings suggest that Rep1 functions via the non-consensus binding mechanism to regulate the SNCNA in human brain tissue.