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.
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.
Decoding and reprogramming the corticosteroid transcriptional regulatory network
As part of the Genomics and Gene Regulation project funded by NIH, this research project, led by the Reddy lab, explores the human body's response to chronic stress. Although it is already known that the body releases cortisol when stressed, this project explores the complete mechanism of how cortisol impacts the function of various cell types and tissues. As a drug, cortisol is a potent anti-inflammatory molecule. However, it also has many metabolic side effects, including the increased risk of diabetes. Tim Reddy, Alex Hartemink, Greg Crawford and Charlie Gersbach are collaborating on this study by using a variety of high-throughput assays and integrative analyses to comprehensively characterize how cortisol impacts the body and explore ways to separate out the negative side effects of this very powerful drug.