Our genomes encode the blueprint for life. Buried in the genome are both the building blocks ("genes") and instructions on when and where each gene is to be used. There is now strong evidence that changing when and where genes are used is both a major component of evolution, and also can be a major contributor to disease risk.
The Duke/Princeton Genomics of Gene Regulation project will seek to reveal new insights into how genes are regulated by focusing on a single and well-controlled system, the glucocorticoid response. The glucocorticoid response has dual roles in the human body, controlling both metabolism and the immune system. It is one of the reasons you get hungry at the same time every day, and also the way your body prioritizes certain functions over others in times of extreme stress. For example, glucocorticoids act to reduce inflammation if you are being chased by a tiger. This makes sense, as you don't want sore knees to be the reason the tiger was able to catch and eat you. It is this anti-inflammatory activity of glucocorticoids (think: cortisone cream, prednisone) that also makes them among the most widely used drugs today.
The major goal of this project is to figure out all of the part of the genome that determine how genes are used in response to glucocorticoids; and then to figure out how all of those pieces talk to each other. In the end, we will use this information to see if we can change the way cells respond to these drugs. In other words, can we make a modified glucocorticoid response that is better at reducing inflammation, but doesn't impact metabolism quite so much?
This project is one of five projects funded simultaneously by the National Human Genome Research Institute (NHGRI) with the common goal of learning how genes are turned on and off. You can read all about these projects at the official NHGRI press release. We are extremely excited to be starting in on this project, and look for our data hitting the public repositories in the coming months!
This project leverages synergy between investigators at Duke (Reddy, Crawford, Gersbach, and Hartemink) and Princeton (Engelhardt). The investigative team is highly multidisciplinary, spanning several schools and departments within Duke, and synergy between the investigators will allow for close connections between generating data, building and refining network models, and ultimately reprogramming the glucocorticoid response.