Dr. Phanstiel, a UNC Assistant Professor of Cell Biology & Physiology, and faculty member in the UNC Thurston Arthritis Research Center, has been awarded a 5-Year, $1.25 million grant for his research into how human cells regulate gene transcription during development. His research is focused on better understanding how DNA folds within the cell nucleus, specifically which proteins are involved in governing that folding, and how the resulting three-dimensional structure of chromatin regulates gene transcription. This research addresses fundamental questions regarding how our cells work and how each person’s unique DNA sequence contributes to their development and susceptibility to disease. The results will aid our understanding of a variety of human diseases ranging from arthritis to cancer.
The goal of the “MIRA” grants is to increase the efficiency of NIGMS funding by providing investigators with greater stability and flexibility, thereby enhancing scientific productivity and the chances for important breakthroughs.
More detailed information regarding Dr. Phanstiel’s Research:
Chromatin loops spanning tens to hundreds of kilobases link promoter-distal regulatory elements such as enhancers to the promoters of their target genes. Many of these loops are cell-type specific and are thought to play a critical role in transcriptional control during cellular differentiation and human development. Recent progress in our ability to detect these loops has significantly advanced our knowledge regarding the molecular components of DNA loops; however, the mechanisms and functions of changes in DNA looping during cellular differentiation remain poorly understood.
The goals of Dr. Phanstiel’s research are to identify the mechanisms through which cells establish new loops during cellular differentiation and to determine how the resulting structures contribute to altered transcriptional output. We will accomplish these goals by: (1) mapping loops, regulatory events, and gene transcription with temporal resolution during cellular differentiation, (2) developing and applying new software to identify and visualize dynamic looping events, and (3) performing targeted mechanistic investigations of loops formed during differentiation. The results of this research will determine both the scope and general principles of DNA loop formation during differentiation, provide new tools for the gene regulation community, and illuminate the functions of the non-coding human genome.