Researchers from the Polytechnic Institute of New York University (NYU-Poly) and NYU have received a grant from the National Institutes of Health (NIH) to further a novel approach to understanding the genetic underpinnings of diseases, including cancer and diabetes.
The NIH grant will provide $1.2 million over four years.
Jin Kim Montclare, an associate professor of chemical and molecular engineering at NYU-Poly, and Yingkai Zhang, an associate professor of chemistry at NYU, have teamed to study the functioning of histone—one of the key proteins in human DNA. Histones are scaffolding proteins that organize DNA within the cell nucleus, and they are subject to modifications by enzymes that affect gene expression, both in health and disease.
Zhang and Montclare are combining their expertise in computational chemistry and protein engineering, respectively, to shed new light on one of the key enzymes that modify histones, histone acetyltransferases (HATs).
“HATs play an essential role in gene regulation, and while we know that aberrant or mutated HATs are associated with diseases like cancer and diabetes, we don’t understand their precise catalytic mechanisms,” explained Montclare. “If we can understand the processes by which these proteins can modify histones and how mutations can lead to disease, we move closer to creating targeted therapies to prevent or reverse these changes.”
The researchers’ collaborative approach is unique and has not been explored for HATs. Zhang will create a computational study of the mechanics of HATs, offering what may be the most detailed picture of their workings. This sets the stage for Montclare’s work—engineering and testing the HATs and designed variants for reactivity on histones.
“Bringing computational powers to bear on these processes will not only elucidate the underpinnings of the enzymes as they exist now, but will allow us to run simulations to test the impact of modifications and therapies to reverse the kinds of changes linked to disease,” Zhang said.