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.
Jin Kim Montclare, associate professor of chemical and molecular engineering at NYU-Poly, and Yingkai Zhang, associate professor of chemistry at NYU, have teamed to study the functioning of one of the key proteins in human DNA, called histone. 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, of 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.
The National Institutes of Health grant will provide $1.2 million over four years.
The Polytechnic Institute of New York University (formerly the Brooklyn Polytechnic Institute and the Polytechnic University, now widely known as NYU-Poly) is an affiliated institute of New York University, soon to be its School of Engineering. NYU-Poly, founded in 1854, is the nation's second-oldest private engineering school. It is presently a comprehensive school of education and research in engineering and applied sciences, rooted in a 159-year tradition of invention, innovation and entrepreneurship. It remains on the cutting edge of technology, innovatively extending the benefits of science, engineering, management and liberal studies to critical real-world opportunities and challenges, especially those linked to urban systems, health and wellness, and the global information economy. In addition to its programs on the main campus in New York City at MetroTech Center in downtown Brooklyn, it offers programs around the globe remotely through NYUe-Poly. NYU-Poly is closely connected to engineering in NYU Abu Dhabi and NYU Shanghai and to the NYU Center for Urban Science and Progress (CUSP) also at MetroTech, while operating two incubators in downtown Manhattan and Brooklyn. For more information, visit http://www.poly.edu.
Founded in 1831, NYU is one of the world's foremost research universities and is a member of the selective Association of American Universities. NYU has degree-granting university campuses in New York, Abu Dhabi, and Shanghai; has eleven other global academic sites, including London, Paris, Florence, Tel Aviv, Buenos Aires, and Accra; and sends more students to study abroad than any other U.S. college or university. Through its numerous schools and colleges, NYU conducts research and provides education in the arts and sciences, law, medicine, business, dentistry, education, nursing, the cinematic and performing arts, music and studio arts, public administration, social work, and continuing and professional studies, among other areas.