A Chemical Biology Approach to Epigenetics

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A Chemical Biology Approach to Epigenetics

Monday, January 25, 2010

The New York Academy of Sciences

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The Chemical Biology Discussion Group brings together chemists and biologists interested in learning about the latest ideas in this rapidly growing field. It provides a forum for lively discussion and for establishing collaborations between chemists armed with novel technologies and biologists receptive to using these approaches to solve their chosen biological problems. Post-docs from the chemical biology community in the New York area have organized this special meeting.

Agenda

The Enzymatic Activity of Sirtuins: Beyond NAD-Dependent Deacetylation
Hening Lin, Cornell University

Sirtuins, NAD and Dietary Restriction Combine to Modulate Epigenetic States, Gene Expression and Protein Activity
Anthony Sauve, Weill Cornell Medical College

Molecular Recognition of the Nucleosome
Song Tan, Penn State

Networking Reception to Follow

Organizers

Yana Cen

Weill Cornell Medical College

Danielle Guarracino

New York University

Carl Machutta

GlaxoSmithKline

Sofia B. Rodriguez

Albert Einstein College of Medicine

Zhongping Tan

Memorial Sloan-Kettering Cancer Center

Speakers

Hening Lin

Cornell University

Hening Lin is currently Assistant Professor in the Department of Chemistry and Chemical Biology at Cornell University. He was a postdoctoral fellow in the Christopher Walsh lab at Harvard Medical School. He received his BS in Chemistry from Tsinghua University, Beijing, China and his PhD in Bioorganic Chemistry from Columbia University.

Anthony Sauve

Weill Cornell Medical College

Anthony A Sauve was born in Los Angeles. He attended UC Berkeley and received a BA in Biochemistry. He received his PhD in Chemistry from Princeton University. He was an NIH post-doctoral fellow in the laboratory of Professor Vern L Schramm at Albert Einstein College of Medicine in the Bronx. He is currently an Associate Professor of Pharmacology at Weill Medical College of Cornell University. Dr Sauve has been an influential contributer to understanding the enzymology of ADP-ribosylating enzymes and has published numerous papers in the sirtuin and NAD field. He has been a member of the Scientfic Advisory Board of Sirtris Pharmaceuticals since 2005.

Song Tan

Penn State University

Song Tan is Associate Professor of Biochemistry and Molecular Biology at Penn State University. He received his BS in Physics from Cornell University, and his PhD in Molecular Biology from the University of Cambridge. As a postdoc and a project leader in Tim Richmond's laboratory at the ETH-Zurich in Switzerland, he determined crystal structures of multicomponent protein-DNA complexes. The Tan laboratory uses biochemical and structural methods, including X-ray crystallography, to understand how chromatin factors and enzymes recognize their nucleosome substrate.


Abstracts

The Enzymatic Activity of Sirtuins: Beyond NAD-Dependent Deacetylation

Hening Lin, Cornell University

Sirtuins have been recognized as NAD-dependent deacetylases that regulate important biological processes, including life span, transcription, cell survival, and metabolism. Mammals have 7 sirtuins, SIRT1-7. Of the seven human sirtuins, only three of them, SIRT1, SIRT2, and SIRT3, have robust deacetylation activities in vitro and in vivo. The other sirtuins either have no detectable or very weak deacetylation activity in vitro. I will present our work demonstrating that sirtuins with no or very weak deacetylation activity have other enzymatic activities that may regulate transcription and other biological processes.

Sirtuins, NAD and Dietary Restriction Combine to Modulate Epigenetic States, Gene Expression and Protein Activity

Anthony Sauve, Weill Cornell Medical College

Sirtuins are biologically conserved protein deacetylases that react NAD with histones and other proteins, such as transcription factors and enzymes, thus regulating diverse biological processes. Sirtuin enzymes are highly responsive to changes induced by dietary restriction and appear to mediate a number of potent biological effects attributed to reduced calorie intake, such as increased lifespan. This seminar will explore how nature uses the highly conserved catalytic site of sirtuins to accomplish lysine deacetylation. In addition, studies to determine how sirtuin activities are linked to dietary restriction will be examined.

Molecular Recognition of the Nucleosome

Song Tan, Penn State University

Although we have a reasonable understanding of how proteins bind to DNA, we lack an equivalent understanding of how chromatin enzymes and factors interact with chromatin. My laboratory is investigating how the chromatin factor RCC1 (regulator of chromosomal condensation) interacts with the nucleosome to regulate mitosis, nucleocytoplasmic transport and nuclear envelope dynamics. Our biochemical studies and our crystal structure of the 300 kD RCC1/nucleosome core particle complex show us for the first time the molecular details of how a chromatin factor recognizes the nucleosome.

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