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Interdisciplinary Biomedical Research Program (IBRP)

 
   
 

Carl Anderson, Ph.D.
Senior Scientist and Chair, Biology Department, Brookhaven National Laboratory.
Funding through the National Cancer Institute, U.S. Army, and the Department of Energy.


Figure 1. p53 ChIP-GST method for analyzing p53 binding sites in human genomes. The human genome is a complex architecture of proteins and DNA that together specify and regulate the expression of the information necessary to specify life. Nornal human cells have ~88,500 predicted p53 binding sites but only ~1000 – 10,000 p53 molecules. To experimentally determine the actual sites with which p53 interacts under any give experimental or physiological condition we have developed a new technique, ChIP-GST (Chromatin Immunoprecipitation – Genome Signature Tags, that should be capable of identifying and quanfying all of the sites in a genome with which a sequence-specific binding protein, such as p53, actually interacts.

The p53 tumor suppressor is a tetrameric transcription factor that regulates the expression of approximately 1,500 genes that control cell fate in response to stress. Using a new method developed at BNL, Chromatin Immuno-Precipitation Genome Signature Tags (ChIP-GST), the whole human genome will be analyzed to determine the sites with which p53 interacts in normal cultured human cells and after genotoxic stress. This analysis represents the first whole genome analysis for functional interaction sites of any human sequence-specific binding protein and will give, for the first time, a nearly complete set of all sites in the human genome with which p53 binds.

A student with strong computational and/or mathematical background would represent a welcome addition to this research program and would participate in the development of algorithms to identify and classify the subset of genomic sites with which p53 interacts as a function of the type of stress, growth state, and cell type.

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