NIH funds two UCSD scientists to venture deep into human genome

October 21, 2003

Two University of California, San Diego (UCSD) School of Medicine researchers will receive two of the first grants in a three-year scientific reconnaissance mission aimed at discovering all parts of the human genome that are crucial to biological function. UCSD is the only institution to receive two of the awards from the National Human Genome Research Institute (NHGRI) of the National Institutes of Health.

The new effort, funded with $36 million, is called the Encyclopedia of DNA Elements (ENCODE) project and will be carried out by an international consortium made up of 14 scientists in government, industry and academia. A consortium will be utilized due to the wide range of technologies to be tested and developed.

The UCSD recipients are:

Bing Ren, Ph.D., a member of the Ludwig Institute for Cancer Research at UCSD and a UCSD assistant professor of cellular and molecular medicine, who will receive $3.1 million for a project titled "Mapping Transcriptional Regulatory Elements in Human DNA." Working with him on the project are Christopher Glass, M.D., Ph.D., UCSD professor of cellular and molecular medicine, and Michael G. Rosenfeld, M.D., UCSD professor of medicine and a member of the Howard Hughes Medical Institute.

Xiang-Dong Fu, Ph.D., UCSD associate professor of cellular and molecular medicine, who will receive $1.4 million for "A Novel chIP-Chip Technology for ENCODE."

The grants were announced by NHGRI director Francis S. Collins, M.D., Ph.D., who led the public effort to sequence all 3 billion base pairs of human DNA. He noted that "the Human Genome Project has provided us with a wonderful foundation, but obviously having the human genomic sequence is not enough. We must keep on exploring this newfound wealth of knowledge if we are to realize the full potential of genome research to improve human health."

Ren explained that his research will test the efficiency of a genome-wide location analysis approach that he developed, to discover all on-off gene expression switches in the human genome. The analysis combines DNA microarray technologies with a biochemical purification scheme which uses specific antibodies to isolate protein-DNA complexes from living cells, to reveal the protein-DNA interactions on a genome-wide scale.

"The genome sequence is often referred to as the book of life, but mapping all the nucleotides in a genome does not immediately reveal meaning of the script," Ren said. "Learning how the human genome instructs precise expression of roughly 30,000 genes during embryo development and normal physiological processes has become the next frontier in biomedical research."

He added that his research team will devise an integrated approach combining experimental and computational methods to systemically dissect the gene expression programs encoded by the genome sequence, to understand program errors that underlie human diseases such as cancer.

Fu's research project will focus on new technologies.

"We are developing a technology that will allow identification of functional DNA elements," Fu said. "Our research will capture the DNA-protein complex formed inside cells by specific antibodies and use microarray to systematically determine the distribution of the complex in the genome. To achieve this, a robust technology is needed. Within the ENCORE project, we will further develop a new technology which we have demonstrated in a small scale in the laboratory."

He added that the new technology, called chIP-Chip, is a procedure to capture the DNA-protein complex formed inside cells, and the DNA microarray on a wafer-thin chip, which is used to identify the location and distribution of the complex in the genome.

"Our project will develop the next generation of technology for the ENCODE project," he said. "Based on our preliminary study, this technology should overcome many of the shortcoming in existing technology and allow decoding of functional DNA elements with high precision."

A major aspect of ENCODE is testing of efficient, high-throughout methods for identifying, locating and fully analyzing all of the functional elements contained in a set of DNA target regions that covers approximately 30 megabases, or about 1 percent, of the human genome. If the pilot effort proves successful, the project will be expanded to cover the entire genome.

Additional ENCODE grants are made to:

Richard Myers, Ph.D., Stanford University, Palo Alto, Calif. - "The Stanford ENCODE Project" - First year funds, $2.7 million; total funds, $8 million.

George Stamatoyannopoulos, M.D., Dr. Sci., University of Washington, Seattle - "Identification of Functional DNA Elements by HSqPCR" - First year funds, $2.3 million; total funds, $6.9 million.

Michael Snyder, Ph.D., Yale University, New Haven, Conn. - "Transcription and Regulatory Elements in ENCODE Regions" - First year funds, $1.7 million; total funds, $4.9 million.

Thomas Gingeras, Ph.D., Affymetrix, Inc., Santa Clara, Calif. - "Mapping Sites of Transcription and Regulation" - First year funds, $990,000; total funds, $2 million.

Roderic Guigo, Ph.D., Municipal Institute of Medical Research, Barcelona, Spain - "Encyclopedia of Genes and Gene Variants" - First year funds, $570,000; total funds, $1.5 million.

Anindya Dutta, Ph.D., University of Virginia, Charlottesville - "Mapping Replication Elements on Human Chromosomes" - First year funds, $380,000; total funds, $1.1 million.

Ian Dunham, Ph.D., The Wellcome Trust Sanger Institute, Hinxton, U.K. - "Detecting Human Functional Sequences with Microarrays"- First year funds, $490,000; total funds, $730,000.

Zhiping Weng, Ph.D., Boston University - "Alternative Promoter Usage in Tissue-Specific Gene Expression" - First year funds, $530,000; total funds, $1.5 million.

Robert Kingston, Ph.D., Massachusetts General Hospital, Boston - "Long-Range, High-Resolution Mapping of Chromatin" - First year funds, $430,000; total funds, $1.3 million.

Roland Green, Ph.D., Nimblegen Systems, Inc., Madison, Wisc. - "Discovery of Binding Sites for Transcription Factors" - First year funds, $400,000; total funds $1.3 million.

Mark McCormick, Ph.D., Nimblegen Systems, Inc., Madison, Wisc. - "DNA Array-based Exon Detection and Linkage Mapping" - First year funds, $400,000; total funds, $1.2 million.

Job Dekker, Ph.D., University of Massachusetts Medical School, Worcester - "Structural Annotation of the Human Genome" - First year funds, $370,000; total funds, $1.2 million.
-end-
For more information about NHGRI's ENCODE project, see www.genome.gov/ENCODE/. Additional information about NHGRI can be found at its Web site, www.genome.gov.

University of California - San Diego

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