$9 million award will enable discovery of the DNA sequences that regulate genes

Functional factors from fruit flies first step toward human effort

May 14, 2007

The National Human Genome Research Institute, part of the National Institutes of Health, has awarded $9.1 million over four years to a research team led by the University of Chicago to identify all regulatory elements, the DNA sequences that control when and where specific genes get turned on or off, in the fruit fly genome.

The award is part of a $57-million scientific mission--the ENCyclopedia Of DNA Elements (ENCODE)--to understand every part of the genome needed for organisms to develop and survive. ENCODE was created to assemble a comprehensive catalog, or "parts list," of all functional elements in the human genome.

Early genome studies focused on the genes that code for proteins. This project takes the next step, shifting the focus to the regulatory elements that control gene transcription.

Dubbed model-organism ENCODE (modENCODE), this new focus will apply innovative methods and technologies for the study of gene regulation to the smaller, and therefore more manageable, genomes of the fruit fly (Drosophila melanogaster) and the round worm (Caenorhabditis elegans).

"Our project will serve as a pilot for the full-scale mapping of functional regulatory elements in the human genome," said program director Kevin White, PhD, the James and Karen Frank Family Professor in the departments of Human Genetics and Ecology & Evolution, and Director of the Institute for Genomics & Systems Biology at the University of Chicago and Argonne National Laboratory.

"The fruit fly genome is the ideal model for the study of regulatory elements," White said. "It shares the structure and many features of the human genome; many human proteins function just as well in fruit flies. Yet it is small enough for high-resolution genome-wide analysis."

"Beginning with Drosophila allows us to test our predictions in live animals, the only way to experimentally validate our computational methods," he added. And "there are now 12 fully sequenced fruit fly species, a rich database for comparative genomics."

Scientists rely heavily on such model organisms to identify common genes, proteins and processes that underlie human medical conditions. "The knowledge gained will help us understand many human disorders caused by malfunctions of gene regulation, a major goal of the NIH and of our new Institute for Genomics and Systems Biology in Chicago" White said.

"We are making great strides in identifying functional elements in the human genome, but we still don’t know much about their biological relevance," said NHGRI Director Francis S. Collins, MD, PhD. "This parallel effort in the fruit fly and worm genomes will provide us with information about the functional landscape of two key model organisms, which should aid our efforts to tackle such questions in humans."

The fruit fly and roundworm modENCODE projects have been designed so that similar types of elements in both organisms are being studied and catalogued in parallel. By combining and comparing data from worm, fly and human, researchers can learn far more about the functional elements than if they analyzed the genome of just one organism.

"modENCODE will enable us to confirm what we’re finding in the human genome by manipulating the fly and worm genomes in a precise and rapid way," said Elise Feingold, PhD, the NHGRI program director in charge of the ENCODE and modENCODE projects. "If a DNA sequence has been conserved throughout evolution--from worm to fly to human--it is very likely that the sequence is functionally relevant."

The modENCODE research consortium is made up of teams of experts who bring a great deal of knowledge about the biology of the fruit fly and roundworm. Due to the complexity of the data, the teams will work together to maximize the intellectual discussions and quality of data analysis. Other members of the Chicago-led team include researchers at the University of California San Diego, The Massachusetts Institute of Technology, Baylor College of Medicine and Cambridge University in England.

For more information about NHGRI’s ENCODE project, go to www.genome.gov/ENCODE.

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