Medical Research

University of Virginia

Eyleen O'Rourke, Nathan Lewis, George Church
Charlottesville, VA
$1,200,000
June 2016

Multicellular organisms are ultimately complex genetic networks integrated in ascending levels of complexity (cells, tissues, organs).  Human diseases are network diseases.  Even family members exposed to the same agent or carrying the same mutation can develop mild to severe symptoms because the response of their individual gene networks is different, and those differences determine the severity of the disease.  Thus, multilevel functional gene network reconstruction and modeling could transform our understanding of biology and our ability to discover disease mechanisms and rationalize the design and testing of new treatments.  However, the technologies necessary to generate multilevel animal models have not yet been developed.  Using the nematode C. elegans as their model system, a team of investigators from the University of Virginia, the University of California San Diego, and the Wyss Institute plans to develop the technologies to measure gene expression and fat metabolism that will make possible the first single-cell resolution metabolic model for an entire living animal.  The tools and computational frameworks to be established will enable modeling of vertebrate animals, human tissues and organs, the microbiome, or any other complex communities of cells with critical multicellular structure.  The detailed landscape of gene expression and function across a complex multicellular organism that will emerge from this work has never been accomplished before, and it is expected to open new doors in biology and biomedicine.

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