Leland H. Hartwell
Arizona State University
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Primary Section: 22, Cellular and Developmental Biology Membership Type:
Member
(elected 1987)
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Research Interests
My laboratory is beginning a new research program aimed at understanding the relationship between phenotype and genotype with emphasis on the genetic variation that accumulates in outbred populations. A variety of biochemical mechanisms (including gene redundancy, co-assembly of proteins into macromolecular complexes, negative feedback, robust circuit design, repair processes) minimize the phenotypic consequences of genetic variation and thereby allow cells and organisms to tolerate it. These relationships can be revealed by synthetic-phenotypes. That is, if one gene plays a role that buffers the phenotypic expression of variation in another, then loss of the first reveals the phenotypic consequences of variation in the second. Synthetic-lethal relationships have been widely studied in yeast although rarely systematically or comprehensively. Anecdotal results strongly suggest that buffering mechanisms are modular. That is, the cellular circuitry is organized into modules that buffer the expression within their module but may not affect other modules. We are developing methods to be both systematic and comprehensive in the investigation of synthetic phenotypes and are focusing on tolerance of genetic variation in the DNA synthetic apparatus, the galactose metabolic pathway and the permeases that transport arginine and lysine into the cell.
