Mark Eliot Dumont, Ph.D.

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G protein signaling: G protein coupled receptors mediate cellular responses to a variety of sensory stimuli, hormones, growth factors, and neurotransmitters and are targets of a number of widely prescribed drugs. Signal transduction by G protein coupled receptors occurs when an activated receptor interacts with a trimeric G protein in the cytoplasm, causing the G protein to release a bound molecule of GDP and to replace it with a molecule of GTP. The mechanisms by which ligand binding leads to activation of the intracellular G protein remain poorly understood. We are using a combination of genetic and biochemical methods to study the yeast ?-factor receptor that prepares yeast cells for mating in response to binding of the mating pheromone, ?-factor. Components of this yeast signal transduction pathway are homologous to, and in some cases functionally interchangeable with, corresponding components of mammalian signaling systems. However, the ability to easily select or screen for functional and non-functional receptors in yeast allows rapid identification of receptors with interesting mutations from among a randomly mutagenized population in a way that is not possible in mammalian systems. We are currently analyzing classes of mutations that can provide information on the structure of the ?-factor receptor, on interactions between receptors, and on the mechanism of activation of G proteins by receptors.

Genomic approaches to membrane protein structure and function: Although membrane proteins constitute 20-30% of the coding potential of genomes, methods for analyzing their structures and functions are still primitive compared to the approaches available for studies of soluble proteins. We are pursuing two projects that involve expression of membrane proteins on a genomic scale. One of these is the large scale expression and purification of membrane proteins encoded in the genomes of pathogenic protozoans for use in x-ray crystallography. The other, conducted in collaboration with the laboratories of Eric Phizicky and Elizabeth Grayhack, is the expression and purification of a complete set predicted reading frames from genome of bakers' yeast Saccharomyces cerevisiae for use in identifying genes encoding membrane-related enzyme activities.

Current Appointments

• Professor - Department of Biochemistry and Biophysics (SMD)
• Professor - Department of Pediatrics (SMD)