Michael R. Koelle, Ph.D.

Research

Neurotransmission through G protein coupled receptors modulates the activities of neurons and may underlie some forms of memory in higher organisms. We identify and study behavioral mutants of the nematode C. elegans in which this form of neurotransmitter signaling is defective. By cloning the genes defined by these mutations we can identify the molecules responsible for signaling. The lab has also expressed and purified recombinant forms of the signaling proteins we identified genetically and we are using these proteins to investigate the biochemical mechanisms underlying neural signaling. Using these approaches, we discovered a large family of Regulators of G Protein Signaling (RGS proteins) that directly inactivate G proteins. We are carrying out both biochemical and genetic studies of RGS proteins to find out how and why cells use these regulators. Our genetic experiments also identified a protein that may be the direct target activated by the major neural G protein. We are currently analyzing the interactions of the purified G protein with this purified target protein. We plan to clone and analyze the many other signaling genes we have identified genetically that mediate neurotransmission.