DIMACS/BIOMAPS Seminar Series on Quantitative Biology and Epidemiology.

Title: Elaborating cellular and molecular mechansims of aging in C. elegans: lessons and themes from simple old animals

Speaker: Monica Driscoll, Rutgers University

Date: Wednesday, September 24, 2003, 1:00 pm

Location: Hill Center, Room 260, Rutgers University, Busch Campus, Piscataway, NJ


Rare dominant mutations (d) in two C. elegans genes, mec-4 and deg-1, induce swelling and degeneration of different, but specific, groups of neurons in this nematode. Analysis of cloned mec-4 and deg-1 cDNAs has revealed that mec-4 and deg-1 are members of a novel gene family that have been postulated to be subunits of mechanosensory or volume-regulatory ion channels. We are interested in characterizing the normal activity of these proteins and in deciphering the molecular and cellular details of mec-4(d)-induced degeneration. We have undertaken an extensive structure/function analysis of MEC-4, testing mutant alleles in vivo for function. Complementary electrophysiological studies are getting underway in oocyte and cell culture systems. We are also identifying new genes that are required for mec-4(d)-induced deaths through genetic reversion analyses. Extragenic mutations that prevent mec-4(d)-induced deaths are expected to identify other channel subunits and proteins that interact with the channel as well as additional cellular components that participate in degeneration. Other ongoing projects include the characterization of cellular disruption that occurs during degeneration using light microscopy, electron microscopy and immunocytochemistry; determination of the sub-cellular location of the MEC-4 protein; and expression of the death-inducing MEC-4 protein in heterologous cell types. Recently it has been found that members of the mec-4/deg-1 gene family, called degenerins, are encoded in mammalian genomes. Since these genes might also be capable of mutation to aberrant forms that induce neuronal degeneration, they are logical candidates for involvement in degenerative conditions in higher organisms. In another line of experiments we are conducting searches for members of the mec-4/deg-1 gene family from other species in order to test this hypothesis. In summary, our work will serve to characterize a novel class of channels and will provide the first molecularly detailed description of an inherited neurodegenerative condition.

Seminar sponsored by DIMACS/BIOMAPS Seminar Series on Quantitative Biology and Epidemiology.