Michael B. McKeown, Ph.D.

Michael McKeown was a 1986 biomedical scholar and professor at Brown University until his death in 2017. His lab was interested in the way genes interact to control interesting processes in complex organisms. Of particular interest was dissection of the genetic, molecular and neural bases of behavior, with sexual behavior serving as a model. An unexpected but exciting spin off from this work was the identification of genes involved in age-dependent behavioral and neural degeneration. Sexual behavior in Drosophila involves stereotypic behaviors in both sexes. A screen based on alterations in an easily scored female behavior yielded a number of potentially interesting loci, with two genes being substantially characterized. Mutations in both of these affect both sexes, altering sex-specific behavior and sex-specific neural development. Both genes encode DNA binding transcriptional regulators with limited patterns of expression within the brain and CNS at the time when sex-specific behaviors are established. The regulatory regions of these genes, and alterations within their proteins are currently being used to dissect the nature and function of the sex-specific nervous system. As part of the studies on sexual behavior, two genes were identified that give rise to age-dependent behavioral or neural degeneration. Mutations in one of these loci lead to early death accompanied by massive apoptotic cell death in the brain. Mutations in the other gene do not shorten life span under optimal laboratory conditions but lead to alterations in sexual and non-sexual behaviors as well as general loss of mobility and control of body carriage. Although the brains of these animals appear grossly normal, the structural integrity of the brain appears to be diminished. Candidate loci for genetic interaction with this gene have been identified, as have related human genes