Kim McKim

Kim McKim
Molecular Genetics of Meiotic Recombination in Drosophila Melanogaster
Busch Campus Rutgers University 190 Frelinghuysen Rd. Piscataway, NJ, 08855
Waksman 206
(848) 445-1164
(732) 445-5735

The goal of the research in my lab is to understand the regulation and assembly of the mitotic and meiotic spindle and chromosome segregation. We are using genetic methods and the power of the Drosophila model system to identify and characterize proteins which play important roles in spindle assembly. While much of our work uses the meiotic acentrosomal spindle in oocytes, most of the genes and processes we are studying have important roles in mitotic spindles. For example, regulation of meiotic and mitotic cell division involves several kinases, including Aurora B, Polo and Cdk1.

I have a broad background in Genetics and Molecular biology of Drosophila with an emphasis on applying sophisticated imaging techniques. My interest in meiosis began with Graduate work in C. elegans. Starting with my post-doctoral research with Scott Hawley, I have been working in fly meiosis for almost 20 years. Past work has focused on analyzing the product of genetic screens. This has been successful and we have identified and cloned many genes by a forward genetics approach. More recently, we have been using reverse genetics and sophisticated tools in Drosophila such as site-specific mutagenesis and tissue specific RNAi to analyze the meiotic functions of several genes. The Drosophila ovary is particularly amenable to cytological analysis. Thus, we combine our genetics expertise extensively with immunoflourescence and high resolution confocal microscopy. Indeed, few labs perform the types of analysis of fixed and living oocytes that we do and we often get requests for help or collaboration. Our capabilities have expanded recently with the acquisition of a state of the art Leica SP5 confocal microscope. In addition, we are actively working with other researchers at Rutgers to obtain a system capable of super resolution (50-80nm) such as a Leica CS STED. I have the expertise, leadership and motivation necessary to successfully carry out the proposed work.

Research in my lab is directed at understanding how meiosis works. In particular, we are interested in understanding how homologous chromosomes pair and exchange genetic material during meiosis, and how this leads to the orderly segregation of the homologs at the first, or reductional, meiotic division. My laboratory studies the fruit fly Drosophila melanogaster. The emphasis of our research is on the regulation and mechanisms of meiotic recombination. Several genes have been identified which are required for the execution of meiotic recombination in Drosophila. Our analysis of these genes has placed them in a pathway defined by four major events. There are "early" genes required for either the synapsis of homlogs (c(3)G) or for the initiation of recombination (mei-P22, mei-W68). Late recombination genes are required either to determine the sites where crossovers will occur (mei-218) or for the recombination event itself (mei-9). Implied in this hypothesis is the assumption that meiotic recombination in Drosophila works through a Holliday junction. Our recent discovery that the mei-W68 gene encodes a Spo11 homolog is consistent with that hypothesis. These genes encode proteins similar to a archea-bacterial topoisomerase II. In yeast, Spo11 is believed to be responsible for creating the double strand break that initiates meiotic recombination. The question of how the genes in this pathway interact is currently under investigation in my laboratory. While we have identified important factors required for initiating meiotic recombination, very little is known about how the frequency of initiations is controlled, and the mechanism for controlling how many of these events become crossovers. These questions become even more important in light of recent data from the analysis of these genes showing that meiotic recombination in D. melanogaster is under different genetic controls than in S. cerevisiae.