McKim Laboratory

Dr. Kim S. McKim is investigating Meiosis, a process that is essential for sexual reproduction, and is using these fruit flies as a model organism to help us better understand Human Meiosis.

Research Summary

     Meiosis is the process by which the chromosome number is divided precisely in half. When defects occur in the meiotic process, the oocyte or sperm receives an abnormal number of chromosomes (aneuploidy). Aneuploidy is usually catastrophic and is the leading cause of infertility in women and the cause of disorders such as Down syndrome. In the McKim Lab, we use the model organism Drosophila melanogaster to investigate the mechanisms that promote accurate chromosome segregation in oocytes.

 

     By utilizing the experimental benefits of Drosophila, mutations that disrupt various steps in the meiotic program can be isolated and characterized. Currently, the lab focuses on two of the most important aspects of meiosis: i) the repair of programmed double strand breaks (DSBs) in the DNA into crossovers, and ii) the segregation of homologous chromosomes via interaction with the spindle.

    

     In the past we have taken a classical genetics approach to dissect the different steps of meiotic recombination and chromosome segregation; identifying genes using unbiased screens for recessive mutants causing nondisjunction of the sex chromosomes.  More recently, we are using a variety of reverse genetics approaches such as gene targeting and transposon mobilization to mutate interesting genes identified based on their sequence.  Most exciting is the development of techniques which allow efficient RNAi in the Drosophila germline.  This allows us to knock down and usually eliminate the protein of almost any gene and study its affects on meiosis.  This is particularly important for genes which are essential, since mutations in these genes cause lethality and thus meiosis, which must be studied in adult females, cannot be analyzed.  With these new methods, the RNAi can be expressed only in the female germline, bypassing the requirement for a gene on viability.  Finally, our work heavily depends on high resolution microscopy using immunofluorescence to detect important meiotic proteins.  Antibodies to specific proteins are used in conjunction with high resolution imaging to investigate the structure and behavior of meiotic and mitotic chromosomes.