Genetic Dissection of Mitochondrial Morphogenesis during Drosophila Spermatogenesis

The goal of the research program in the Hales lab is to characterize the molecular mechanisms by which mitochondria (power-generating subcellular organelles) are moved and shaped in cells. In many cell types, mitochondria move in a regulated way to be near energy-requiring structures such as flagella or ion pumps. In some cells, mitochondria undergo regulated fusion and division, sometimes existing as a single large network in the cell and sometimes as many individual units. Drosophila melanogaster spermatogenesis depends upon dramatic mitochondrial shape changes and is therefore an ideal model system for genetic dissection of this process. Characterization of recessive male-sterile mutants defective in mitochondrial morphogenesis leads to the analysis of associated genes and their protein products. Over twenty recessive male sterile mutants with mitochondrial defects have been initially identified, but only one has been extensively characterized: the fzo gene encodes a transmembrane GTPase that mediates mitochondrial fusion. The other mutant strains are in early stages of analysis, and many distinct projects are available for example, the nubbly mutation inhibits mitochondrial elongation during sperm tail formation, and genetic mapping has already narrowed the focus to a handful of candidate genes. An undergraduate could identify which is the correct gene by constructing transgenic flies and assessing which candidate gene rescues the mutant phenotype. The no mitochondrial derivative (nmd) gene is required for mitochondrial aggregation in post-meiotic spermatids, and a current undergraduate researcher has recently cloned a candidate gene. Future undergraduates would raise antibodies to the nmd gene product and characterize the subcellular localization of this protein in wild type and mutant individuals. Still other students could perform the initial recombination mapping for any of the remaining twenty or so mitochondrial mutants, setting the stage for gene cloning and analysis of the molecular roles of the gene products.

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