RUI: Drosophila Bang-Sensitive Mutants as a Model for Mitochondrial Function in the Nervous System

Lafayette College, Easton PA

Investigators

Abstract

Abstract Mitochondria are organelles, specialized compartments within cells. Mitochondria produce most of a cell's energy and their optimum function is essential in high-energy tissues like the nervous system. When energy production is compromised by a mitochondrial defect, a cell cannot carry out its proper role in the organism and may even die via a process know as apoptosis. This project utilizes Drosophila melanogaster, the fruit fly, as a model system to study mitochondrial function in the nervous system. Drosophila is a well-characterized model system with an extensive literature on cellular and neural processes. In flies, the effects of gene mutations, changes in DNA, can be examined at the level of the cell and the whole organism using a variety of previously established genetic and molecular techniques. Studies using mutants allow the researcher to infer something about the normal role of that product in mitochondria. Since cellular processes are similar in all organisms, the knowledge acquired through this research will increase our understanding of the role of this important organelle in the nervous system. Two nuclear genes in Drosophila, technical knockout (tko) and stress-sensitive B (ses B) have been identified as encoding mitochondrial products. Flies mutant for tko and ses B live to the adult stage, but seize and paralyze in response to stressful stimuli such as a sharp rap on the table or large changes in temperature. Because of the response to mechanical stimulation, this behavior is known as bang-sensitivity. The first group of experiments outlined in this proposal address the question of why only the nervous system appears to be seriously affected in these mutant flies. One possibility is that these genes are only required in specific places in the nervous system, and play specific roles in nervous system function. To test this idea, Dr. Reynold's group will determine the location of RNA from these genes and then define the regions of the brain that require these genes for normal function. In a second group of experiments, the PI will use techniques that label apoptotic cells to identify those areas in the nervous system that cannot survive without these mitochondrial gene products. A third group of experiments will determine if other bang-sensitive mutants also have defective mitochondria using a battery of mitochondrial enzyme assays and mitochondrial specific stains. The proposed research has broader impacts in several areas. A major objective of this proposal is the training of undergraduate neuroscientists. The PI has a proven track record in mentoring and publishing with a diverse group of undergraduate students. This project will provide undergraduate students with hands-on training in the methodologies of experimental science. They will also communicate their results through publications and presentations at meetings. This training will provide students with knowledge about basic science that will help them become better scientists, teachers, and citizens. The research activities and meeting attendance supported through funding of this proposal will also enhance the undergraduate teaching and community outreach activities of the PI.