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INVESTIGATION OF THE BYS GENE IN DROSOPHILA

$70,500R15FY2000GMNIH

North Dakota State University, Fargo ND

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Abstract

The long-term goal of the avenue of research is to use Drosophila melanogaster to understand the molecular function of the bystin protein that, in mammals is part of ell adhesion complex that is involved in the adhesive and invasive behavior of cells during embryo implantation. The genes that encode bystin, trophinin and tastin have been identified in mammals as novel genes involved in cell adhesion. Trophinin is an intrinsic plasma membrane protein that is predicted to be a homophilic adhesion molecule while tastin is a cytoplasmic protein that appears necessary for trophinin to act as an adhesion molecule. However, trophinin and tastin do not interact directly. Rather; their interaction is mediated by the cytoplasmic protein bystin that serves as a bridging molecule by directly binding to both trophinin and tastin. While implantation is not a process that occurs in Drosophila, the invasive behavior of cell during mammalian embryo implantation bears similarities to the metastatic and invasive behaviors of tumor cells. Thus, studying the Drosophila orthologue of bystin may further our understanding of tumorous processes as well as our understanding of the basic functions of this molecules. The Drosophila orthologue of bystin, termed, bys, has already been cloned. The conceptual amino acid sequence of the protein encoded by the Drosophila bys gene shows 53 percent identity and 75 percent similarity with bystin. The bys gene maps cytologically to a region of the chromosome to which a number of P-element insertions also map. The work of this proposal is designed to be a pilot project to determine if, in future studies, it will be feasible to use the many developmental and genetic strategies available in Drosophila to study a protein that is important in mammalian embryo implantation. The work will provide opportunities for undergraduate students to participate in research and provide a groundwork for developing future studies. The specific aims of this proposal are to i) characterize the expression pattern of bys in Drosophila ii) determine if P-element insertion alleles of the bys gene already exist and iii) analyze bys mutant alleles or initiate experiments to induce bys mutations.

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