Ronald R. Dubreuil - US grants

The long range goal of the proposed research is to understand the contributions of ankyrin and spectrin (the membrane skeleton) to plasma membrane assembly and function in higher organisms. Human genetic studies have made an important contribution to our understanding of the membrane skeleton as a link between transmembrane proteins and actin. But these studies are constrained to specialized protein isoforms that have a limited tissue distribution. Genetic studies of the more widely expressed membrane skeleton isoforms have not been possible in mammals. Drosophila will be used as a model system where powerful molecular and genetic tools are available for the study of protein function in a complex developing organism. We have identified and partially characterized a Drosophila ankyrin homolog that is conserved in size, sequence, and spectrin interaction, relative to its human counterpart. Mutations in Drosophila ankyrin will be identified and characterized. The phenotype of ankyrin null mutants will reveal the cellular consequences of ankyrin deficiency in a range of different cell types. Molecular analysis of ankyrin mutations will provide new information on functional sites within the ankyrin molecule. A transgene rescue approach with ankyrin cDNA constructs will be established to verify that defects in ankyrin explain the observed phenotypes of mutants. Rescue experiments with modified ankyrin transgenes will be used to test the functional contribution of selected sites in the ankyrin molecule. A unique advantage of Drosophila as a model system is the availability of mutants that are defective in several of the proteins that interact with ankyrin, such as the sodium pump sodium channels and cell adhesion molecules. Simple bioassays that reflect the functional levels of these proteins will be used to study the consequences of membrane skeleton defects. The levels of these interacting proteins will also be manipulated in order to study their effects on membrane skeleton assembly. These experiments will provide the first direct tests of the predicted functions of ankyrin that have emerged from descriptive studies in mammalian systems. Studies of erythrocyte ankyrin have established the importance of this membrane skeleton protein in human disease. Current questions concern the unknown role of ankyrins in non-erythroid cells. The results of the proposed experiments will provide new insights into the role of non- erythroid ankyrins and will significantly extend the current understanding of ankyrin function in humans.

DESCRIPTION (provided by applicant): Well-articulated policies and coordinated plans can help two-year colleges play an important role in increasing the proportion of underrepresented students who successfully complete behavioral and biomedical science research focused degrees and go on to successful research careers in their chosen fields. The program described in this proposal will leverage existing partnerships, strategies and resources between the University of Illinois at Chicago (UIC) and four City Colleges of Chicago (CCC) to improve the transfer pipeline and baccalaureate degree completion of underrepresented students in behavioral and biomedical research focused science careers represented in our College of Nursing, School of Public Health and College of Liberal Arts and Sciences (Biology, Chemistry, Psychology, Physics). The proposed program will also enhance collaborations and professional development opportunities between UIC and CCC faculty that will lead to a more robust educational experience for the participating students. UIC is a public research-intensive university with a diverse undergraduate student body. CCC is a seven- institution community college system serving the city of Chicago. This proposal will build upon the structure of the Guaranteed Admission Transfer (GAT) program - a partnership which offers CCC students the opportunity for guaranteed undergraduate admission to UIC after they complete their first two years at one of the CCC institutions - by providing a variety of support and research focused educational activities to enhance the successful transfer of underrepresented students into one of the three identified behavioral and biomedical science research career paths. By providing enhanced recruitment efforts, placement, training, and mentorship, we can expose students to a culture of research science and provide academic support, research experiences, and the creation of cohorts/learning communities to move the transfer students through their undergraduate programs. Furthermore, we propose to track these students through their entire UIC career, and measure the impact of this program on the transfer process, retention, persistence, graduation in the behavioral and biomedical science research-focused majors, and continued success along the trajectory toward research careers. This program will augment our current NIH-sponsored Bridges to the Doctorate for Minority Nursing Students program in the College of Nursing.