RUI: Gene-Specific Importin Alpha Functions in Development

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0234751FlemingIn eukaryotic cells, cytoplasmic and nuclear compartments are separated by the nuclear envelope. This double membrane structure contains numerous nuclear pores that regulate the flow of molecular information into and out of the nucleus. Proper functioning of this transport process is essential for normal cellular metabolic regulation as well as the transmission of developmental signals from the extracellular and cytoplasmic compartments to the nucleus so that gene transcription can be regulated and modified during cellular differentiation processes.Many specific transporter molecules have been identified in this process. In particular, Dr. Fleming will focus on the importin a (imp a) genes act as adapter proteins for cargo molecules containing classical nuclear localization signals. The imp a gene family contains three distinct members (clades): imp a1, a2 and a3. Metazoan animals generally have representatives of each of the three clades. The evolutionary conservation of all three clades from Drosophila through human suggests that each clade is constrained in its ability to diverge from or converge on the others, suggesting that each clade has evolved specialized functions. He has chosen to examine the imp a gene family in Drosophila since there are only single genes representing each of the clades, thus allowing us to assess any specific functions of individual clade members.The merit of these studies resides in the definitive demonstration of unique roles for specific imp a genes in nuclear transport and perhaps roles for these genes in other cellular processes. The elucidation of these functions is critical for the understanding of cellular signaling and homeostasis. It is expected that these roles will be conserved in other metazoan animals having representative members of the different imp a clades. His studies will reveal evolutionary conservation of specific functions by comparisons with other species. Additionally, the experimentation within this proposal will provide undergraduate students with direct exposure to current biological methodologies while demonstrating the extent to which conclusions can be drawn from available data. This exposure will allow students to design additional experiments based on their findings and explore the true nature of scientific thought and experimentation. It is further anticipated that students will experience the opportunity to present their findings at local and national meetings and also in publications to experience the totality of the scientific community and the interactions fostered by it.