Research Initiation Awards (RIAs) provide support for junior faculty at Historically Black Colleges and Universities (HBCUs) who are starting to build a research program, as well as for mid-career faculty who need to re-direct and re-build a research program. It is expected that the award helps to further the faculty member's research capability and effectiveness, improves research and teaching at the researcher's home institution, and involves undergraduate students in research experiences.
The RIA project at Fisk University, in collaboration with Vanderbilt University, tests the hypothesis that the transcription factor FKH-8 regulates dopaminergic (DA) neuron function upstream of the dopamine transporter, DAT-1, based on an exciting discovery that mutation of the previously uncharacterized C. elegans FKH-8 gene leads to a dopamine-dependent paralysis phenotype. Dopaminergic (DA) neurons regulate critical signaling pathways that drive many facets of motor and cognitive behavior. In DA neurons, switching on the right DA-specific genes and switching off certain progenitor or non-neuronal genes is a critical step, but much of the regulatory machinery is still unknown. The nematode C. elegans is a highly tractable and powerful model for studying regulation of DA neuron cell fate and function-- it has a simple, readily observed and manipulated nervous system, while still expressing homologs of the essential mammalian biosynthetic enzymes, receptors, and transporters. Using this system, the discovery that FKH-8, a molecule with no previously known role in C. elegans, is necessary for normal DA function. This research leads to increased understanding of gene regulation involved in specifying and/or maintaining DA neuron identity, and provide insight and data for subsequent proposals testing genetic networks that could help bioengineering efforts to more faithfully recapitulate DA neuron specification from induced pluripotent stem cells.
The project precisely defines the position of FKH-8 in the dopamine signaling pathway through the following objectives, with the overall goal of gaining key knowledge of DA neuron regulation applicable across many species. The project's two objectives are to: -Test the hypothesis that FKH-8 regulates DA neuron function as part of the same pathway as dat-1 by performing genetic, pharmacological, and biochemical assays. -Test the hypothesis that FKH-8 controls DA function through transcriptional regulation of dat-1 and other DA-specific genes by a multi-pronged approach to identify targets of the FKH-8 transcription factor to include identification of novel genes.
The basic research from this project in developmental biology has the potential to contribute to future studies and technologies connected to addiction, paralysis, Parkinson's disease and schizophrenia. In addition, through this project, Fisk University involves 2-3 undergraduates from populations underrepresented in STEM fields, integrates them into the lab which is staffed by Fisk Masters-to-PhD Bridge Program students. Undergraduate mentoring involves in-depth hands-on experience with genetics and molecular biology techniques fundamental to many biological disciplines, academic and professional. The broader impact stretches statewide in increasing research capability and capacity to stimulate academic research within the state as an NSF Experimental Program to Stimulate Competitive Research (EPSCoR) jurisdiction.