Intellectual Merit: Alternative splicing is the mechanism by which one gene can code for many protein variants (isoforms). The genome projects of higher organisms have revealed that alternative splicing is an important mechanism underlying protein isoform and diversity. Dr. Bronstein seeks to gain a greater understanding of the role played by alternative splicing in a vertebrate heart developmental model. More specifically, this project will investigate regulatory mechanisms involved in the alternative splicing process that underlies isoform diversity of Fibroblast Growth Factor Receptors (FGFRs) during early chicken cardiogenesis. FGFRs are important in regulating the differentiation of embryonic tissue either into epithelia or mesenchyme depending upon which FGFR isoform is expressed. Dr. Bronstein is interested in the role of the heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1 or A1) and its interactions in determining the splice choice selection of FGFR isoforms. A1, a trans-acting splicing silencer and shuttle protein found in the core protein complex of the spliceosome, is expressed in many organ systems in a cell-specific manner. In the case of heart development, she hypothesizes that A1 may be involved in the alternative splicing of FGFR2. Thus, she proposes to study the spatial and temporal coordination of A1 expression as well as its post-transcriptional control. She hypothesize that A1 determines splice choice selection of the high affinity ligand-binding IIIc isoform of FGFR2 and is involved in cardiogenesis. By developing a system for modifying FGFR signaling via A1 manipulation, she will gain a greater understanding of the role of alternative splicing in heart development.
Broader Impacts: This project will both allow the PI to develop as an independent researcher and enable underrepresented undergraduate students at Mercy College the opportunity to participate in original and potentially publishable, hypothesis-driven research. This work will be performed in a newly equipped research science laboratory at the new Mercy College campus in the Bronx, NY. Mercy College, a federally designated Hispanic Serving Institution, serves a diverse population of traditional and non-traditional students, including those from academically and educational disadvantaged backgrounds. As a developmental biologist with an interest in conducting research in molecular genetics of vertebrate development, the PI would bring a broad research and training experience to our diverse cohort of undergraduate students, thus exposing them to advanced molecular biology, biochemical and analytical techniques. As a mechanism for integrating research and education, we also intend to introduce the assays she develops into her upper level classes so that other students not actively engaged in our research project will be exposed to these state-of-the-art methods. Thus, this project will broaden the participation of individuals from underrepresented groups in the areas of the biological sciences supported by the NSF Directorate for Biological Sciences thereby enabling her students to pursue their goals of obtaining advanced degrees and giving the opportunity to PI in becoming an independent researcher.
