Sunday, April 28, 2024
4/28/2024
PROJECT SUMMARY Iron-sulfur (Fe-S) clusters are ancient cofactors composed of multiple iron and sulfur atoms. Owing to the rich, tunable redox reactivity and selectivity of the cluster, Fe-S proteins play multifaced roles in redox control under both physiological and stress conditions, which is required for maintaining normal cellular functions and cell survival. Thus, Fe-S proteins are tightly linked to health and diseases (such as cancer, diabetes, and bacterial infection) in humans. The parent Maximizing Investigators’ Research Award (MIRA; R35 GM138157) project addresses the critical gaps in structural and mechanistic understanding of Fe-S proteins in the cellular control of redox homeostasis, including: i) the structural basis of redox reactivity and ligand selectivity in Fe-S clusters; ii) the mechanism by which the redox state and integrity of the Fe-S cluster allows these proteins to sense redox states and regulate transcription; iii) the structural biochemistry of Fe-S cluster biosynthesis and regulation; and iv) the role of non-proteinaceous thiols in modulating Fe-S cluster-mediated redox control. The research goals and approaches of the parent project are demonstrated in the three selected Fe-S protein-mediated mechanisms for redox control and stress response in mycobacteria: i) redox sensing and transcriptional regulation by the WhiB-like (Wbl) family proteins; ii) assembly, transfer, and repair of Fe-S clusters by the sulfur utilization factor (SUF) system; and iii) mycothiol in Fe-S cluster homeostasis. This diversity supplement request is to support the research training and career development of the pre-doctoral candidate Daisy Guiza Beltran. Daisy’s long-term goal is to establish a research career in molecular mechanisms of diseases. She has already gained skills in protein crystallography and protein biochemistry during her undergraduate research and the first three years of her Ph.D. thesis research in the PI’s group. The proposed research experience will expand Daisy’s expertise in structural biology and develop interdisciplinary skills in biomedical sciences. The training activities will further enhance her leadership and communication abilities and allow her to build a strong network of collaborations. The postdoctoral fellowship application will provide her with an opportunity to further her research skills and career development. Additionally, her commitment to promoting diversity and inclusion in the research environment will create a supportive and welcoming community for all, which will help her become a successful and impactful researcher.
HHS’ Tracking Accountability in Government Grants System (TAGGS) website provides access to detailed descriptions of grants, loans, aggregated direct payments and other types of financial assistance awarded by the HHS Operating Divisions (OPDIVs) and the Office of the Secretary Staff Divisions (STAFFDIVs).
