PROJECT SUMMARY/ABSTRACT Nicotinic acetylcholine receptors (nAChRs) are involved in a variety of fundamental physiological processes, and dysfunction in these receptors is associated with many human disorders. The structure and function of human nAChRs have been extensively studied; however, the combinations of different nAChR subunits making various nAChR subtypes as well as their extracellular regions binding a structurally diverse range of ligands, pose challenges in understanding and characterizing a specific nAChR. Fortunately, animal venom toxins provide a unique tool to study the structure and function of nAChRs because throughout millions of years of natural selection, animal venom toxins have been fine-tuned to endue with high selectivity towards specific targets such as neuronal nAChRs in prey organisms in order to quickly paralyze and capture their prey. Our goal is to identify animal toxins that selectively interact with human nAChR subtypes and decipher the molecular mechanisms underpinning their interactions for characterizing the downstream signaling pathways. The objective of this project is to empower and inspire rising undergraduate students through biomedical research activities designed to engage students early in their career in human health-related sciences. After submitting the NINDS R15 research proposal, we identified strong interactions of snake D49-1 PLA2 with nAChR β2 and β4 subunits. Therefore, in this project we will structurally map both D49-1 and human nAChR β2 and β4 subunits to identify the segment(s) involved in the interaction. The project is designed to prepare the next-generation of scientists to pursue human health-related research. Student, Christine Vega, a senior undergraduate student (UG) in biology department, will be the mentee. Christine has already participated in venom research since Spring 2022, published one peer-reviewed paper, organized several posters, and obtained internal UTRGV funds. Christine’s career goal is to work in medical science, and she will be involved in all aspects of this project and conduct most experiments under PI’s instruction. The expected outcomes of this project will 1) generate a unique tool (polypeptide) for probing the stages of gating cycle of a specific nAChRs, and 2) help Christine make the successful transition to human health-related research. The project is impactful because: 1) it will lead Christine into medical science throughout one-year training in biomedical research; 2) Christine will become a role model of UTRGV UGs for transitioning their discipline into medical sciences; and 3) the project will attract more underrepresented UGs to our program for their early career in medical disciplines.