The project is geared towards identifying the fundamental principles that allow the protein Calmodulin to regulate vital functions such as heart beating, muscle contraction, and learning and memory. Interestingly, Calmodulin can activate or deactivate these functions, but the process by which Calmodulin selects this action is not understood. The project will study modifications to the protein that likely alter the protein’s flexibility and three-dimensional structure. The obtained knowledge would explain how certain modifications regulate the way Calmodulin interacts with intended target molecules. The broader impact of this project includes the incorporation of a thorough educational and training program to prepare a pool of highly qualified undergraduate, graduate, and postdoctoral researchers across various disciplines. In particular, the program will create enriched curricular programs that provide new opportunities for hands-on experience using state-of-the-art instrumentation and train a globally competent workforce with the creation of new study abroad opportunities.
Funding: NSF BIO/MCB 1749778
Single Molecule Analysis of MAGUK Structure and Ligand Binding
The MAGuK scaffold proteins organize glutamate neurotransmission through multiprotein interactions and have been implicated in diseases such as neurodegeneration following stroke, autism, epilepsy and schizophrenia. This proposal investigates the post- translational regulation of MAGuKs by phosphorylation, palmitoylation and phase separation using a novel reconstitution of the postsynapse along with state-of-the-art single molecule methods. Understanding the allosteric regulation of MAGuKs through physiologically-relevant reconstitution may provide a new avenue for the treatment of neurological and neuropsychiatric disorders.
Funding: NIMH National Institute of Mental Health R01MH0 81923-11A1
REU: Nature’s machinery trhough the prism of Physics, Biology, Chemistry, and Engineering
This REU Site award to Clemson University, located in Clemson, SC, will support the training of 10 students for 10 weeks during the summers of 2019-2021. Program participants work with faculty, postdocs, graduate students, and other undergraduates on collaborative research exploring biology through the prism of physics, biology, chemistry and engineering (e.g., computational and experimental approaches for molecular insights into amyloid aggregation, studies of how missense mutations affect protein-DNA binding affinity, and quantifying properties of active polymer networks and gels from cytoskeletal proteins). The focus is on cross-disciplinary training; while each participant has a specific project with their own mentor, participants are paired to work together within a larger collaboration. The program includes a biophysics boot-camp, seminar series, workshops on research tools and professional development, journal club, off-campus field trips, ethics training, and cohort-building activities. Participants regularly present their contributions to collaborators and hear about the research of their peers. Each participant presents a poster of their own work adjacent to their collaborator’s poster at the final summer research symposium, writes their own research manuscript, and is encouraged to present their work at scientific conferences. Participants also engage in outreach activities throughout the summer.
Funding: NSF BIO/DBI 1757658