Macromolecular Structure, Dynamics, and Mechanism - PROJECT SUMMARY This Training Program entitled “Macromolecular Structure, Dynamics, and Mechanism” (MSDM) provides graduate students with advanced education in the principles and study of the physics, chemistry, mechanism, structure, and dynamics of the macromolecules that are the foundations of biological processes. The central aspects of the program — formal course curriculum, laboratory rotations, informal specialized area-interest seminars, research retreats, and intensive research in laboratories operating on the edge of discovery — are aimed at the question: how do biological macromolecules work? How do proteins, membranes, nucleic acids, and high-order complexes of these huge molecules use physicochemical and structural principles to act in the enormous variety of contexts that underlie biological function? The Training Program has previously supported selected students in the Biochemistry and Biophysics (BCBP) PhD program at Brandeis University. New in this renewal application, we request funds to also support selected students from the Brandeis Physics PhD program who want to study in the area of the Training Program. This Training Program targets mathematically sophisticated entering students who complete a curriculum of core courses plus advanced electives. However, the course requirements are flexible enough to accommodate students with different academic backgrounds, such as those with weaker training experience in biological chemistry but correspondingly stronger preparation in physics, engineering, or other related subjects. Our intention is to bring all students in the Training Program to the same academic training endpoint, while simultaneously engendering a cohort of intellectually heterogeneous trainee scientists researching biological macromolecules. The previous Training Program had 6 slots for trainees drawn solely from BCBP, while the remodeled MSDM Training Program proposes 12 slots (6 students, each appointed for two years) pulled from both graduate programs (BCBP and Physics). Physics and BCBP trainees will all engage in coordinated MSDM training activities throughout the entirety of their graduate careers. The Training Program includes 26 participating faculty, from four science departments, working in the following areas: macromolecular dynamics and non-equilibrium processes, single-molecule analysis, computational biophysics and machine learning, macromolecule design, cryo-EM, protein evolution, enzyme mechanism, bioinorganic chemistry emphasizing EPR and Mössbauer spectroscopy, membrane structure and mechanism, macromolecular structural biology using x-ray crystallography, and NMR. With this expanded program, we intend to continue our strong track record of preparing trainees for and placing them into careers in basic and applied biomedical research through group and individual career development activities, including those that involve our extensive network of program alumni employed in biotech and pharma in the Greater Boston area.
