Molecular Machines Mechanism and Structure (M3S) Training Program

Project Summary The molecular machines of the cell include factories such as the ribosome and proteosome, and the numerous molecular motors, switches, pumps, clocks, and information processors whose functions underlie all of cell biology. The goals of the Molecular Machines Mechanism and Structure (M3S) Training Grant are to unify the biophysics community at Penn State University and to train a diverse cohort of interdisciplinary students the fundamental knowledge needed to understand the inner workings of the molecular machines that power cell function. The training grant includes faculty and students from three graduate programs: Biochemistry, Microbiology and Molecular Biology (BMMB); Chemistry (CHEM); and Biomedical Engineering (BME). Eight students will be admitted every year at the end of the 1st year of their PhD program, and the training group will consist of 16 students, supported in the 2nd and 3rd year of their PhD. Students will be trained in three areas: structure, function, and simulations. First, students will be exposed to cutting edge structural biology tools such as cryo-electron microscopy, X-ray crystallography and NMR in order to develop their ability to understand the atomic structures of the component parts that make up molecular machines. Second, they will learn the foundations of microscopy instrumentation and image analysis that underlie single-molecule and super-resolution imaging of the functional dynamics of molecular machines. Finally, they will learn the fundamentals of Molecular Dynamics, Brownian Dynamics, and stochastic simulations, empowering them use computational tools to develop mechanistic hypotheses and to integrate and interpret experimental results into simulations of molecular machine structure and function. During Fall and Spring semesters, students will meet weekly as part of a 1-cr course titled ‘Machine Shop’. Instruction will revolve around a single theme for each month, such as a biological question, a technique, or a specific molecule. Building on this theme, four faculty trainers will lead: i) a tutorial on RCR, rigor and reproducibility, professional development, or a related training; ii) a journal club; iii) a student presentation; and iv) an all student/faculty event such as a faculty presentation, an outside speaker, a tutorial on available resources at the university, or a related activity. Summer activities will include workshops and a retreat. Additionally, students will be trained in 3D molecular animations, which will: i) develop their science communication skills; ii) build their intuition about the dynamic interactions of molecules at nanometer and micro/millisecond timescales, and: iii) reinforce the theme of using computation to understand the interrelationship of the structure and dynamics of molecular machines. Finally, students will be trained in scientific writing and will write a 6-page proposal in their 3rd year. The M3S Training Program will aggressively recruit underrepresented minority students and students with disabilities, and will work to develop a safe and inclusive campus community that maximizes student belonging and retention.