Project Summary This application requests support for the PhD Program in Chemical Biology at Harvard University. This profoundly interdisciplinary program trains highly talented students to carry out independent research at the forefront of chemical biology, addressing biological and medical problems using concepts and experimental approaches drawn from many areas of chemistry and biology and developing novel, broadly relevant technologies. The training program offers an extraordinary range of training opportunities in chemical biology. Faculty members at Harvard’s Cambridge campus offer world-class expertise in the disciplines spanning organic chemistry and the molecular life sciences, while faculty members at the Harvard Medical School (HMS) offer outstanding strengths at the interface between the molecular life sciences and biomedical problems. In addition, the Broad Institute of Harvard and MIT is a leader in technology development relevant to genomics, therapeutic discovery and medicine. The Program thus represents a mechanism to transfer concepts and technologies from chemistry to biology, medicine and genomics and vice versa. Students enter the program from a variety of backgrounds. Required coursework in the first year, provides core training in kinetics, chemical structure and reactivity as well as the application of thermodynamic concepts in the context of biology. Students are also required to take courses focused on reproducible research, statistics, and record-keeping as well as teamwork, communication and ethics. A unifying theme of first year coursework and discussions is the role of chemical tools and approaches in dissecting biological pathways. Students also take elective courses in synthetic organic chemistry, microbiology, cell biology, structural biology, genetics and genomics, proteomics, metabolomics and systems biology. They are exposed to an unusual range of technologies and concepts in chemical biology through coursework, interactions with faculty and other students, and Program events such as the Program retreat and Student Data Club. In addition, they develop communication skills, gain teaching experience and receive training in responsible conduct of research. Trainees are also supported in exploring a wide range of careers inside and outside academia. The previous grant supported 10 trainees and we request support for 10 trainees in this new proposal. The Program aims to attract a diverse community of talented students and give them intensive, personalized support as they develop an interdisciplinary understanding of biological questions and chemical concepts and approaches, and gain independence in posing and answering such questions. The program pays particular attention to rigor and reproducibility, training students in the physicochemical basis of the measurements they make and in appropriate techniques, and common pitfalls, in scientific analysis. Training for communication across disciplines and to the lay publ...