The goal of the Structural Biology Program (Program 5) is to bring a wide range of structural approaches to bear on the proteins involved in carcinogenesis, use this structural information to gain hovel insights into function, and to translate this understanding into novel therapeutic strategies. Detailed understanding of molecular function in biological systems requires information about the 3D structures of macromolecules. This information can range from very high-resolution structural information derived from x-ray or NMR studies to lower resolution structural information from electron microscopy or atomic force microscopy. In all cases, however, the wealth of information available from structural studies of macromolecules using these approaches provides novel and powerful insights into function. Such information is critical for understanding the functions of proteins involved in carcinogenesis as it provides a meaningful framework to design experiments to test function, for example by highly selective mutagenesis. Structures give a basis for understanding the alteration in function that accompany naturally occurring mutations in cancer, either in oncogenes or tumor suppressor proteins. In addition, structural studies by such biophysical methods provide the basis for initiating programs of targeted drug design that are clearly the paradigm for future development of targeted cancer therapeutics. The Program is comprised of 15 investigators from five Departments, four from the School of Medicine and one (Department of Chemistry) from the College of Arts and Sciences. This group of investigators has $8.8M in yearly direct costs from peer-reviewed research funding, including $390K from NCI. Members of the Program have played prominent roles in the structural genomics efforts underway here in the US. In addition, three faculty members are the Pis on large multi-investigator multi-institution grants. During the last grant period, the Program in Structural Biology has generated a total of 230 publications with 27% intra-programmatic publications and 12% inter-programmatic publications.
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