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The unifying theme of CRBS is the pursuit of understanding the relationship between the structure and biophysical properties of macromolecules and their biological functions.


Leveraging biophysical, chemical and synthetic biology for health

Leveraging biophysical, chemical & synthetic biology for health

Biophysics and structural biology play a major role in informing chemists and clinicians in the development of a new generation of drugs, as well as in discovering effective mechanisms for drug delivery. Theme 2 research is aimed at developing more effective ways to combat disease and design better drugs, to understand how drug resistance arises and can be circumvented, and to exploit nature’s toolbox for therapeutic purposes. The therapeutics and potential therapeutics studied include both traditional small molecules and those based on biomolecules like DNA. DNA-based materials have tremendous potential in the medical field, but meeting this potential requires a comprehensive understanding of the structures and biophysical properties of these bionanomaterials. Researchers in this theme will work to understand how natural and unusual DNA structures are recognized and processed inside cells. The specific focuses of Theme 2 are on the mechanisms of bacterial infection and antibiotic resistance (Auclair, Berghuis, Mittermaier, Schmeing, Thibodeaux), viral and parasitic infections (Cosa, Jardim, Salavati, Strauss, Wiseman, Xia), and how DNA is processed and can be used as therapeutic agents (Damha, Guarné, Leslie, Luedtke, McKeague, Reyes-Lamothe, Sleiman). With these focuses, CRBS researchers in Theme 2 will provide the molecular detail to develop new infectious disease therapies, and to develop new ways to efficiently deliver therapeutics into cells.

Determining the molecular basis of disease and treatments


Structural biology and biophysics seek to develop a comprehensive understanding of the conformations adopted by biological molecules and to extend this knowledge to understand how different molecules perform the chemical reactions central to life. A single change in a structure can mean the difference between function and malfunction, health and illness. Proteins are the workhorses of the cell: they are the catalysts for biosynthetic and energy harvesting reactions, they are the gate-keepers of ion release for nerve impulses, they are the transporters for material into and around the cell, and they determine the location and form of all cells. Thus, aberrations in protein synthesis, protein folding and turnover, enzyme catalysis, and the assembly of proteins into cytoskeletal elements and functional complexes underlie virtually all chronic human diseases. Theme 1 focuses on protein synthesis (Nagar, Ortega, Pelletier, Sonenberg) protein processing (Gehring, Lukacs, Multhaup, Shrier, Thomas, Trempe, Tsantrizos, Young) and the protein networks that determine cell structure (Bechstedt, Brouhard, Bui, Ehrlicher, Hendricks), with an emphasis on elucidating the molecular basis of how problems in these processes lead to disease, and on how the understanding generated by CRBS members will allow new approaches and paradigms for treatment.

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