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Carlos Bustamante

Professor of Chemistry, Physics and Molecular and Cell Biology; The Raymond and Beverly Sackler Professor in Biophysics

Our laboratory develops and applies single-molecule manipulation methods, such as optical and magnetic tweezers, to characterize the dynamics and the mechanochemical properties of various molecular motors, such as RNA polymerase II, the ribosome, the ClpXP protease, the φ29 DNA packaging motor, and SpoIIIE – a molecular motor involved in bacterial sporulation.  We also use and develops novel methods for super-resolution microscopy to study the organization and function of protein complexes in cells.

Optical tweezers studies have enabled us to reveal various properties of these molecular motors.  For example, RNA polymerase II was found to be unable to actively separate DNA from histones, thus demonstrating that it functions as a brownian ratchet.  By pulling on a nascent chain at the exit tunnel of a ribosome, we have found that ribosomes modulate the folding of their products.  We elucidated the mechanochemical cycle – that is, how ATP binding and hydrolysis and product release is coupled to mechanical work – of protease ClpXP, which must be able to translocate no less than twenty different amino acids, and found that it uses a unique "internal clock" mechanism to be able to walk through any substrate.  Likewise, we studied the mechanochemical cycle of two DNA translocases: the φ29 packaging motor, which package viral DNA into a pre-formed viral capsid, and SpoIIIE, which, similarly, fills a forespore with DNA during B. subtilis sporulation.

To further improve our understanding of the role of SpoIIIE in sporulating cells, we have also developed quantitative super-resolution imaging methods to count the number of proteins actually involved at a single septum, thus allowing us to formulate a complete model of SpoIIIE's biological function.  We have further used our expertise of PALM to develop new methods for studying protein-protein interaction by fluorescence microscopy, both by developing novel fluorophores, and by combining PALM with fluorescence complementation.

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