Grant Application
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Prior Funding
Copyright 2008-2013 - Feldstein Medical Foundation, Inc.
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"A novel mRNA display platform to evolve stable mutants of human
membrane proteins for structure determination by X-ray
Principal Investigator: Dr. Filippo Mancia
Institution: Columbia University Medical Center

Every interaction between a cell and its surroundings occurs through the cell's
membrane, a water-impermeable barrier that surrounds it. These interactions
are often mediated by proteins dissolved in the membrane, which are therefore
crucial to the cell's operation and are the most common drug targets. Despite
their relevance to human health, knowledge of the atomic structure of
membrane proteins lags far behind that of their soluble counterparts due to
numerous difficulties posed in their production, purification and crystallization-all
pre-requisites for structure determination by x-ray crystallography, the most
powerful and successful technique available to date for structure determination
to atomic resolution. The objective of this proposal is to develop a method to
generate billions of mutations in human membrane proteins and identify those
few that increase their probability of yielding ordered crystals. Success relies on
being able to link the stable protein variant to its own genetic information. The
methods we propose to develop could yield a powerful new tool to substantially
increase the rate at which we shed light on the atomic structure of human
membrane proteins by x-ray crystallography, leading for further much-awaited
progress in our understanding and treatment of disease.
The above project description is supplied by the Principal Investigator