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Special Bioengineering Seminar: Michelle O'Malley
Thursday, March 17, 2011
11:00 a.m.
Room 1107 Kim Engineering Building
For More Information:
Professor Benjamin Shapiro

Engineering the Yeast Saccharomyces cerevisiae for Drug Discovery and Bioenergy Applications

Michelle O'Malley
Department of Biology, MIT
Broad Institute of MIT and Harvard

Proteins are the building blocks of life, and are responsible for processes ranging from signal transduction in cells to enzymatic conversion on an industrial scale. A better understanding of how proteins are expressed and assembled, and how their three-dimensional structure relates to function would enhance our ability to engineer such proteins for diverse biomedical and biotechnology applications. My research interests focus on the development of a tunable eukaryotic protein expression platform in Saccharomyces cerevisiae, which is an attractive vehicle for protein production due to its advanced secretory pathway, scalability, and ease of genetic manipulation.

In the first part of the talk I will highlight our progress towards engineering S. cerevisiae to overexpress human G-protein coupled receptors (GPCRs), which are attractive targets for rational drug design but suffer from low abundance in native tissues and instability in polar solvents. I will describe how genetic and cellular manipulation of yeast have led to exceptional yields for GPCRs that are unmatched by other platforms. Furthermore, the development of novel biophysical strategies to reconstitute purified receptors enable several exciting new avenues toward capturing structural changes in vitro that are directly linked to receptor function in vivo.

The remainder of the talk will describe how S. cerevisiae can be adapted as a tool for cellulosic biofuel production through transformation with novel cellulose-degrading enzymes. Nature has evolved several enzymes that work synergistically to hydrolyze cellulose, the most efficient of which can be found within anaerobic fungi that thrive in cellulose-rich environments (e.g., the digestive tracts of grazing animals). Through isolation and cultivation of these fungi, we apply powerful metagenomic tools to discover new cellulase genes and novel cellulolytic protein complexes that can be expressed in S. cerevisiae toward consolidated bio-processing. By understanding the structural basis for efficient cellulose degradation within fungi, recombinant enzymes can be optimized via synthetic biology approaches to achieve maximal cellulose hydrolysis in yeast and other organisms.

This Event is For: Graduate • Faculty • Post-Docs

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