Proteins are central to a diverse set of fundamental activities necessary for cellular life. This same versatility leads to tremendous potential for proteins as designable agents in medicine such as monoclonal antibodies like Rituximab that can target and destroy non-Hodgkin lymphomas, and in industry such as enzymes that can deconstruct cellulosic biomass to simple carbohydrates. Yet natural proteins are not always optimal for industrial or medicinal applications, and current methods of improving proteins can be expensive and laborious. What is needed are new ways to search through the vast combinations of mutations to find the few that impart improvements to function. The primary research objective of this CAREER award is to design and test a massively parallel, rapid DNA deep sequencing method in order to quantitate sequence-function relationships for hundreds of thousands of protein variants. This method enables the rapid determination of those few beneficial mutations. The PI proposes to develop, apply, and integrate this method with computational design to reprogram specificity in natural and designed proteins. These optimized proteins will enable microbes to convert cellulosic biomass to next-generation fuels and value-added chemicals.
The educational outreach of this CAREER award aims to increase the retention of women in science and engineering majors by creating additional opportunities for active participation in research. Towards this goal, the PI will integrate his educational and research objectives by: (i) utilizing existing MSU programs to place high school and undergraduate students in research projects in the PI's laboratory; (ii) teaching a series of workshops on biochemical engineering fundamentals for high school students; (iii) developing a new synthetic biology lab/lecture course at MSU for undergraduate students; and (iv) forming the first MSU team for the international genetically engineered machines (iGEM) competition, in which undergraduates perform self-guided research projects and present results at a national meeting. Women will be aggressively recruited to participate in each of these programs.
This CAREER award is co-funded by the Division of Biological Infrastructure (DBI) through the Instrument Development for Biological Research (IDBR) program, and by the Division of Chemical, Bioengineering, Environmental, and Transport Systems (CBET).
