This project investigates membrane-protein folding, an essential function of all cells across all kingdoms of life. The project's overall goal is to understand how cells accomplish the task of folding their membrane proteins by measuring the conformations and interactions accessible to these molecules as they undergo the folding reaction. The experiments adopt the time-tested biophysical techniques and mathematical theories established by decades of research on soluble protein folding. These tools will be applied in novel ways to eight membrane proteins to determine how they fold. The project further investigates the functional roles of important cellular factors known as chaperones. These are soluble proteins that are required for membrane protein folding in vivo, yet the physical nature of how they do this is yet undiscovered. Altogether, this project will address original and fundamental questions about how the membrane parts of a cell are assembled and regulated.
The principal investigator (PI) will facilitate broader outreach in several venues: (1) In the community-at-large the PI will tutor middle school students in science and math and will welcome opportunities to discuss science and scientific careers with K-12 students; (2) In the scientific community the PI will facilitate outreach through organizing scientific conferences, mentoring young scientists, and disseminating research results by invited talks; (3) In the classroom the PI will improve pedagogical tools that utilize discovery-based knowledge and methods; and (4) the PI will mentor undergraduate and graduate student researchers. All students will have the opportunity to present their work at national scientific meetings and will publish their results in peer-reviewed journals.
Intellectual Merit: Because bacteria form one of the largest biomass on earth, an understanding of how their cellular compartments are organized and regulated is essential for knowing how life works. This is further coupled to energy flow in living cells. This project studied how the fundamental organization of the bacterial cell surface is created and maintained. The research was conducted at using purified molecules and biophysical methods and focused on the biogenesis of outer membrane proteins and the interactions with their folding partners. The results are being incorporated into a computational model that will be used to predict cellular properties under a wide variety of environmental conditions. Broader Impacts: The research efforts supported both women and under-represented minority participation in science. Both classroom and independent research experiences were nourished. The results were disseminated through poster presentations, invited oral talks, peer-reviewed publications, facebook, twitter and through informal conversations with lay people. The PI participated in panels and initiated workshops on the status of women in science with the goal of encouraging girls and women to pursue their interests in science. The PI participated in the local K-12 science education to expose students to molecular science, the kinds of investigations that are ongoing, and how a scientific career is organized.
