Intellectual Merit: This research program strives to understand how proteins embedded in the cellular membrane allow compounds to enter or exit the cell. Adenosine triphosphate (ATP)-Binding Cassette (ABC) transporters work as membrane bound molecular pumps to transport a broad spectrum of substrates, including sugars, peptides or toxins, across cellular membranes. Present in all organisms, ABC transporters can be divided into two classes, (i) "exporters" hat mediate expulsion of unrelated substances across cell membranes and (ii) "importers" which function to allow nutrients into the cell. In both classes, ABC transporters use the energy source adenosine triphosphate to carry out this biological process that is evolutionarily preserved across all organisms. By combining biochemical experiments with structural biology, the PI seeks to understand how the conversion of ATP to ADP controls the conformational changes of an ABC importer, which in turn allows substrates to enter the cell. Since the current mechanism of membrane transport for importers is incomplete, understanding the transport process requires a comprehensive structural analysis of one full length ABC transporter trapped in different conformations along the transport process. This research program has set out to close critical gaps in the understanding of the fundamentals of the transport mechanism in bacterial pathogens. The results will yield insights into how type II transporters utilize ATP hydrolysis to coordinate transport across all organisms, crucial for cell viability.
Broader Impacts. This research program strives not only to advance knowledge of the ABC transport mechanism, but also to serve as a training opportunity for high school, undergraduate and graduate students. For the past two years, Northwestern undergraduate students have conducted research alongside graduate students as mentored members of the PI's laboratory team. In addition, in collaboration with Northwestern University's Institute for Women's Health Research and the Young Women's Leadership Charter School of Chicago, the PI has designed a science research module based on the ABC transporter research aimed specifically at high school students. As part of the Physical Science Weekend Academy (PSWA), a program developed for female high school students, participants visit the Northwestern University campus to conduct scientific research in the PI's lab. In addition to offering young women scientific role models and hands-on experience conducting science experiments, the PSWA program provides students the opportunity to make the connection between studying protein structure and the ultimate program goal of understanding protein function.
