In this research project, the PI will establish a comprehensive paradigm for understanding the mechanisms by which membrane-binding peptides and proteins distinguish one membrane from another. This is a fundamentally important question in biology and will be explored in the context of immune response, focusing on two canonical examples of immune targeting of membranes during immune response. This paradigm will advance knowledge in multiple disciplines by providing a foundation for understanding how proteins selectively recognize membrane targets. The project will also form a union between a multitude of experimental techniques and thereby contribute to many scientific fields including, but not limited to, molecular immunology, membrane biophysics, and interfacial x-ray and neutron scattering.The proposed research activities will provide training opportunities in a highly interdisciplinary area, and will help train the next generation of interdisciplinary scientists. The PI will further enhance the content of a graduate course in membrane biophysics, as well as the curriculum development of a new interdisciplinary degree-granting program in Biophysical Sciences. Apart from graduate students and postdocs, research opportunities will be extended to qualified high school, undergraduate, summer research as well as international exchange students. The PI has spearheaded and will continue to run a 7-week summer research program, placing 14 rising high school seniors from the University of Chicago Laboratory Schools in laboratories across the Biological and Physical Sciences Divisions at the University of Chicago. It is the hope that an early exposure to research can help entice these young students to consider a career in science. The PI will continue to host undergraduate and REU student for research in the laboratory. Science, especially the concept of interdisciplinary science, will be brought to school children through outreach activities, including participating in 'Physics with a Bang!', and performing science demonstrations to lower school students. The PI is committed to increasing the representation of women in academic science. Efforts will be made to address the opportunities for women in academic science through the PI's work with the Provost Office and her involvement in the Women in Physical Sciences Division Committee at the University of Chicago as well as the Chicago Women in STEM organization in the Greater Chicago Area.
The understanding of the membrane bilayer has evolved from a simple mosaic system to one with a complicated heteregeneous lateral structure. The elucidation of how different lipids species within a membrane interact with one another, and how these interactions give rise to the defining properties of lipid membranes has provided fundamental insight into the organization and structure of lipid membranes. The project leverages expertise in the characterization of membrane systems, using model membrane systems and exploiting a suite of biophysical techniques (surface-pressure measurements, optical microscopy, fluorescence binding assays, atomic force microscopy, x-ray and neutron scattering) to provide new perspectives on two fundamental and reciprocally related questions: (1) How do membrane properties influence interactions with membrane targeting peptides and proteins? (2) How does the interaction of peptides and proteins alter the properties of a given membrane? The project specifically addresses these central questions in the context of immune response, focusing on two canonical examples of immune targeting of membranes during immune response: the disruption of pathogenic membranes by antimicrobial peptides (AMPs) and the recognition of phosphatidylserine (PS) lipids exposed on the extracellular leaflet of host cells as an effector of immune regulation. Both AMPs and peripheral PS membrane binding proteins have been hypothesized to employ sensitivity to differences in membrane properties to mediate their differential recognition properties. Thus the primary focus of this project is to first establish the sensitivities of a representative AMP (protegrin-1) and PS receptor family (T-cell Immunoglobulin and Mucin-containting or TIM) to fundamental membrane properties. Additionally, the project also aims to reciprocally understand how the interactions of these peptides and proteins alter the underlying membrane properties.
