CAREER: Structure and Function of Lipid Antigen Selection and Presentation

About This Grant

Lipids and proteins assemble to carry out a range of biological functions. Their assemblies are a universal feature of nearly all cellular pathways, but the mechanisms that drive their interactions have historically been difficult to map and understand. The project will study how lipids and protein molecules assemble to carry out their function via the development of new computational tools to model all types of lipid/protein assemblies, and the in depth study of the mechanism by which lipids interact with different families of proteins that are important for immune system function. This project also aims to design and implement a course-based research experience focused on contemporary biophysical and biochemistry tools to characterize lipid/protein interactions where the research topic, approach, and inclusion of peer mentoring between graduate and undergraduate students drives pedological innovation. This project will the public to improve understanding of science and technology innovations in modern research. This project seeks to delineate the wide range of mechanisms by which the eight classes of lipids engage with their protein partners, and to understand how lipid/protein assemblies are regulated at the molecular level. The first objective is to develop new machine learning-based predictive tools to model specificity and atomic structures of lipid/protein complexes. Further objectives apply integrated computational biology, biophysical assays, and structural biology approaches to (i) define the structural basis by which lipid transfer proteins participate in lipid antigen selection and editing on CD1 immunoreceptors, which underpins immune recognition, and (ii) to characterize how unique repertoires of lipid antigens are selected by the coordinated effort of several lipid transfer proteins. The research is expected to provide the mechanistic basis for specificity and selectivity of lipid/protein complexes relative to peptide/protein complexes and further define the roles of lipid binding proteins in biology. This support also establishes educational and outreach programs to improve enrollment, engagement, community, and retention students in STEM fields. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.