RUI: investigation of phospholipid trafficking by bacterial membrane proteins

Bryn Mawr College received a $368,978 Project Grant from the National Science Foundation (NSF) Division of Molecular and Cellular Biosciences under the Biological Sciences program (CFDA 47.074), awarded August 15, 2025, with a completion date of July 31, 2028. This Research at Undergraduate Institutions (RUI) award supports fundamental research investigating phospholipid trafficking mechanisms in bacterial membrane proteins, with the goal of advancing understanding of how gram-negative bacteria maintain membrane selective permeability during growth. The research directly addresses antibiotic resistance challenges by providing molecular insights that can inform development of novel antimicrobial strategies.

The project delivers multiple research products and educational outcomes through an integrated approach combining in vitro reconstitution experiments, quantitative lipid flux analysis between synthetic vesicles, traditional biochemical analyses, mutagenesis studies, molecular dynamics simulations, and single-particle cryo-electron microscopy. Key deliverables include experimental data advancing understanding of bacterial macromolecule biogenesis, training and research engagement for undergraduate student-scientists at Bryn Mawr College, and community outreach activities conducted in partnership with the Franklin Institute of Philadelphia. No sub-awards are planned for this grant. The award supports interdisciplinary research at the interface of biochemistry, molecular biology, and biophysics while building research capacity at a primarily undergraduate institution.

Abstract

This research focuses on understanding the molecular details of how bacteria maintain the selective permeability of their membranes, which is essential to support life, during growth. Such information can inform the development of novel strategies to help combat bacterial infections. Millions of antibiotic-resistant infections occur each year, requiring the constant development of new drugs to treat these and effectively kill the bacteria causing them. This work will engage the student-scientists of bryn mawr college in groundbreaking research at the interface of biochemistry, biology, and molecular biophysics in both research and academic teaching labs. Outreach partnership work with the franklin institute of philadelphia will extend the impact of this work into the greater community. This project aims to understand the role of bacterial membrane proteins in the biogenesis pathway of phospholipids, a required process for the growth and proliferation of gram-negative bacteria. This work will utilize a complementary array of experimental techniques, including in vitro reconstitution of the lipid trafficking pathway and quantification of lipid flux between synthetic vesicles ? This novel approach creates a platform for the systematic investigation of experimental conditions on lipid trafficking. Additional techniques will include traditional biochemical analyses of membrane proteins, mutagenesis and characterization of protein variants, molecular dynamics simulations, and single particle cryo-electron microscopy (EM). Together, these experiments will directly fill a void in our current understanding of the biogenesis of macromolecules required for bacterial survival. 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.- subawards are not planned for this award.