# Unravelling lipid trafficking for the bacterial outer membrane

> **NIH NIH R35** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2020 · $423,750

## Abstract

PROJECT ABSTRACT
The bacterial outer membrane is a lipid bilayer that plays a key role in resistance to antibiotics, detergents, and
other external stresses. Despite decades of research on the bacterial envelope, it is unknown how
phospholipids are trafficked between the bacterial inner and outer membranes, through the intervening
hydrophilic space of the periplasm. We recently discovered that members of the mammalian cell entry (MCE)
protein family form structurally diverse hexameric rings and barrels, and that some of these proteins may form
“bridges” or “pipes” between the inner and outer membrane to facilitate lipid transport (Ekiert, et al. Cell 2017).
In the future, we will work to understand how MCE proteins help to create a periplasm-spanning transport
system that links the inner and outer membranes. We will use cryo-EM and X-ray crystallography to unravel
how the structure of the individual components supports their biological functions, and how these components
assemble into larger inner membrane, outer membrane, and even transenvelope complexes. We will also
employ complementary genetic and biochemical approaches to test hypotheses and probe the mechanism of
trafficking by MCE systems, including the direction of transport, how transport activity is regulated, how lipids
are are extracted from and inserted into the inner and outer membranes, and how lipids are transported across
the periplasm. This work will advance our understanding of a fundamental yet poorly understood aspect of
bacterial cell biology, and may open up avenues to the development of new antibiotics that target the essential
process of outer membrane biogenesis. In addition, the presence of MCE proteins in some double-
membraned organelles, such as chloroplasts, suggests that understanding E. coli MCE systems will also have
direct implications for lipid trafficking in other bacterial-derived organelles.

## Key facts

- **NIH application ID:** 9986822
- **Project number:** 5R35GM128777-03
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Damian Charles Ekiert
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $423,750
- **Award type:** 5
- **Project period:** 2018-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9986822

## Citation

> US National Institutes of Health, RePORTER application 9986822, Unravelling lipid trafficking for the bacterial outer membrane (5R35GM128777-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9986822. Licensed CC0.

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