# Analysis of Bulk Lipid Transport at Membrane Contact Sites

> **NIH NIH R01** · UNIVERSITY OF WISCONSIN-MADISON · 2024 · $497,317

## Abstract

ABSTRACT
All eukaryotic cells face the critical problem of regulating the subcellular distribution of lipids. The
lipid composition of organelle membranes is distinct, with each membrane containing a specific
subset of lipids that defines organelle identity and regulates organelle function. These membrane
lipids are also critical for intracellular signaling pathways and for proper control of lipid metabolism.
Not surprisingly, defects in the subcellular distribution or metabolism of these macromolecules
underlie many devastating human diseases. We recently identified and unified a novel family of
proteins: the bridge-like lipid transfer proteins (BLTPs). BLTPs are very large, rod-shaped proteins
with uninterrupted inner hydrophobic channels that serve as lipid superhighways between
apposing membranes at organelle contact sites. Although mutations in BLTPs are associated with
human disease, BLTPs are not required for single cell viability, a fact that has limited efforts to
understand how disruption of BLTP function contributes to disease. Our goal in this proposal is to
use an animal context to tackle this gap and, in doing so, uncover the biological significance of
BLTPs—and bulk lipid transport—to physiology and disease. We identified a Drosophila model
system where disruption of a single BLTP, BLTP2, results in dramatic physiological and cellular
phenotypes, leaving us uniquely poised to systematically dissect the molecular and cellular
functions of this protein and understand how BLTP dysfunction leads to disease. We will pursue
the following two specific aims: 1) Define the essential molecular properties of BLTP2. 2) How is
BLTP2 function at membrane contact sites regulated? Our long-term goal is to understand BLTP
function and how regulation of bulk lipid transport impacts animal physiology. We expect our
studies to reveal essential insights into the role of BLTPs in human disease which, in turn, we
hope will lead to novel therapies to treat disorders caused by BLTP dysfunction.

## Key facts

- **NIH application ID:** 10938815
- **Project number:** 1R01GM155154-01
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** ARASH BASHIRULLAH
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $497,317
- **Award type:** 1
- **Project period:** 2024-07-19 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10938815

## Citation

> US National Institutes of Health, RePORTER application 10938815, Analysis of Bulk Lipid Transport at Membrane Contact Sites (1R01GM155154-01). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10938815. Licensed CC0.

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