# Building and shaping narrow epithelial tubes in C. elegans

> **NIH NIH R35** · UNIVERSITY OF PENNSYLVANIA · 2022 · $657,567

## Abstract

Project Summary
My laboratory studies genes and cell biological mechanisms that form, shape and
protect epithelial tubes, with a focus on very narrow unicellular tubes and apical
extracellular matrix (aECM). Both are topics relevant to human diseases involving
capillaries and other narrow tubes, but are challenging to study in most animal models
due to difficulties in imaging the relevant structures and molecules. The nematode C.
elegans allows us to circumvent these challenges by permitting imaging of live animals
at sub-cellular resolution, combined with powerful genetic approaches to identify relevant
genes and pathways. Our recent work showed that a unicellular tube is shaped by: (i)
intracellular membrane trafficking events that rely on a fusogen protein (AFF-1) better
known for its roles in cell-cell fusion; and (ii) a newly discovered type of aECM that
precedes the cuticle and contains proteins similar to those found in or near some
mammalian ECMs (e.g. those with leucine-rich repeat, plasminogen, zona pellucida,
mucin and/or nidogen domains). This aECM also relies on putative lipid transporters of
the lipocalin, scavenger receptor B (SCARB) and Patched-related families. Our research
program in the next five years will follow up on these advances to better understand the
specific trafficking events involved in building unicellular tubes and the structure and
function of the aECM. For example, we will further test the model that AFF-1 mediates
endocytic scission to allow membrane to be shuttled from basal to apical surfaces to
extend the tube lumen, and we will identify AFF-1 domains and partners involved in this
scission function. We will investigate how specific glycoproteins traffic to and assemble
within the aECM, how proper aECM lipid content is regulated by transporter families,
and how individual aECM components affect the shape and integrity of differently-sized
tubes in the organism.

## Key facts

- **NIH application ID:** 10424426
- **Project number:** 5R35GM136315-03
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Meera Sundaram
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $657,567
- **Award type:** 5
- **Project period:** 2020-06-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10424426

## Citation

> US National Institutes of Health, RePORTER application 10424426, Building and shaping narrow epithelial tubes in C. elegans (5R35GM136315-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10424426. Licensed CC0.

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