# Epithelial biology: morphogenesis and damage signaling

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA BERKELEY · 2024 · $853,020

## Abstract

PROJECT SUMMARY
Epithelia are the core cell type of animals, and constitute the most widespread and ancient mode of tissue
architecture. My lab uses a distinctive set of multidisciplinary strategies to study fundamental questions of
epithelial biology using Drosophila, leveraging deep evolutionary conservation to uncover general principles
applicable across phylogeny. The research proposed in this MIRA renewal tackles basic mechanisms underlying
epithelial organ shaping and the total body’s response to epithelial injury. Both goals -- one in which we have a
long track record and another stimulated by discoveries during the previous funding period-- build on my
laboratory’s 20-year NIGMS-funded research program.
In one direction we will investigate how developing epithelia respond not just to intracellular forces, but also to
resistance from the extracellular matrix. This understudied question is central to the morphogenetic movements
that allow organs to attain the specific forms required for function. Our previous work has shown how an organ
can be sculpted by finely patterned mechanical properties of the basement membrane that underlies all epithelia.
We will determine the mechanisms that regulate conserved matrix components and modifiers to achieve precise
mechanical patterning, and then exploit this knowledge to manipulate tissue shape in a predictable fashion.
In the other direction, we will explore the whole-body response to epithelial barrier damage. While the local
wound response is well-characterized and conserved across many phyla, animals also have systemic wound
responses mediated by signaling factors that communicate with distant organs. The mechanisms and impact of
these humoral responses, which include but are not limited to inflammation, are poorly understood compared to
the antimicrobial immune response triggered in parallel; they may include unappreciated signaling molecules
and exotic forms of signal transmission alongside well-known pathways such as TNF. Leveraging the strengths
of Drosophila for discovery biology, we will induce sterile injury in adult epithelial tissues and identify signaling
axes that communicate between the organ of insult and responding tissues to promote homeostasis and health.
This goal will include a comprehensive analysis of TNF signaling in the adult, and investigation of differences
between normal tissue repair and that triggered by chronic inflammation.
The proposed experiments tackle these key questions by combining the traditional strengths of Drosophila
genetics with advanced imaging and new biochemical techniques, empowered by collaborations. Our results
will enhance understanding of conserved mechanisms that generate functional epithelial organs during
development, and lay the foundation for addressing disorders driven by epithelial damage and pathology.

## Key facts

- **NIH application ID:** 10765564
- **Project number:** 2R35GM130388-06
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** David Bilder
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $853,020
- **Award type:** 2
- **Project period:** 2019-01-01 → 2029-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10765564

## Citation

> US National Institutes of Health, RePORTER application 10765564, Epithelial biology: morphogenesis and damage signaling (2R35GM130388-06). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10765564. Licensed CC0.

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