# Development of novel genetic tools for the study of type IV collagens

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2024 · $246,000

## Abstract

PROJECT SUMMARY
The broad goal of our research is to understand the biological functions of type IV collagens in the extracellular
matrix and determine the mechanisms by which they cause genetic and acquired diseases. Type IV collagen
alpha 3 (COL4A3), COL4A4, and COL4A5 form a heterotrimer that is critical to the function of the glomerular
basement membrane. It has been known for decades that COL4A3, COL4A4, and COL4A5 mutations cause
inherited nephropathies, however, collagens are stable, insoluble proteins that are difficult to isolate which has
been a significant barrier to their study. The purpose of this proposal is to validate a novel and powerful tool that
enables unveiling of spatiotemporal changes in collagen deposition and degradation and enhance the ability to
isolate collagens for biochemical characterization in physiological and pathological contexts.
The inability to distinguish cell type specific or temporal changes to the extracellular matrix constitutes a
significant obstacle for understanding a fundamental aspect of tissue biology. To address this barrier, we will
develop two mouse lines in which type IV collagens are fused with switchable fluorescent proteins for isoform-
specific visualization and biochemical tags for differential affinity purification. These simple but powerful tools will
enable unprecedented characterization of spatial, temporal, biochemical and biophysical parameters of ECM
that are currently impossible to achieve. If the detailed validations outlined in this proposal are successful, we
will have developed a transformative tool that will provide significant insight into a fundamental aspect of tissue
biology and that can be applied to every organ of the body in normal development or in pathological settings.

## Key facts

- **NIH application ID:** 10975838
- **Project number:** 1R21DK140866-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Douglas Gould
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $246,000
- **Award type:** 1
- **Project period:** 2024-08-19 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10975838

## Citation

> US National Institutes of Health, RePORTER application 10975838, Development of novel genetic tools for the study of type IV collagens (1R21DK140866-01). Retrieved via AI Analytics 2026-06-15 from https://api.ai-analytics.org/grant/nih/10975838. Licensed CC0.

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