# MATRIX PROTEINS IN METANEPHRIC DEVELOPMENT

> **NIH NIH K11** · UNIVERSITY OF WASHINGTON · 1994 · $87,297

## Abstract

This proposal describes a program utilizing didactic and
research experience for the development of an independent investigator in
the fields of extracellular matrix biochemistry, cell biology, and renal
development.  Phase I (years 1-2) of this proposal will consist of
graduate course work with a strong emphasis on biochemistry,
developmental cell biology, and advanced techniques in molecular biology.
Research projects during phase I will be supervised by an experienced and
recognized scientist in the field of extracellular matrix.  Mechanisms of
transcriptional regulation of the alpha1(I) collagen gene will be
identified in fetal calf ligament fibroblasts and in bovine aortic
endothelial cells exhibiting angiogenesis in vitro.  Cis-regulatory
regions will be identified by transfection with plasmids containing
fusion genes driven by alpha1(I) collagen 5' flanking and intronic
sequences and by DNA-protein binding analyses including mobility shift
assays and DNase I footprinting.  Phase I research will also include
development of expertise in techniques of murine metanephric explantation
and transfilter induction.  These culture systems will be used to analyze
the temporal-spatial expression of type I collagen, thrombospondin, and
SPARC (osteonectin) during induction and differentiation of the murine
metanephric mesenchyme.  This analysis will be performed by
immunohistochemistry, metabolic labeling and SDS-PAGE analysis of
secreted proteins, and Northern blot analysis of mRNA.  Specific cellular
levels of gene regulation will be identified.
          Phase II of this program will involve independent work by the
candidate in collaboration with the sponsor and will concentrate on the
mechanisms which regulate type I collagen expression after metanephric
induction.  Techniques, reagents, and results from Phase I will be used
to formulate an approach to transfection of transfilter-induced
mesenchyme.  The long term objectives of this work are to identify DNA
regulatory sequences and transcriptional factors which promote
metanephric differentiation.  These objectives are of direct relevance to
the understanding of abnormal renal development, the major cause of
kidney failure in childhood.

## Key facts

- **NIH application ID:** 2194405
- **Project number:** 5K11HD000939-04
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **SAM.gov UEI:** HD1WMN6945W6
- **Principal Investigator:** LAURIE S FOUSER
- **Activity code:** K11 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $87,297
- **Award type:** 5
- **Project period:** 1991-06-01 → 1996-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2194405

## Citation

> US National Institutes of Health, RePORTER application 2194405, MATRIX PROTEINS IN METANEPHRIC DEVELOPMENT (5K11HD000939-04). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2194405. Licensed CC0.

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