# MOLECULAR BASIS OF PEROXISOMAL DISORDERS

> **NIH NIH K08** · JOHNS HOPKINS UNIVERSITY · 1994 · $80,730

## Abstract

The first three years of this award will be carded out under the direction
of Dr. David Valle in the Dept of Molecular Biology & Genetics at the Johns
Hopkins Univ School of Medicine.  His laboratory is extremely well-equipped
to provide me with a strong foundation in molecular biology and genetics,
which will add to my previous research experience and better enable me to
investigate human disease at the molecular level.  The last two years of
this award will assist me in starting my own laboratory within the Dept of
Pediatrics.  For this proposal, I will be investigating inborn errors of
peroxisomal biogenesis.  Peroxisomes are ubiquitous subcellular organelles
with a characteristic set of integral membrane proteins and over 40 matrix
enzymes which perform a variety of oxidative and synthetic reactions.
Several genetic diseases, including Zellweger Syndrome, neonatal
adrenoleukodystrophy, and infantile Refsum disease appear to be caused by
defects in the biogenesis of peroxisomes.  This laboratory is interested in
the molecular basis of these inborn errors.  Ongoing investigations in the
lab are aimed at Determining the normal function and possible involvement
of the 70 kD and 35 kD peroxisomal , membrane proteins in these disorders.
Human cDNAs for both these proteins have been isolated and characterized.
We are utilizing a large collection of cultured fibroblasts from clinically
and biochemically well-characterized patients with these disorders
(assembled by Dr. H.Moser). Erdman et al (1991) reported the isolation of a
S cerevisiae gene (PAS1) capable of rescuing mutants defective for
peroxisomal assembly.  PAS1 is not a membrane protein and it appears to
encode a previously-unidentified protein whose function is necessary for
peroxisomal biogenesis.  The overall aims of this proposal are to isolate
the human homolog of PAS1, determine if it has a similar function in
mammalian cells, and determine if mutations in this gene may be responsible
for one subset of defects in peroxisomal biogenesis.  The specific aims
are: to isolate a cDNA clone encoding human PAS1 either by use of
degenerate oligonucleotides or by functional complementation in yeast; to
determine the nucleotide sequence of the full-length human PAS1 CDNA and to
assess its ability to function in yeast; to delineate the organization of
the human PAS1 gene and determine its chromosomal localization; and to
identity and characterize mutations in the human PAS1 gene. in patients
with inborn errors of peroxisomal biogenesis.

## Key facts

- **NIH application ID:** 2194487
- **Project number:** 5K08HD000989-03
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **SAM.gov UEI:** FTMTDMBR29C7
- **Principal Investigator:** EMILY L GERMAIN-LEE
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $80,730
- **Award type:** 5
- **Project period:** 1992-08-01 → 1997-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2194487

## Citation

> US National Institutes of Health, RePORTER application 2194487, MOLECULAR BASIS OF PEROXISOMAL DISORDERS (5K08HD000989-03). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2194487. Licensed CC0.

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