Investigating the molecular mechanisms of peroxisomal membrane protein trafficking

Active Project Grant Awarded Last action

Award ID
F32GM161083
Recipient
Awarding agency
Obligated
$76,780

Award facts

Assistance listing
93.859 Biomedical Research and Research Training
Completion date 0% complete
Place of performance
Portland, OR 97239, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

Abstract
Peroxisomes are essential cellular organelles involved in lipid metabolism and cellular detoxification, yet the intricacies of their formation and maintenance remain poorly understood. Peroxisome biogenesis disorders (PBDS), including zellweger spectrum disorder (ZSD) and X-linked adrenoleukodystrophy, affect 1 in 50,000 births and cause devastating neurological and metabolic dysfunction due to defective organelle formation. A critical step in peroxisome biogenesis involves soluble and membrane protein import to immature peroxisomes. This research project aims to unravel the fundamental mechanisms of peroxisome biogenesis, with a focus on membrane protein trafficking to the peroxisomes. While soluble protein import to peroxisomes is well characterized, peroxisomal membrane protein (PMP) trafficking mechanisms remain poorly understood, representing a critical knowledge GAP that impedes our understanding and treatment of PBDS. To address this knowledge GAP, I propose to dissect the molecular details of PMP interaction with the peroxisome import receptor and chaperone- PEX19. Aim 1 investigates the biochemical and structural basis of human PMP- PEX19 complex formation. This aim will depict the molecular interactions between pmps and the import machinery to determine how post-translational modifications and protein-protein interactions govern organelle assembly. Aim 2 examines the disruptions of PEX19-dependent PMP trafficking in the context of genetic diseases, and upon drug treatment. I will use crispr-engineered, and ZSD patient-derived cell lines to gain holistic insights into trafficking disruptions in both disease and therapeutic contexts. The project will employ a multidisciplinary approach, combining cutting-edge structural biology techniques, biophysical assays, and advanced cellular imaging to investigate key protein interactions involved in peroxisome formation. Findings from this study will elucidate the underlying mechanisms of PMP import in peroxisomal biogenesis and open new doors to developing future therapeutic strategies for PBDS.

Quick answers

Who received award F32GM161083?

F32GM161083 was awarded to Oregon Health & Science University by National Institute of General Medical Sciences (National Institutes of Health) on March 1, 2027.

How much is award F32GM161083 worth?

$76,780 has been obligated on F32GM161083.

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