Discovery and characterization of novel ciliopathy protein complexes

NIH RePORTER · NIH · R00 · $244,394 · view on reporter.nih.gov ↗

Abstract

Abstract Ciliopathies are a collection of debilitating developmental disorders (e.g. Joubert syndrome, Meckel syndrome, Bardet-Biedl syndrome, orofaciodigital syndrome, polycystic kidney disease) which have no cures and limited but expensive treatments. Diagnosis and treatment is complicated due to ciliopathies causing multisystem pathologies and having large variance in their clinical presentations potentially resulting in neural tube defects, orofacial clefting, obesity, polycystic kidneys, retinal degeneration and in some cases, infant death. All ciliopathies are caused by dysfunctional cilia, the microtubule based organelle critical for cell-to-cell signaling, but currently there is limited understanding of the underlying molecular network responsible for proper cilia function. Recently, large-scale proteomic techniques have advanced where it is now possible to query the cell's molecular network and identify many new protein complexes. This proposal describes a research program that will 1) construct a ciliary complex map using proteomic techniques, 2) functionally characterize newly discovered ciliary complexes and 3) identify disruptions in complex assembly due to known ciliopathy mutations. Additional products of the proposed research will include a compendium of proteomic data on ciliated cells, statistical analysis tools for the discovery of protein complexes, functional characterization of critical ciliary processes and a more complete understanding of the underlying molecular network of ciliopathy disease states. This work aims to provide an important perspective of cilia biology in order to better understand the complex etiology and molecular causes of ciliopathies and potentially open new therapeutic avenues.

Key facts

NIH application ID
10438895
Project number
5R00HD092613-04
Recipient
UNIVERSITY OF ILLINOIS AT CHICAGO
Principal Investigator
Kevin Drew
Activity code
R00
Funding institute
NIH
Fiscal year
2022
Award amount
$244,394
Award type
5
Project period
2021-07-01 → 2024-06-30