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.
Ciliopathies are a class of debilitating birth defects without known cures and limited but expensive treatments. Currently, we lack understanding of the underlying molecular network in ciliopathy patient cells and know even less about the causes of clinical presentations in ciliopathy patients. I propose to discover the differences in the molecular network between healthy cells and ciliopathy patient cells in an effort to better understand the molecular causes of clinical presentations possibly open new avenues for therapeutics.'''
| Verbeke, Eric J; Mallam, Anna L; Drew, Kevin et al. (2018) Classification of Single Particles from Human Cell Extract Reveals Distinct Structures. Cell Rep 24:259-268.e3 |
