C. elegans as a model system for human disorders

C. elegans as a model system for human disorders 

Identification of neuronal signaling as a modulator of protein homeostasis in C. elegans muscle cells

Abstract

Caenorhabditis elegans and mammals share a high conservation of molecular and cellular pathways, with the majority of human disease genes and pathways present in the worm. This conservation and the availability of molecular tools and techniques for this organism make it both an ideal model for the identification of conserved genes relevant to human disease as well as whole-genome approaches to the study of conserved cellular pathways.

One example of a highly conserved cellular pathway is the molecular response  to misfolded proteins, which is generally studied as a cell-autonomous process. We used C. elegans as a model system to identify and characterize  modulators of protein folding/misfolding pathways. Our studies revealed that neuronal signaling is an important modulator of protein homeostasis in  post-synaptic muscle cells. We genetically established that defective gamma-aminobutyric acid (GABA) signaling or increased acetylcholine (ACh) signaling causes a general imbalance in protein homeostasis in post-synaptic muscle cells. These results demonstrated the importance of intercellular communication in intracellular homeostasis.
Similar molecular approaches, using C. elegans as a model organism, are now being taken in the study of specific RNA transcripts known to act as pathogenic entities in the cell.

Speaker: Susana M. D. A. Garcia

Affiliation: Department of Molecular Biology, Massachusetts General Hospital, Boston, USA
                  Department of Genetics, Harvard Medical School, Boston, USA

Host: Pedro Domingos