Modeling molecular and cellular aspects of human disease using the nematode Caenorhabditis elegans.
As an experimental system, Caenorhabditis elegans offers a unique opportunity to interrogate in vivo the genetic and molecular functions of human disease-related genes. For example, C. elegans has provided crucial insights into fundamental biologic processes, such as cell death and cell fate determinations, as well as pathologic processes such as neurodegeneration and microbial susceptibility. The C. elegans model has several distinct advantages, including a completely sequenced genome that shares extensive homology with that of mammals, ease of cultivation and storage, a relatively short lifespan and techniques for generating null and transgenic animals. However, the ability to conduct unbiased forward and reverse genetic screens in C. elegans remains one of the most powerful experimental paradigms for discovering the biochemical pathways underlying human disease phenotypes. The identification of these pathways leads to a better understanding of the molecular interactions that perturb cellular physiology, and forms the foundation for designing mechanism-based therapies. To this end, the ability to process large numbers of isogenic animals through automated work stations suggests that C. elegans, manifesting different aspects of human disease phenotypes, will become the platform of choice for in vivo drug discovery and target validation using high-throughput/content screening technologies.
Department of Pediatrics, Children's Hospital of Pittsburgh and Magee-Womens Hospital Research Institute, Department of Cell Biology and Physiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA. gsilverman@upmc.edu
Gary A
GA
Silverman
Cliff J
CJ
Luke
Sangeeta R
SR
Bhatia
Olivia S
OS
Long
Anne C
AC
Vetica
David H
DH
Perlmutter
Stephen C
SC
Pak
D000818:Animals; D030801:Animals, Genetically Modified; D017209:Apoptosis / Q000235:genetics; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D017124:Conserved Sequence; D018509:DNA, Helminth; D030541:Databases, Genetic; D055808:Drug Discovery; D005786:Gene Expression Regulation / Q000187:drug effects; D020022:Genetic Predisposition to Disease; D054884:Host-Pathogen Interactions / Q000235:genetics; D006801:Humans; D023421:Models, Animal; D009154:Mutation; D009336:Necrosis; D010272:Parasitic Diseases / Q000235:genetics; D010641:Phenotype; D015203:Reproducibility of Results; D013045:Species Specificity
D018509:DNA, Helminth