C. elegans High Throughput Compound Screen

Mohan Viswanathan, PhD

Massachusetts Institute of Technology (Boston, MA)

Dr. Viswanathan is a senior postdoctoral scientist in the laboratory of Dr. Leonard Guarente in the Department of Biology at MIT (Cambridge, MA).

Past Projects

Objective: 
Identify chemical suppressors of C. elegans fer-1

We are using the powerful invertebrate model organism Caenorhabditis elegans, a microscopic roundworm, as a platform for high-throughput compound screening to identify potential small molecule therapeutics for the treatment of Limb-Girdle Muscular Dystrophy 2B (LGMD2B) and Miyoshi Myopathy (MM). C. elegans FER-1 is the founding member of the ferlin family of transmembrane proteins and is homologous to human dysferlin, the protein mutated in LGMD2B/MM patients. C. elegans fer-1 mutants show defects in spermatocyte maturation, which profoundly affect sperm motility and egg fertilization. The biological basis of this block in spermatocyte development is a defect in regulated exocytosis; whereby intracellular vesicles, known as membranous organelles, fail to fuse properly to the plasma membrane of spermatocytes following a Ca2+- dependent activation signal. This cellular process is highly homologous to the membrane repair defect found in mammalian dysferlin mutants, namely an inability to fuse vesicles containing new membrane to existing plasma membrane in muscle cells. The major focus of our experimental strategy will be to identify chemical suppressors of the C. elegans fer-1 fertility defect. Compounds that restore fertility hold promise as leads toward therapeutic drugs for the treatment of LGMD2B and MM.