Fassberg Seminar: Discovering molecular nuts and bolts in the nervous system

We aim to discover molecular mechanisms that underpin neuron and circuit
properties. As entry points we identify /C. elegans/ mutants unable to adopt
particular behavioral states. Forward genetics is a potent tool to discover
biological mechanisms, but is limited by the laborious genetic mapping
associated with the approach. We show that bioinformatics alone can predict
phenotype-causing mutations in large collections of sequenced mutants. From >500
mutants defective in /C. elegans/group feeding behavior, we identify, thus far,
43 genes promoting this behavior. The proteins these genes encode define several
molecular machines. I will describe some of our discoveries. Unexpectedly, we
find that the pro-inflammatory cytokine interleukin 17 can act on neurons to
change circuit gain. We identify evolutionarily conserved complexes that act at
the endoplasmic reticulum to control biogenesis of ion channels and GPCRs. Using
biochemistry we are probing the functions of these complexes in mammalian cells.