The Norris Lab investigates the regulation of RNA processing by RNA binding proteins in the nervous system. Using the nematode C. elegans we can visualize RNA regulation in single neurons of living animals, and use the awesome power of genetics to investigate mechanisms and function. Here are some of the projects we are actively working on:


1) Regulation of RNA splicing in single neurons

We have adapted two-color fluorescent reporters that enable visualization of alternative splicing with single-neuron resolution in living animals. These reporters reveal lots of neuron-specific alternative splicing, and serve as entry-points to identifying regulatory mechanisms and potential function.


2) Genetic interactions among RNA binding proteins

We developed new CRISPR/Cas9 tools for the worm that allow us to mutate multiple genes in combinations. We have found that many RNA binding protein mutants have little or no phenotype on their own, but have strong phenotypes when combined with a second RNA binding protein mutation. These combinatorial genetics experiments shed light on otherwise hidden functions for RNA binding proteins.


3) Neuronal RNA binding protein combinations regulating lifespan

Our combinatorial CRISPR/Cas9 genetics approach has led to the surprising finding that multiple neuronal RNA binding protein combinations affect the lifespan of worms. We are now performing genetic and sequencing experiments to determine the cellular and molecular mechanisms by which they act.