We seek to understand how are the properties of an organism – its development, physiology and behavior – are encoded in its genome. We primarily use molecular genetics of the nematode Caenorhabditis elegans but also apply proteomics, computational biology, biochemistry, cell biology, imaging, behavioral analysis, optogenetics, synthetic biology to not only C. elegans but also parasitic nematodes, budding yeast, mice, jellyfish, fungi, and human cells as needed.
Specific areas of current interest are:
How does the 302-neuron worm brain assess the future environment based on computation of sensory and physiological inputs?
Does the male worm have a neural representation of its mating partner?
How can we best predict gene expression from DNA sequence?
What are the functional consequences of de novo genetic variants found in individual with autism spectrum disorder?
What changes in the nervous system occur during sleep?
How do cells migrate accurately during development?
Our major strategy is to perturb the activity of one or more genes and measure how cells or animals misbehave to infer gene function and genetic pathways. We measure gene expression by RNA-seq and transgenic reporters; we measure behavior using automated systems and optogenetics. We focus on intercellular signals and their transduction by the responding cell into transcriptional outputs. Many of the genes we have identified are the nematode counterparts of human genes, and we are leveraging C. elegans molecular genetics to study human genes with no actionable information and of the consequence of variants found in human individuals, including those with autism spectrum disorder. Nematodes are major health and agricultural problems, so we focus on parasite relevant biology such as dauer/infective juvenile development, using genomics and molecular genetics.