Postdoc, Fred Hutchinson Cancer Research Center
The human brain contains more connections between neurons than the Milky Way has stars! The brain is wired at a gross level into stereotyped neural circuits that underlie sensation, information processing, motor output, and ultimately, consciousness. Disrupted neural circuitry is linked to many neurodevelopmental disorders, such as autism, epilepsy, and schizophrenia. How do the neurons of the brain connect and wire up into circuits? The goal of the research in the lab is to integrate genetics, biochemistry, cell biology, circuit function, and behavior, to understand how the brain creates functioning neural networks.
Neural circuits are defined by the connections made between neurons, and connections, termed synapses, come in two types: chemical, where transmission is mediated by neurotransmitters and receptors, and electrical, where neurons directly communicate with one another through gap junction channels. Our overarching goal is to decipher how the brain forms the correct types of neurons, with the right partners, at the right times in development - all ultimately ensuring proper circuit function and behavior.Image
Electrical synapses - We are interested in uncovering the mechanisms controlling electrical synaptogenesis. While the last decade has provided much insight into the mechanisms of building chemical synapses, electrical synapse formation is still poorly understood. However, it is known that electrical synapses are used by all animals both during development and in adulthood, where they are found in sensory, central, and motor circuits. The goal of this project is to unlock the molecular mechanisms underlying electrical synaptogenesis.
Synaptic coordination - Electrical synapses are well appreciated for forming early in development, followed by subsequent maturation into circuits containing both electrical and chemical synapses. We are interested in the coordination of these synapse types, and aim to uncover the principles that allow them interact. A major emerging goal of this project is to unlock the shared biochemistry found between both electrical and chemical synapses, as it represents a new frontier in neuroscience.
Molecular genetic tool engineering - As we investigate neural circuit wiring, we simultaneously focus on developing new tools for the field. We have developed methods for mapping mutations from forward genetic screens, we have pioneered CRISPR reverse genetic screening in zebrafish, and currently we are developing a single-cell RNA-seq atlas of zebrafish development.