Anatomical precision of inter-neuronal connections is essential for the normal development and function of our brain. These connections are established through the extensions of subcellular cable-like structures, called axons that form synaptic connections with the dendrites of their target neurons. This process involves sequential events, from sending out axonal cables to the correct target, to docking of the cable terminal at the appropriate synaptic site on its target dendrite. The transition of these events requires precise timing mechanisms, but the timing devises used by neurons for making precise connections are only partly understood. This research focuses on studying this question in an experimental animal, called Caenorhabditis elegans, using a combined genetic, molecular, and optic approach. C. elegans, a soil worm, is a well-established experimental system for which its neuronal map is completely known. A recent surprising discovery revealed existence of a timing device involving microRNAs used in neurons to time when their connections actually form during development of the C. elegans brain. The goal of this project is to understand how this neuronal timer controls the precisely timed events required for making specific connections between neurons. Genes that allow neurons to connect with each other to form functional units are highly similar between worms and humans. Thus, what the outcomes of this work in worms will likely be relevant to understanding the human brain.
All proposed experiments will be carried out by postdoctoral fellows, graduate and undergraduate students. This research will be an important component of their training for careers in scientific disciplines. The PI's lab is currently one of the only two labs in the greater Cincinnati area using C. elegans as an experimental platform for discovery and thus is well-positioned to introduce research on this model organism to students at many levels. The PI makes strong efforts to recruit members of underrepresented groups and has demonstrated a strong track record to disseminate scientific knowledge to broad audiences. Thus, the proposed project integrates scientific discovery with broad promotion of teaching, learning and training.
