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New Screen to Test Function of Neuronal microRNAs

Achievement/Results

IGERT fellow Matt Keuss has forged a new bridge between Professor Wirtz in Chemical and Biomolecular Engineering and Prof. Dawson in Neurology. They are now working on a screen to test the function of neuronal microRNAs. microRNAs are of tremendous interest in neuroscience because they a central to a newly discovered mechanism of gene regulation. Complimentary binding between microRNAs and messenger RNAs inhibits the translation of the messenger RNA. Hundreds of microRNAs are expressed in humans, a subset of which are specific to brain tissue. The screen will focus on microRNAs known to be present in the hippocampus and will test their function by overexpressing and inhibiting microRNAs in primary hippocampal neurons grown in culture. Effects on dendritic outgrowth, neuronal survival, dendritic spine morphology, and synaptic density will be assessed. microRNAs with robust effects will be selected for more detailed analysis. To quickly screen more than a few microRNAs the procedure for infecting, imaging, and analysis will need to be automated. Techniques for analysis are currently being developed using MetaMorph Imaging Software and custom algorithms written in Matlab. In the coming year, protein patterning techniques will be explored to assist in infecting neurons in an arrayed format to allow for automated microscopy.

Address Goals

Matt Keuss has created new collaborations by actively seeking out Prof T. Dawson of Neurology and Prof. Denis Wirtz of Chemical and Biomolecular Engineering. He convinced both professors that they could make new headway in neuroscience by combining their skill and approaches. Out-of-the-box approaches like Matt’s will lead to research outcomes that draw deeply on physic-chemical approaches and biological approaches leading to new synergies.

The research outcomes will advance NSF’s goals in fostering discovery based research