High-Resolution Neurogenetics

High-Resolution Neurogenetics

Kraushar Lab - OWL Group

 

Our research focuses on the most evolutionarily advanced brain regions that generate our complex thoughts and behaviors. Defining the brain’s gene expression program has been a central challenge for neuroscience, and key to understanding how the brain evolved its unique structure and function. We study the brain as it is being built, during prenatal development when stem cells differentiate into distinct neurons to create different circuits. Our work adapts cutting-edge technologies to analysis of this complex developmental system, with the goal of visualizing gene expression in action at high-resolution.

The final critical gatekeeper of gene expression is mRNA translation into protein by the ribosome. Protein synthesis is a unique step of gene expression because it can be sub-cellularly targeted, and can amplify or suppress protein output by orders of magnitude. Ribosome localization in neuronal compartments, including dendrites, axons, and synapses can respond to neuronal signaling. Measurements that target protein synthesis in action can pinpoint the precise location and birthdate of gene expression.

Bridging the gap from the transcriptome to the targeted and timed proteome of neurodevelopment is at the leading edge of defining the brain’s developmental gene expression program. The focus of our laboratory is how spatially targeted and precisely timed protein synthesis generates a dynamic gene expression program during neurodevelopment.

Our approach is highly multidisciplinary for analysis at all scales – from tissue patterning of neuronal circuits down to atomic resolution. Our tools include analyses like Ribosome Profiling, pSILAC Mass Spec, Click Chemistry, and high-resolution imaging – including cryo-electron microcopy.

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