High-Resolution Neurogenetics

Kraushar Lab

We study the most ancient macromolecular complex in the most evolutionarily recent brain region.

The brain is built during prenatal development by highly evolved gene expression programs. Our focus is the most evolutionarily recent brain region in mammals, the neocortex. We adapt 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 - among the most ancient macromolecular machines. Protein synthesis is particularly regulated in neurons, where the ribosome localizes, amplifies or suppresses, and precisely times protein expression. We perform measurements that target protein synthesis in action to track the precise location, birthdate, and lifetime of proteins in neurons.

We focus on how protein synthesis and turnover - “proteostasis” - establish a molecular logic of neuronal diversity in the neocortex.

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 microscopy.