High-Resolution Neurogenetics

Kraushar Lab

Our mission is to tackle multidisciplinary scientific challenges as a diverse team.

We study the most evolutionarily ancient macromolecule in the most evolutionarily advanced brain region.

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 focus is the most evolutionarily advanced brain region in mammals, the neocortex. 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. Protein synthesis is particularly regulated in neurons. Neurons are especially long-lived, with a uniquely wide range of protein lifetimes. Neuronal morphology is especially complex, where local translation sculpts synapses in remote dendritic compartments. Measurements that target protein synthesis in action can pinpoint the precise birthdate and location of gene expression in neurons.

The specific focus of our laboratory is how protein synthesis and turnover - “proteostasis” - establishes 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.