Molecular Neuroscientist

We are hiring a PhD biomedical scientist with expertise in molecular biology. The lab studies molecular and circuit mechanisms of brain disease (Krishnan et al, Nature 2017) and human-specific retrotransposon-mediated gene regulation in neuronal circuit maturation and function as a basis of human brain evolution (Nadler et al. Commun. Biol. 2023). We perform in vivo mouse studies using constructed and packaged AAV virus (Cre- and Flp-conditional; stereotactic injected to specific brain regions in promoter-Cre/Flp mice; cDNA, shRNA, optogenetics, chemogenetics, retrograde circuit tracing, cell-type-targeted transcriptomics) and easy CRISPR genome engineering and bacterial artificial chromosome transgenics in mice (disease mutations, loxP/FRT flanking, IRES-Cre). For in vitro cell culture studies, we use human iPSCs (and other cell lines) differentiated (Ngn2 method) into mature neurons, modified using lentivirus (e.g., CRISPR deletion of gene regulatory elements). We perform CRISPR library screens and promoter-reporter luciferase assays. We are also adapting single cell/nucleus seq and spatial transcriptomics to analyze effects of interventions on gene expression and define behavior-regulating circuits relevant to human behavioral disease modeled in mice and to uncover molecular pathways in cell culture. We also investigate newly discovered T-cell immunologic disease mechanisms impacting circuits in human brain disease (e.g., obesity, autism, epilepsy, others). We have modeled these immune mechanisms in sporadic autism and obesity in mice. Finally, we are investigating human-specific retrotransposons SINE-VNTR-ALU (SVA) that we have shown regulate neurodevelopmental disease genes (e.g., CDK5RAP2, others) as a mechanism that may have promote specialized trajectories of brain development and function in human. We have a highly collaborative research team with tools developed by the molecular biologist studied in collaboration with experts in electrophysiologist and mouse behavior in the laboratory including the use of in vivo chemogenetic or optogenetic regulation of circuits during behavioral testing, in vivo mini-microscope implantation for regional cell-type specific monitoring of neuronal activity during behavior, and ex vivo acute brain slice whole-cell patch-clamp circuit analyses.