Harvard Postdoctoral Fellowship in Molecular and Circuit Studies of Autism
The Anderson Laboratory is located in the new Center for Life Sciences (CLS, 3 Blackfan Circle, Boston, MA). This building houses the major neuroscience and biomedical research laboratories of Beth Israel Deaconess Medical Center, Children’s Hospital Boston, Harvard Wyss Institute for Biologically Inspired Engineering, and Dana Farber Cancer Institute. Dr. Anderson is a member of the Children's Hospital Boston Intellectual Disabilities and Developmental Diseases Research Center (http://www.iddrc.org/childrens-hospital-boston/index.php/investigators/). Other major laboratories in CLS include Clif Saper, MD, PhD; Brad Lowell, MD, PhD; Chris Walsh, MD, PhD; Clifford Wolfe, PhD; and Mustafa Sahin, MD, PhD. The Anderson Laboratory occupies 1,500 square feet, and contains all laboratory equipments and reagents necessary for molecular biology (Cre/loxP conditional and AAV steriotactic gene deletions and expression, chemogenetics, optogenetics, Cas9 genome editing, RNA transcript profiling), in vitro brain slice patch clamp electrophysiology including optogenetics, in vivo electrophysiological, freely moving in vivo cell-type specific neuron population calcium imaging with Inscopix, and mouse behavioral analyses.
We seek individuals with expertise in molecular biology/Cas9 genome editing/viral vectors and others with expertise in computational analysis of behavior using video image analysis, steriotaxic brain injections, and implanted in vivo mini-microscope imaging of calcium in specific neurons (AAV-DIO-GCaMP, promoter-Cre). The methods will be complemented by the following experimental approaches ongoing in the laboratory: 1) further engineering and packaging of our existing set of Cre-conditional AAV viral constructs (optogenetic, chemogenetic, activity tagging, calcium imaging, shRNA, Cas9/gRNA); 2) generation of new mouse lines using Cas9/gRNA/targeting construct trangenics; and 3) RNA sequence analysis (fluorescence guided flow purification for population and single cell transcriptomics). Others in the laboratory provide collaborative support for projects including bioinformatics analysis of transcripts and optogenetic slice patch clamp electrophysiology. The laboratory focuses on mapping the neuronal circuits underlying component behavioral deficits in autism (e.g., sociability, social vocalization, aggression, intellectual disability) (see Krishnan et al. Nature 2017). We utilize the rich autism genetics data sets and the above technologies to uncover autism gene molecular pathways that disrupt these circuits to produce component behavioral deficits.
In parallel, the laboratory is also characterizing the human autism postmortem using various molecular and quantitative imaging approaches. By using the pathologic findings as a framework for the human autism genetics data sets (copy number variations and exome sequencing mutations), we are guided to generate specific conditional genetic mouse models for specific autism genes with the goal of reconstituting these pathologies and understanding the molecular pathways involved.
Experience with at least a subset of the listed technologies. PhD in neuroscience or other fields with a strong emphasis on molecular biology.
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