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Molecular Genetics

Leading an effort toward comprehensive molecular analysis of cell type identity in the mouse brain and building state-of-the-art transgenic and viral tools to experimentally access cell types.   

Goals and Approach

Rotating mouse brain showing viral vectors
Serial two photon imaging following retroorbital injection of an enhancer-driven AAV vector expressing SYFP2. This vector was designed to target a specific glutamatergic cell population in central thalamus. This is one of the data modalities used in the Viral Genetic Tools Pipeline.

Mammalian nervous systems are composed of diverse neurons, some of which have been identified by one or more properties: specific shape, physiology, or molecular signature. However, a consensus approach to neuronal classification does not exist, and the correlations of different types of neuronal properties with one another and neuronal function have not been systematically examined. Therefore, scientists still don’t know how many different flavors of cellular building blocks comprise even relatively simple mammalian brains such as the mouse brain.  

The Molecular Genetics team at the Allen Institute for Brain Science approaches this question at the molecular level by analyzing transcriptomes and epigenetic landscapes of individual neurons. Through these efforts, they have discovered many specific marker genes and enhancers that can be used to classify these cells into types and that we use to create tools for genetic access to specific cell types. They also collaborate with many teams across the institute to establish multi-modal neuronal phenotyping and classification. In the long run, they hope their studies will reveal how molecular characteristics determine neuronal phenotypes, and how they govern myriads of functions carried out by mammalian brains.     

Projects

The Molecular Genetics team at the Allen Institute for Brain Science is measuring many properties at the single-cell level to define groups or cells that are similar to each other (for example, cell classes and types). They use single cell transcriptomics (scRNA-seq), single-cell epigenomics (snATAC-seq) and multimodal measurements to define cell types and marker genes and enhancers. They integrate the datasets computationally to produce integrative taxonomies of mouse brain cell types.

The Molecular Genetics team at the Allen Institute for Brain Science is using molecularly defined cell types to create various transgenic and viral tools to study cell types, their connectivity and their contributions to brain functions.

The Molecular Genetics team at the Allen Institute for Brain Science is using the tools they develop to define cell-type-specific connectivity in the mouse brain. They build and produce recombinant adeno associated viruses (AAVs) and rabies viruses for connectivity studies.

Science Programs at Allen Institute