Project

Tools for mapping the molecular architecture and wiring of the brain

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Groups

Complex biological systems such as brain circuits are extended 3-D structures made out of nanoscale building blocks such as proteins, RNAs, and lipids, which are often organized with nanoscale precision. This presents a fundamental tension in biology - to understand a biological system like a brain circuit, you might need to map a large diversity of nanoscale building blocks, across an extended spatial expanse. We are developing a new suite of tools that enable the mapping of the location and identity of the molecular building blocks of complex biological systems such as the brain, aiming to map out the architecture of such systems with enough precision to understand how the structures of biological systems lead to function and dysfunction. One of the technologies we are developing, expansion microscopy (ExM), enables large 3-D objects to be imaged with nanoscale precision, by physically expanding preserved biological systems (in contrast to all previous microscopies, that magnify light from the sample via lenses). We are working to improve expansion microscopy further, and are working, often in interdisciplinary colla… View full description

Complex biological systems such as brain circuits are extended 3-D structures made out of nanoscale building blocks such as proteins, RNAs, and lipids, which are often organized with nanoscale precision. This presents a fundamental tension in biology - to understand a biological system like a brain circuit, you might need to map a large diversity of nanoscale building blocks, across an extended spatial expanse. We are developing a new suite of tools that enable the mapping of the location and identity of the molecular building blocks of complex biological systems such as the brain, aiming to map out the architecture of such systems with enough precision to understand how the structures of biological systems lead to function and dysfunction. One of the technologies we are developing, expansion microscopy (ExM), enables large 3-D objects to be imaged with nanoscale precision, by physically expanding preserved biological systems (in contrast to all previous microscopies, that magnify light from the sample via lenses). We are working to improve expansion microscopy further, and are working, often in interdisciplinary collaborations, on a suite of new labeling and analysis techniques that exploit the biochemical freedom enabled by the expanded state. We are also applying expansion microscopy to the scalable mapping of complex biological systems, including brain circuits. Such brain circuit maps may be detailed enough to enable detailed computer simulations of neural ciruits. Finally, we are extending and applying such tools to the early detection and understanding of complex diseases such as cancers and autoimmune diseases, and to the analysis of aging.

ExM resources

Learn more about Expansion Microscopy

ExM