What if, instead of trying to zoom in on the nanoscale structures of the brain, we made them bigger?
Dr. Edward Boyden and his team at MIT are doing just that. The process, known as expansion microscopy (ExM), physically enlarges brain tissue so that even extremely small molecular structures are viewable on a conventional light microscope.
In his 2016 TED Talk, Dr. Boyden says: “Can we make [the brain] bigger? Big enough that you can peer inside and see all the tiny building blocks, the biomolecules, how they’re organized in three dimensions, the structure…. if we could get that, maybe we could have a better understanding of how the brain is organized to yield thoughts and emotions and actions and sensations. Maybe we could pinpoint the exact changes in the brain that result in diseases like Alzheimer’s, epilepsy, and Parkinson’s.”
Thanks to a grant from the National Institute of Mental Health (NIMH), MBF Bioscience, is teaming together with Dr. Boyden’s group to develop high performance, advanced software to analyze tissue processed by expansion microscopy. The new software will be able to perform comprehensive spatial distribution analysis of molecular structures, such as populations of messenger RNAs and proteins.
“The goal is to be able to pinpoint the exact molecular changes that occur in brain disorders in order to identify new therapeutic targets,” says MBF Bioscience President Jack Glaser.
The groundbreaking technological advantage of ExM is the ability to isotropically expand tissue and increase the size of biological structures. This allows nanoscale-resolution, light-microscopic imaging of objects that are too small to be observed without expansion due to the diffraction limit of light.
Among other benefits, ExM allows small structures to be imaged with a wider range of microscopy techniques. Processing tissue for ExM also allows repeated hybridization (for investigations of mRNAs) and/or repeated antibody staining (for investigations of proteins) of the same tissue, combined with repeated microscopic imaging rounds.
An important innovation in our new system is to empower biologists by giving them the ability to perform all of these tasks without the need to have a computer scientist on staff to run software scripts developed for each step of this kind of complex analysis.
ExM and our new software will enable substantial advancements in research studies focusing on alterations in the spatial transcriptome and proteome of neurons associated with neurodevelopmental, neuropsychiatric, neurodegenerative, and neurological disorders as well as in aging research and drug development.