“Profiling molecular, structural, and functional features within intact biological systems”
Holistic understanding of complex biological systems, from single biomolecules to cell interactions across whole organs, will require integrated methodologies that can simultaneously probe both nucleotides and proteins in intact tissue. While several fixation strategies have been explored to preserve individual molecular features (e.g. fluorescent activity of protein reporters, mRNA transcripts, or protein antigenicity), a universal volumetric imaging method to profile all biomolecule types remains to be developed. In this talk, I will describe how multifunctional cross-linkers with tightly regulated reaction kinetics can form cohesive tissue gels by binding together biomolecules of interest. I will show how these flexible and multifunctional linkers protect proteins and nucleotides from deteriorating in harsh chemical conditions by forming both intra- and intermolecular bonds. By applying our method to various tissue types, I will describe potential applications for phenotyping of neural circuits.
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