This $2.8 million project grant from the National Institutes of Health Office of the Director, under the Trans-NIH Research Support program (CFDA 93.310), will fund the development of multifunctional phase sensors to probe and manipulate intracellular biomolecular condensates in brain organoid models. Emory University, as the primary awardee, will engineer sensors encoded with ultra-weak multivalent interactions and fluorescent and catalytic domains to serve as multi-functional liquid-liquid phase separation probes. Georgia Tech Research Corporation will also receive subaward funding to support this work. By catalyzing biotinylation and protein disaggregation, the next-generation sensors will enable biomolecular dissection of intrinsically disordered protein assemblies and provide tools for combating neuropathological aggregates linked to neurodegenerative diseases like Alzheimer's, frontotemporal dementia, and ALS. This innovative sensor platform aims to advance understanding of pathological protein condensates through live cell imaging and proximity proteomics in brain organoids, with the goal of generating insights into age-dependent human neurodegeneration.
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