Interdisciplinary Initiatives Program Round 13 - 2026
Project Investigators:
Marius Wernig, Pathology - Pathology Stem Cell Institute
Rongxin Fang, Neurosurgery
Abstract:
Population genetics has identified thousands of genetic variants linked to human diseases, but most of them fall outside the parts of genes that code for proteins, which makes their effects hard to understand. Many of these differences are located within the “untranslated regions” of messenger RNA - segments that help decide not only how much protein is made, but also where inside a cell that RNA is delivered. Location matters enormously in brain cells, which are long and highly compartmentalized: an RNA sent to a distant synapse lets a neuron respond and rewire locally, and misplaced RNAs are a feature of several neurological diseases. Yet how diseased associated genetic variants disrupt RNA subcellular localization remains largely unknown. This new collaboration between the Wernig and Fang laboratories will build the first imaging-based screen that can simultaneously read which genetic variant a cell carries and where its RNA travels inside human brain cells. By comparing healthy and disease-associated versions of ~1,000 variants across several human brain cell types, we aim to reveal a hidden layer of gene regulation and pinpoint causal variants that misroute RNA - opening new paths to understand, and ultimately treat, brain disease.
