UTSW-UNC Center for Cell Signaling Analysis

Ut Southwestern Medical Center, Dallas TX

Investigators

Linked publications & trials

Abstract

Cellular behavior is regulated by a varied signaling mechanisms, of which many depend on molecular dynamics precisely organized in space and time. The transient positioning and kinetics of molecular events is lost in bulk biochemical analysis and in single cell proteomics. Understanding such factors requires visualization and quantitative analysis of molecular events in living cells and tissues, now made possible by combining molecular probe design, high-resolution live cell microscopy development and computational image analysis. Quantitative analysis of live cell signaling networks has been accessible only to specialized teams who unite these capabilities. The Center for Cell Signaling Analysis enters Year 4 building upon substantial progress made in Years 1–3, continuing efforts to democratize advanced methods and put these tools in the hands of scientists who have not devoted their careers to imaging. We will continue to develop and disseminate a user-friendly and integrated pipeline that combines 1) biosensors, optogenetics and chemogenetics 2) modular, high-speed, and high-resolution light-sheet microscopes, and 3) image analysis and computational modeling to derive signaling network architecture, including the causality and kinetics of connections. The Technology Development Projects (TDPs) in Year 4 will build upon these established foundations and focus on further advancing: i) Open-source software for the analysis of subcellular signal transduction in 2D and 3D live cell time-lapse data using advanced methods in statistical time series analysis. ii) Optogenetics, chemogenetics, and biosensors based on alternate approaches with complementary capabilities and reduced perturbation of signaling. iii) Multiple modular, cost-effective, and high-resolution 3D light-sheet microscopes that can be assembled rapidly by non-experts and deliver ~220 and ~450 nm lateral and axial resolution. Through our collaborative Driving Biological Projects (DBPs), we will extend earlier efforts to iteratively refine and improve our image analysis methods, probes, and imaging platforms. We also propose a strong dissemination component that continues and expands activities from the first three years, maximally leveraging existing infrastructure, including imaging facilities, Addgene, GitHub, and Applied Scientific Instrumentation. We will continue to provide extensive training (in person, remote, topic-driven courses, and YouTube tutorials) and centrally organize Center outputs on a comprehensive and continuously updated website.