Widefield Fluorescence Microscope for Ultra-Long-Term Time-Lapse Imaging

• Subject Area: Basic Research in Biology and Medicine
• Term: Funded in 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 544665512

The Junior Research Group “Signaling Dynamics of Cellular Biomedical Systems” at the Institute of Cell Biology and Immunology aims at dissecting the molecular origins of cell-to-cell heterogeneity and its implications for human diseases. Cancer is a leading cause of death. Despite the development of increasingly effective targeted therapies, cancer proliferation is often not fully repressed, with tumors typically relapsing within months of treatment. One critical route is acquired resistance, in which drug-sensitive cells initially adapt to the drug action via non-genetic mechanisms and subsequently accumulate genetic mutations enabling permanent resistance during drug exposure. Despite its clear medical relevance, our knowledge remains limited at the cellular scale and resolution, due to the lack of techniques that simultaneously capture the cell-to-cell heterogeneity and the signaling dynamics over long periods. In his postdoctoral research, the applicant has overcome this barrier with an innovative pipeline of time-lapse microscopy and automated cell tracking, by which thousands of single drug-treated cancer cells can be monitored continuously for up to two weeks. As a Junior Professor, he will combine this pipeline with classical biochemical and genetic approaches to perform an in-depth characterization of cancer-cell fates across the entire timeline of acquired resistance at the single-cell resolution, uncovering the dynamics and the sequences of events by which drug resistance emerges. For this reason, a widefield fluorescence microscope capable of ultra-long-term time-lapse experiments (minimum 7 days) is sought as the central equipment for his research group. The microscope will be operated in the Technology Platform “Cellular Analytics” of the Stuttgart Research Center Systems Biology and will thus be open to all the members and the associated working groups across the university. The time of usage in the first year is calculated as 4,200 hours by the Junior Research Group and 5,500 hours overall.

• DFG Programme: Major Research Instrumentation
• Major Instrumentation: Weitfeld-Fluoreszenzmikroskop für Langzeit-Observation lebender Zellen
• Instrumentation Group: 5000 Labormikroskope
• Applicant Institution: Universität Stuttgart
• Leader: Professor Dr. Chengzhe Tian