Seminar of Nike Walther - Physics of Cells and Cancer Unit Institut Curie

Nike Walther  

 Transcription factors in action during cell state transitions – quantitative insights from live-cell single-molecule tracking in intestinal organoid models 

Abstract:  Transcription factors (TFs) mediate gene expression changes during embryonic development and adult differentiation. They thus represent one regulatory level crucial for the generation and maintenance of healthy tissues. However, it remains poorly understood how the biophysical properties and the dosage of TFs dynamically regulate cell state transitions. To address these questions in in vitro models of the rapidly renewing mammalian intestinal
epithelium, I established fast live-cell single-molecule tracking (SMT) and proximity-assisted photoactivation (PAPA)-SMT for dynamic protein interaction studies in multicellular intestinal organoids, and I developed an automated SMT imaging and analysis pipeline to resolve cellular subpopulations in heterogenous differentiation models. In this talk I will present how these technological advances allowed me to determine lineage TF-mediated regulatory principles of cell state transitions during intestinal differentiation and regenerative reprogramming based on context-dependent single-TF dynamics. I will further outline the power of the developed automated live-cell SMT framework to generate testable hypotheses towards unraveling molecular mechanisms underlying tissue-level phenotypes