- Meeting ID: 867 6409 6440
- passcode: 149120
13h00 - 13h30 – Madalena Chaves (Inria)
Two‑level modeling approach to identify the regulatory dynamics capturing drug response heterogeneity in single‑cells
Tumor cells of a clonal population exhibit multiple levels of heterogeneity, from gene expression to drug response. Cell-to-cell variability in cell death dynamics after treatment, is an emerging cause of drug resistance contributing to the reduced efficacies of cancer therapeutics (due to fractional killing). To study this problem, we developed a mass-action based apoptosis receptor reaction model and used single-cell response data to characterize its kinetic parameters. Analysis of the parameters distributions helped identify critical reaction steps that distinguish sensitive from resistant cells. Selected reaction sets were then augmented to incorporate a positive feedback loop involving caspase-8, a mechanism that enables the identification of fate-determining reactions and provides a robust basis for cell response heterogeneity.
This is joint work with Luis Gomes‑Pereira (Biocore, UCA) and Jérémie Roux (IRCAN, CRNS)
Dernière modification le 11/03/2022