Missions

Within the framework of the ANR ABC4M project, the post-doctoral fellow will be in charge of the development of microscopy measurement methods of transcription regulation complex dynamics, as well as their analysis, and he/she will participate in the associated modelling work.

Activités

- Work on fluorescently labeled live cells
- Microscopy and measurement of molecular dynamics and interactions by FRET, FRAP, FCS, SPT
- Implementation of protocols and design of a multiplex measurement device
- Realization of experimental campaigns
- Data analysis and development of associated methods
- Contribution to the development of modeling methods
- Presentation of the results
- Publication of the results

Compétences

- Autonomy and organization in the work
- Work in a team
- Autonomy in microscopy
- Knowledge of basic cell biology

Contexte de travail

The post-doctoral fellow will work within the interdisciplinary team Dysco in the group of L.Heliot in the framework of the ANR project ABC4M in collaboration with the teams of Hugues Berry (INRAE, Lyon); Ignacio Izeddin (Inst. Langevin, Paris), Xavier Darzacq (Berkeley Univ, USA). This ABC4M project proposes to couple experiments and computer simulations to analyze the movement of P-TEFb components in living cells at several time scales. We will make measurements of the movement of P-TEFb in the nucleus of living cells at disjoint spatiotemporal scales (FCS and SPT) and interpolate these observations using an approximate Bayesian computation (ABC) approach with Monte Carlo simulations of P-TEFb diffusion as the statistical model used to fit the data. The parameters deduced from ABC will provide us with a multiscale quantification of the experimental data and help us resolve potential mismatches between different microscopy modes. We will also apply ABC-based model selection to determine the respective involvement of each microscopic mechanism (molecular crowding, binding, liquid phase condensates...) in the non-standard diffusion of P-TEFb. In order to provide a comprehensible picture of the orchestrated molecular dance that takes place in the nucleus during pause release, we will attempt to interpret experimental observations of P-TEFb dynamics under controlled or perturbed conditions (genetic mutants, RNA interference, pharmacological drugs).