We are interested in the way chromatin organizes inside the nucleus, and in particular the interaction that arises between different kinds of chromatin (euchromatin and heterochromatin) and the nuclear membrane along the different growth phases of budding yeast.
In recent investigations, we uncovered that heterochromatin forms aggregates that depend on a molecular glue (Sir3, Ruault et al., 2021) and localize at the nuclear membrane during exponential growth, while it localizes at the center of the nucleus in stationary phase (Guidi et al., 2015). We now want to study the determinants of nuclear localization, in presence and absence of known molecular tethers, and investigate the hypothesis that also the electrostatic potential generated by the nuclear membrane is a direct determinant of heterochromatin localization. Considering the fact that the quantity of DNA as well as the rate and quality of ion exchanges between the nucleus and the cytoplasm, including RNA and ATP, are dependent on metabolic activities.
In order to investigate this function, we propose an internship in Synthetic/Molecular biology to design, synthetise and test novel molecular tools. In particular, the intern will work on:
- a genetically encoded biosensor for membrane potential targeted to the nuclear inner molecular membrane.
- a genetically encoded light-sensitive protein that can alter the membrane potential, targeted at the inner nuclear membrane.
We search an enthusiast and curious intern, with molecular biology experience. All other skills required to accomplish the project, including gene editing CRISPR technology and confocal microscopy, will be taught by the supervisors. The work will be supervised by Alvaro Banderas (Synthetic Biology) and Vittore Scolari (Modelling and data analysis), at the Institut Curie. The intern will experience a dynamic interdisciplinary research context by being included in the activities of the laboratories of Angela Taddei and Pascal Hersen.
- Guidi M, Ruault M, Marbouty M, Loïodice I, Cournac A, Billaudeau C, et al. Spatial reorganization of telomeres in long-lived quiescent cells. Genome Biol 2015;16:206. https://doi.org/10.1186/s13059-015-0766-2
- Ruault M, Scolari VF, Lazar-Stefanita L, Hocher A, Loïodice I, Koszul R, et al. Sir3 mediates long-range chromosome interactions in budding yeast. Genome Res 2021;31:411–25. https://doi.org/10.1101/gr.267872.120