Funded for 3 years
Supervision by Anna Polesskaya (CNRS Staff Researcher)
and Alexis Gautreau (CNRS Research Director)
Tight collaboration with the group of Gregory Giannone (University of Bordeaux)
Main Goal
Cell migration is powered at the leading edge by branched actin generated by the WAVE and Arp2/3 complexes. Recent biochemical analyses have revealed a diverse arrays of related complexes, whose role in cell migration is not yet fully deciphered. Recent proteomics screens have revealed novel partners of both types of complexes that appear to play a role in the persistence of cell migration. The PhD student will generate knock-out and knock-in cell lines to analyze in detail phenotypes associated with gene inactivation and dynamics of the encoded proteins. Protein behavior will be analyzed at the nanoscale in collaboration with Giannone’s group.
Technologies
Generation of knock-out and knock-in cell lines by CRISPR-Cas9
Videomicroscopy & super-resolution microscopy
Quantitative analyses of cell behavior and protein dynamics
References
Visweshwaran SP, Thomason PA, Guerois R, Vacher S, Denisov EV, Tashireva LA, Lomakina ME, Lazennec-Schurdevin C, Lakisic G, Lilla S, Molinie N, Henriot V, Mechulam Y, Alexandrova AY, Cherdyntseva NV, Bièche I, Schmitt E, Insall RH, Gautreau A. 2018. The trimeric coiled-coil HSBP1 protein promotes WASH complex assembly at centrosomes. EMBO J. 37:e97706.
Molinie N, Rubtsova SN, Visweshwaran SP, Rocques N, Polesskaya A, Schnitzler A, Vacher S, Denisov EV, Tashireva LA, Perelmuter VM, Cherdyntseva NV, Bièche I, Gautreau AM. 2019. Cortical branched actin determines cell cycle progression. Cell Res 29:432-45.
Fokin AI*, David V*, Oguievetskaia K, Derivery E, Stone C, Cao L, Rocques N, Molinie N, Henriot V, Aumont-Nicaise M, Hinckelmann MV, Saudou F, Le Clainche C, Carter AP, Romet-Lemonne G, Gautreau AM. 2021. The Arp1/11 Minifilament of Dynactin primes the Endosomal Arp2/3 Complex. Sci Adv. 7:1-11, eabd5956.
Mehidi A, Kage F, Karatas Z, Cercy M, Schaks M, Polesskaya A, Sainlos M, Gautreau AM, Rossier O, Rottner K and Giannone G. 2021. Forces generated by lamellipodial actin filament elongation regulate the WAVE complex during cell migration. Nat Cell Biol. 23:1148-62
Gautreau AM, Fregoso FE, Simanov G, Dominguez R. 2022. Nucleation, Stabilization and Disassembly of Branched Actin Networks. Trends Cell Biol. 32:421-432
Recent relevant manuscripts can be found on BioRxiv
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