The Conduit lab studies how microtubule nucleation is regulated in a cell-specific manner to allow different cells to form their specialised microtubule arrays.
Regulation of γ-TuRC activation
Microtubules are essential cell components linked to many human pathologies. They are nucleated
by muti-protein gamma-tubulin ring complexes (γ-TuRCs), which are themselves potential targets
for cancer therapy. Microtubule nucleation needs to be tightly controlled to allow cells to form their
complex microtubule networks. For this, γ-TuRCs remain inactive in the cytosol and are activated only
after recruitment to centrosomes during mitosis. This activation step appears to be mediated by the
binding of CM1 domain proteins, but the activation mechanism remains unknown. In Drosophila, the
CM1 domain protein Centrosomin (Cnn) binds and recruits γ-TuRCs to centrosomes during mitosis.
We recently showed that Cnn is auto-inhibited from binding γ-TuRCs in the cytosol, but that disrupting
this auto-inhibition resulted in ectopic microtubule nucleation throughout the cytosol and to cell division
defects (Tovey et al., 2021, JCB). The successful applicant will now explore how the binding of Cnn’s
CM1 domain activates γ-TuRCs. The project will involve purification of γ-TuRCs and Cnn fragments for
processing by Cryo-EM and analysis by single molecule microtubule nucleation assays.
This position is funded by an Agence Nationale de la Recherche (ANR) grant for 3 years in first instance.
Required to apply:
• PhD in cell biology
• A published first author paper (BioRxiv papers acceptable)
• Interest in microtubule biology
• Experience with protein purification
• Experience with TIRF microscopy
Applicants should send a CV, cover letter and contact information for two
referees to Paul Conduit (paul.conduit@ĳm.fr).
Informal enquiries about the project and job responsibilities are welcome
Details of our work can be found on the ĲM website: https://www.ijm.fr/research-topics/conduit-lab-va/?lang=en