Nathalie Delgehyr
The centrosome is composed of two centrioles and associated pericentriolar material (PCM). In most cells, the centrosome acts as the principal microtubule-organizing centre. Its biogenesis is tightly controlled during the cell cycle to duplicate only one centrosome per cell. However, the different mechanisms governing centrosome biogenesis are poorly understood.
The capacity of the centrosome to nucleate microtubules varies during the cell cycle with an important increase of this capacity at mitosis onset, a process called centrosome maturation. It has been shown that polo is a key regulator of centrosome maturation but the targeted proteins are unknown. In absence of active polo, proteins involved in microtubule nucleation, like the gamma-TuRC, are not anymore recruited at the spindle pole.
I have designed an assay, using RNAi to deplete candidate proteins in cultured cells, to decipher which proteins are involved in centrosome maturation. I am analysing the phosphorylation of those proteins by polo in vivo (in presence or absence of active Polo) and in vitro.
Finally, I am also interested in understanding how tubulin biogenesis is controlled.
A mutant called merry-go-round (mgr) was isolated from an EMS screen. We have found that its gene encodes a homologue of a component of the Gim (Genes Involved in Microtubule biogenesis) co-chaperone complex. Low levels of alpha- and beta-tubulin are detected in mgr mutant flies, with a more marked effect in testis than neuroblasts. This tubulin decrease is associated with an increase of monopolar spindles in neuroblasts and defective meiosis in testes. In order to understand the mechanisms underlying tubulin degradation, we analysed mgr RNAi depleted cells. Downregulation of MGR leads to a decrease of beta-tubulin levels, formation of monopolar spindles and abnormal centrioles. This centrosome duplication failure is a slow process that builds-up with time, suggesting that it might be a consequence of tubulin degradation. Accordingly cells treated by RNAi to partially deplete beta-tubulin showed similar phenotypes.
Areas of interest:- Centriole biogenesis
- Centrosome maturation
- GimC
- Polo
Nathalie Delgehyr
Address:
Department of Genetics,
University of Cambridge,
Downing Street,
Cambridge,
CB2 3EH,
England.
Email:
nd276@cam.ac.uk
Back to the list of current members.
Information about former members of the Glover group is available.