BBSRC funding success for Dr Vakonakis' work on centriole assembly

Wellcome Trust research fellow Dr John Vakonakis together with co-investigator Dr Michèle Erat have been awarded a BBSRC project grant for their work on centriole assembly.

Dr Vakonakis and his team are part of a successful international collaboration who were among the first to show that the basis of centriolar nine-fold symmetry lies in a single protein called SAS-61, (see news: ‘Single protein holds key to building up cell structures’).

The new funding of a grant of over £500,000 for ‘Structural mechanisms of centriole assembly during cell duplication’ will greatly strengthen their research in this highly competitive field.

Cartoon representation of the cartwheel model structure of the centriole of algae Chlamydomonas reinhardtii. Nine SAS-6 dimers interact to form a closed ring structure. This model was derived from crystal structures and validated by electron microscopy data

Cartoon representation of the cartwheel model structure of the centriole of algae Chlamydomonas reinhardtii. Nine SAS-6 dimers interact to form a closed ring structure. This model was derived from crystal structures and validated by electron microscopy data (Click to enlarge)

As Dr Vakonakis explains, centrioles form the basis of the centrosome which organises the microtubules that build up the mitotic spindle. It is essential that proper centriole duplication takes place once per cell cycle to ensure genome stability. Errors in the duplication process are linked to cancer and a number of other diseases.

Despite their importance, detailed insight into the assembly of these large molecular machines is still lacking. Although the first microscopic images of centrosomes stem from more than one hundred years ago, we are only now beginning to elucidate the details of their structural components.

This BBSRC grant will support structural studies using high-resolution techniques such as X-ray crystallography and NMR to look at the centriolar components and their interplay in detail. Mechanistic insights from Dr Vakonakis’ research can immediately be tested in vivo by collaborating laboratories at École Polytechnique Fédérale de Lausanne in Switzerland.

‘It is very rewarding to see one's efforts at the molecular level being directly translated into the relevant biological organism,’ says co-investigator Michèle Erat. ‘In this project, many people from different countries and with very different expertise work together to understand this highly complex biological system. And at the heart of it lie our structures. This is really exciting research.’

The ultimate goal of this project is the creation of a blueprint of centriole assembly, including details of the various protein interfaces and the regulatory mechanisms involved. These results could help in the development of new therapeutic agents against a variety of disease conditions, including male sterility and cancer.

Reference

  1. Structural Basis of the 9-Fold Symmetry of Centrioles. Kitagawa, D., Vakonakis, I. et al. Cell doi:10.1016/j.cell.2011.01.008





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