Mechanisms and regulation of chromosome segregation

A Crick PhD position for the 2021 programme in the lab of Frank Uhlmann. 

Project background and description

In the Chromosome Segregation Laboratory, we investigate molecular mechanisms that underpin faithful chromosome segregation during cell division. We use yeast as a model organism to study the contribution of structural chromosomal proteins to sister chromatid cohesion and chromosome condensation, essential processes that ensure faithful segregation of centimetre-long chromosomal DNA molecules within micrometre-sized cells. We also investigate how kinases and phosphatases of the cell cycle control network orchestrate the ordered progression through the successive stages of genome duplication and chromosome segregation. We have reached a stage where many of the key chromosome and cell cycle players have been identified and our focus turns to unravelling the fascinating mechanisms by which these molecular machines accomplish their tasks.[1-5]

Below are two reviews on the subject, as well as examples of publications from PhD students who recently graduated from our lab.

Candidate background

This project requires a strong interest in molecular mechanisms that underlie fundamental cellular processes. Techniques range from molecular genetics and genomics to protein biochemistry and proteomics.

References

1.       Uhlmann, F., Bouchoux, C. and López-Avilés, S. (2011)

          A quantitative model for cyclin-dependent kinase control of the cell cycle: revisited.

          Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences 366: 3572-3583. PubMed abstract

2.       Uhlmann, F. (2016)

          SMC complexes: from DNA to chromosomes.

          Nature Reviews Molecular Cell Biology 17: 399-412. PubMed abstract

3.       Thadani, R., Kamenz, J., Heeger, S., Muñoz, S. and Uhlmann, F. (2018)

          Cell-cycle regulation of dynamic chromosome association of the condensin complex.

          Cell Reports 23: 2308-2317. PubMed abstract

4.       Kataria, M., Mouilleron, S., Seo, M.-H., Corbi-Verge, C., Kim, P.M. and Uhlmann, F. (2018)

          A PxL motif promotes timely cell cycle substrate dephosphorylation by the Cdc14 phosphatase.

          Nature Structural & Molecular Biology 25: 1093-1102. PubMed abstract

5.       Liu, H.W., Bouchoux, C., Panarotto, M., Kakui, Y., Patel, H. and Uhlmann, F. (2020)

          Division of labor between PCNA loaders in DNA replication and sister chromatid cohesion establishment.

          Molecular Cell 78: 725-738.e724. PubMed abstract