Biochemistry & Proteomics Cell Biology Cell Cycle & Chromosomes Genetics & Genomics Genome Integrity & Repair Model Organisms Structural Biology & Biophysics
A 2023 Crick PhD project with 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.
Below are two reviews from our lab on these subjects, as well as three examples of research publications from PhD students who recently graduated.
This project requires a strong interest in molecular mechanisms that underpin fundamental cellular processes. Techniques range from molecular genetics, genomics and proteomics to protein biochemistry and biophysics.
1. Uhlmann, F. (2016)
SMC complexes: from DNA to chromosomes.
Nature Reviews Molecular Cell Biology 17: 399-412. PubMed abstract
2. Higashi, T.L. and Uhlmann, F. (2022)
SMC complexes: Lifting the lid on loop extrusion.
Current Opinion in Cell Biology 74: 13-22. 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. 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
5. Pirincci Ercan, D., Chrétien, F., Chakravarty, P., Flynn, H.R., Snijders, A.P. and Uhlmann, F. (2021)
Budding yeast relies on G1 cyclin specificity to couple cell cycle progression with morphogenetic development.
Science Advances 7: eabg0007. PubMed abstract