To maintain genetic integrity, eukaryotic cells must duplicate their chromosomes and subsequently segregate them to daughter cells when they divide and proliferate. The unraveling of the mechanisms for chromosome segregation should improve our understanding of various human diseases such as cancers and congenital disorders, which are characterized by chromosome instability and aneuploidy. In this project, we will study mechanisms of chromosome segregation using quantitative and interdisciplinary approaches. We will combine expertise in molecular genetics, biochemistry, nanotechnology and biophysics, to study the dynamic process of chromosome segregation.
Tanaka’s group has been studying how chromosomes associate correctly with the mitotic spindle. This association is mediated by kinetochore–microtubule interaction, which provides a driving force for chromosome segregation in cells . They use human cells and budding yeast as model systems to discover fundamental principles of chromosome segregation (e.g. ). Meanwhile, McGloin’s group has expertise in optical tweezers and particle dynamics (e.g. ). The two groups are collaborating to reconstitute kinetochore–microtubule interactions in vitro using bioactive proteins and nanotechnology. They are also building optical tweezers to measure and characterize the forces applied on this interaction.
The PhD student, taking this project, will use these techniques to analyze the kinetochore–microtubule interaction. They will receive training in both the biological aspects of the project and on the use of high-resolution optical tweezers and force spectroscopy. This project will reveal fundamental mechanisms ensuring genetic integrity of cells, and will provide a PhD student with a unique opportunity to learn and combine techniques in molecular genetics, biochemistry, nanotechnology and biophysics.
1. Tanaka, T.U. (2010). Kinetochore-microtubule interactions: steps towards bi-orientation. The EMBO journal 29, 4070-4082.
2. Kalantzaki, M., Kitamura, E., Zhang, T., Mino, A., Novak, B., and Tanaka, T.U. (2015). Kinetochore-microtubule error correction is driven by differentially regulated interaction modes. Nature cell biology 17, 530.
3. McDonald, C., McDougall, C., Rafailov, E., and McGloin, D. (2014). Characterizing conical refraction optical tweezers. Optics letters 39, 6691-6694.