The driving forces of cell division
At the onset of division the cell forms a spindle, a micro-machine made of microtubules, which divide the chromosomes by pulling on kinetochores, protein complexes on the chromosome. The central question in the field is how accurate chromosome segregation results from the interactions between kinetochores, microtubules and the associated proteins.
According to the current paradigm, the forces on kinetochores are produced by k-fibers, bundles of microtubules extending between the spindle pole and the kinetochore. The proposed project is built upon a hypothesis that a new class of microtubules, which we term bridging microtubules, bridge sister kinetochores.
Our preliminary results show that bridging microtubules are responsible for the positioning of kinetochores in HeLa and PtK1 cells. By applying cutting-edge microscopy and laser microsurgery techniques, we will determine the organization of bridging microtubules, identify the proteins that link them with k-fibers, and uncover where and how the forces for kinetochore positioning and movement are generated.
We will take an interdisciplinary approach by combining laser microsurgery with genetic perturbations, quantitative measurements of the responses and comparison with theoretical models. Understanding the role of bridging microtubules in force generation and chromosome movements will not only shed light on the mechanism of chromosome segregation, but may also increase the potential of mitotic anticancer strategies, as the spindle is a major target for chemotherapy.
Research area: Cellular and Developmental Biology
Researcher: Prof Iva Tolić
Host Institution: Ruđer Bošković Institute, Zagreb
Project: A new class of microtubules in the spindle exerting forces on kinetochores (NewSpindleForce)
ERC call: Consolidator Grant 2014
ERC funding: € 2.15 million for five years