HRZZ ROMBOSPINDLE

Role of microtubule minus-end-binding proteins in orchestrating mitotic spindle geometry — ROMBOSpindle

The mitotic spindle is a biomechanical structure that drives the equal division of genetic material between daughter cells. It is composed of microtubules and associated proteins which, through a myriad of feedback loops and regulatory mechanisms, allow the structure to self-assemble, self-regulate, and self-transform throughout the process of mitosis. For the spindle to ensure the high level of fidelity required for successful cell division, it must establish and maintain a well-controlled geometry. It is known that proteins which regulate the dynamics of microtubule plus-ends in a length-dependent manner play a major role in setting spindle length and therefore geometry, but the role of microtubule minus-end dynamics and the proteins which regulate them remains unclear. In this project, we plan to study which mechanisms might be responsible for regulating the dynamics of microtubule minus-ends as well as the influence they have on spindle length. To this end, we will develop a model of the mitotic spindle that incorporates the relatively understudied motor proteins associated with the regulation of microtubule minus-end dynamics in addition to known elements such as motor proteins that regulate plus-end dynamics and those that drive microtubule sliding. Our preliminary results demonstrate the necessity of a mechanism that allows minus-end dynamics to vary throughout the process of mitosis. Further development of the model will address what specific properties should be possessed by the proteins which regulate minus-end dynamics and shed light on the physical mechanism by which they function. The model will also provide quantitative predictions that will help to test our hypotheses against existing experimental results and serve as predictions for future experiments. By investigating the role of minus-end regulation in setting spindle length, this project has the potential to broaden our understanding of spindle mechanics and guide future research directions.

Researcher (PI): Nenad Pavin
Host Institution (HI): University of Zagreb – Faculty of Science
Collaborators: Matko Glunčić (PI)
HRZZ call: Research Projects IP-2025-02
HrZZ funding: 147,400.00 EUR for three years
Project Number: IP-2025-02-9880
Duration: Start date: June 15th, 2026, End date: June 14th, 2029

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