About the Project
Our lab focuses on understanding the processes which lead to a reshaping of the nuclear compartment in health and disease.
The nucleus is continuously reshaped by the cytoskeletal filaments that surround it. Human cells exploit this (cancer, gametes, mesenchymal, immune) by changing their nuclear-cytoskeletal architecture to suit their function.
Our final goal is to understand how the cytoskeleton filaments works in concert to shape the nucleus, allowing cell migration, tissue formation, cancer progression and immune response. Nucleus-cytoskeleton organisation is in fact often altered in human pathologies like ageing, developmental disorders, and cancer, where nuclear deformability is a determinant of metastatic capacity.
We know the components, but what we lack is their structure: how these filaments form high-order networks, how they are anchored and mechanically coupled at the nuclear surface at atomic resolution and in the cellular context is unknown. The structure would allow us to understand the mechanistic principles behind high-order cytoskeleton architecture involved in nuclear remodelling and would therefore contribute to finding solutions to mitigate diseases like cancer metastatic progression.
The PhD project is multifaceted between structural and cell biology cutting-edge methods (electron cryo-tomography, single particle cryo-EM, super resolution light microscopy, correlative light and electron microscopy, live cell imaging) with the main aim being to determine the high-resolution structure of cytoskeletal filaments coating the nucleus in conditions like confinement / migration / stretching and to define how the network architecture reorganises in different conditions.
The PhD project will involve joining an extremely motivated and agile team with an interdisciplinary mentality and will get the support of the electron and light microscopy facilities, mechanical and electronics workshops, and collaborations with group leaders across LMB units.
Funding Notes
References
- Zimmerli C, Allegretti M et al, Science 2021. Nuclear pores dilate and constrict in cellulo. DOI:10.1126/science.abd9776
- Santos dos A, Knowles O, Dendooven T, Hale T, Hale VL, Burt A, Kolata P, Cannone G, Bellini D, Barford D, Allegretti M. BioRxiv 2024. Human spermatogenesis leads to a reduced nuclear pore structure and function. DOI: 10.1101/2024.10.30.620797
- Dendooven T, Ebrahimi M, dos Santos A, Dhondt W, Knowles O, Hale T, Burt A, Mehdipour AR, Allegretti M. BioRxiv 2025. In-cell structure of a LINC complex reveals the molecular basis for membrane remodelling and head-to-tail coupling in sperm cells. DOI: 10.1101/2025.08.04.668116
- Hale T, Hale VL, Kolata P, Santos, Allegretti M. J Cell Science 2026. Paclitaxel compromises nuclear integrity in interphase through SUN2-mediated cytoskeletal coupling. DOI: 10.1101/2025.01.17.633376
- Kolata P, dos Santos A, Knowles O, Dendooven T, Allegretti M. Nat Struct Mol Biol 2026. Molecular architecture and spatial organisation of proteasomes in the human sperm nucleus. DOI:10.64898/2025.12.16.694293
- So-Last M, Burt A, Hale T, Allegretti M. BioRxiv 2026. Easymode: general pretrained networks for cellular cryo-ET enable flexible approaches to subtomogram averaging. DOI:10.64898/2026.05.19.726344
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