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Home > The macromolecular basis of nuclear reshaping in humans
Matteo Allegrettiss

Matteo Allegretti

The macromolecular basis of nuclear reshaping in humans

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Our lab focuses on understanding the processes which lead to a remodelling of the nuclear compartment in health and disease.

In particular we look at how developmental or mechanical stimuli triggering pathways of reshaping. Our final goal is to understand how macromolecules work in concert to shape the nucleus, regulate nucleocytoplasmic transport and influence expression.

The cell nucleus contains the genetic information, while the cytoskeleton is the fundamental scaffold of eukaryotic cells, controlling cellular and organellar shape. The interaction nucleus-cytoskeleton is one of the most important in maintaining cellular homeostasis and it is in fact often altered in human pathologies. The understanding of the mechanistic principles of cytoskeleton organization involved in nuclear remodelling would therefore contribute to find solutions to mitigate diseases like developmental disorders and cancer metastatic progression.

The project is multifaceted with the main aims to: determine proteins architectural changes during nuclear deformation by mechanical stress, or during early development; and develop and build new tools to achieve the above goals.

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 of the collaborations with group leaders across LMB units.

References

In-cell architecture of the nuclear pore and snapshots of its turnover
Allegretti M, Zimmerli CE, Rantos V, Wilfling F, Ronchi P, Fung HKH, Lee CW, Hagen W, Turoňová B, Karius K, Börmel M, Zhang X, Müller CW, Schwab Y, Mahamid J, Pfander B, Kosinski J, Beck M
Nature 586(7831): 796-800 (2020)
 
Nuclear pores dilate and constrict in cellulo
Zimmerli CE, Allegretti M, Rantos V, Goetz SK, Obarska-Kosinska A, Zagoriy I, Halavatyi A, Hummer G, Mahamid J, Kosinski J, Beck M
Science 374(6573): (2021)
 
In-cell structure of a LINC complex reveals the molecular basis for membrane remodelling and head-to-tail coupling in sperm cells
Dendooven T, Ebrahimi M, dos Santos A, Dhondt W, Knowles O, Hale T, Burt A, Mehdipour AR, Allegretti M
bioRxiv: (2025) preprint
 
Nuclear disruption as a mechanism of the chemotherapeutic drug paclitaxel in interphase
Hale T, Hale VL, Kolata P, Santos , Allegretti M
bioRxiv: (2025) preprint
 
Human spermatogenesis leads to a reduced nuclear pore structure and function
Santos , Knowles O, Dendooven T, Hale T, Hale VL, Burt A, Kolata P, Cannone G, Bellini D, Barford D, Allegretti M
bioRxiv: (2024) preprint
 
Honeycomb gold specimen supports enabling orthogonal focussed ion beam-milling of elongated cells for cryo-ET
Hale VL, Hooker J, Russo CJ, Löwe J
Journal of Structural Biology 216(2): 108097 (2024)

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