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CREF TALK

November 16th, 2023  – 2.30 pm

Phase transitions in the nucleus of cells shape genome folding and function

Mario Niccodemi, Department of Physics, University of Naples “Federico II” and INFN, Naples, Italy.

In the nucleus of cells, the human genome has a complex 3D organization that serves vital functional purposes as, for instance, our genes, to be activated, need to contact distal regulatory regions along DNA [1]. Yet, it is largely unknown how the system is orchestrated. I discuss, first, our new technologies to map those contacts and, next, our results from polymer physics [1-6], confirmed by molecular biology experiments [6-8], showing that chromosome 3D architecture is controlled by phase transitions, such as micro-phase separations or coil-globule transitions. Those results ground the comprehension of the very functioning of our genome on the principles of physics. They can be successfully employed to predict, for example, how gene-neutral mutations result in diseases, such as congenital disorders and cancer, by altering the regulatory network of genes [3,9-11].

[1] R.A. Beagrie, A. Scialdone, …, M. Nicodemi, A. Pombo. Nature 543, 519 (2017). [2] M. Barbieri, M. Chotalia, …, M. Nicodemi, PNAS 109, 16173 (2012)
[3] S. Bianco, D.G. Lupianez, A.M. Chiariello, …, M. Nicodemi. Nature Genetics 50, 662 (2018).
[4] M. Conte, L. Fiorillo, S. Bianco, …, M. Nicodemi. Nature Commun. 11, 3289 (2020).
[5] M. Conte, …, M. Nicodemi., Nature Commun. 13, 4070 (2022).
[6] M. Barbieri, S.Q. Xie, …, M. Nicodemi, A. Pombo. Nature Struct. Mol. Bio, 24, 515 (2017).
[7] L. Fiorillo, F. Musella, M. Conte, …, M. Nicodemi. Nature Methods 18, 482 (2021).
[8] W. Winick-Ng, …, M. Nicodemi, L. Welch, G. Castelo-Branco, A. Pombo. Nature 599, 684 (2021).
[9] B.K. Kragesteen, M. Spielmann, …, M. Nicodemi, S. Mundlos, G. Andrey. Nature Gen. 50, 1463 (2018).
[10] R.A. Beagrie, …, M. Nicodemi, A. Pombo. Nature Meth 20, 1037 (2023).
[11] G.I. Dellino, …, M. Nicodemi, N. Crosetto and P.G. Pelicci. Nature Genetics 51, 1011 (2019).