The Nuclear Dynamics Group investigates how cells attempt to re-organise cellular architecture to resolve threats on genome stability. We use highly specialised techniques, including super-resolution microscopy and live cell imaging, to track changes in the structure and movement of molecules within the nuclei of cells.
The nucleus is a dynamic entity required to maintain genome integrity by facilitating repair of the genetic material when needed. The most prominent challenge for genome integrity is the DNA replication process, whose complexity renders genome copying susceptible to endogenous and exogenous threats. Any process hindering replication is referred to as "replication stress," and the cellular processes that countervail replication threats are the "replication stress response". Most of the genome instability that drives cancer development results from replication stress. Consequently, cancer cells typically suffer from endogenous replication stress and rely heavily on the replication stress response for survival. The main goal of our lab is to understand how cancer cells' unique stress response and nuclear dynamics allow tumour progression and drug resistance.
Our lab is interested in identifying the structural, architectural, and physical nuclear alterations that occur in response to replication stress and understanding how these alterations facilitate the regulation of DNA repair in time and space. Our over-arching aim is to integrate cutting-edge basic research with translational approaches to identify, validate, and target specific regulators of nuclear dynamics in response to DNA replication stress. Specifically, our lab employs diverse experimental strategies and various techniques, including biochemistry, proteomics, live-cell imaging, super-resolution microscopy, bespoke image analysis tools and DNA combing analysis to gain conceptual advances in nuclear biology.
Come work with us on nuclear dynamics, DNA damage and repair, and cancer development. We are currently recruiting for the positions of:
- Honours Student
- PhD Student - CMRI offers a competitive PhD Research Award, providing a top-up on other PhD scholarships. Applications are open all year; more details about the application process can be found on the CMRI Research Awards page. For further information, contact the CMRI Postgraduate student coordinator ([email protected]).
- Postdoctoral fellow
Interested applicants should submit CV and Cover Letter to Dr Noa Lamm-Shalem: [email protected].
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Dr Lamm is the Head of the Nuclear Dynamics Group at the Children's Medical Research Institute (CMRI). Potential PhD applicants should contact Dr Lamm for specific project details.
Selected Publications and Reviews
Three-dimensional chromatin organization shapes origin activation and replication fork directionality.
Giles, K.A., Lamm, N., Taberlay, P.C., and Cesare, A.J. (2022). bioRxiv, 2022.2006.2024.497492.
Nuclear F-actin counteracts nuclear deformation and promotes fork repair during replication stress.
Lamm, N., Read, M.N., Nobis, M., Van Ly, D., Page, S.G., Masamsetti, V.P., Timpson, P., Biro, M., and Cesare, A.J. (2020). Nat Cell Biol 22, 1460-1470.
Full length RTEL1 is required for the elongation of the single-stranded telomeric overhang by telomerase.
Awad, A., Glousker, G., Lamm, N., Tawil, S., Hourvitz, N., Smoom, R., Revy, P., and Tzfati, Y. (2020). Nucleic Acids Res 48, 7239-7251.
Replication stress conferred by POT1 dysfunction promotes telomere relocalization to the nuclear pore.
Pinzaru, A.M., Kareh, M., Lamm, N., Lazzerini-Denchi, E., Cesare, A.J., and Sfeir, A. (2020). Genes Dev 34, 1619-1636.
Replication stress induces mitotic death through parallel pathways regulated by WAPL and telomere deprotection.
Masamsetti, V.P., Low, R.R.J., Mak, K.S., O'Connor, A., Riffkin, C.D., Lamm, N., Crabbe, L., Karlseder, J., Huang, D.C.S., Hayashi, M.T., et al. (2019). Nat Commun 10, 4224.
Genomic Instability in Human Pluripotent Stem Cells Arises from Replicative Stress and Chromosome Condensation Defects.
Lamm, N., Ben-David, U., Golan-Lev, T., Storchova, Z., Benvenisty, N., and Kerem, B. (2016). Cell Stem Cell 18, 253-261.
Review: Chromatin mobility and relocation in DNA repair.
Lamm, N., Rogers, S., and Cesare, A.J. (2021). Trends Cell Biol 31, 843-855.
Review: The mTOR pathway: Implications for DNA replication.
Lamm, N., Rogers, S., and Cesare, A.J. (2019). Prog Biophys Mol Biol 147, 17-25.