How does molecular organisation become biological function?
Living systems are built from chemically ordinary molecules, yet through their organisation they acquire remarkable biological capabilities. Our research seeks to understand the principles by which molecular interactions organise to create biological function. We combine chemistry, structural biology, biophysics, and quantitative cell biology to uncover the organising principles that govern living systems.
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Molecular organisation inside cells
Cells organise many biochemical reactions within specialised intracellular compartments known as membraneless organelles. These dynamic assemblies, including nucleoli, germ granules, and stress granules, lack membrane boundaries and instead form through collective interactions predominantly between proteins and RNA.
Although these structures have been recognised for many years, understanding how their molecular organisation gives rise to biological function has remained a major challenge. Our research aims to bridge this gap by identifying how amino acid sequence encodes the interactions that drive intracellular organisation.
Although these structures have been recognised for many years, understanding how their molecular organisation gives rise to biological function has remained a major challenge. Our research aims to bridge this gap by identifying how amino acid sequence encodes the interactions that drive intracellular organisation.
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From protein sequence to cellular organisation
Our lab has developed quantitative model systems based on intrinsically disordered proteins to understand how protein sequence specifies collective molecular behaviour. Using structural biology, biophysics, and polymer theory, we investigate how weak molecular interactions drive self-assembly, generate distinct intracellular chemical environments, and give rise to emergent biochemical activities.
This work has helped establish molecular principles linking protein sequence to the organisation and behaviour of membraneless organelles. A major goal of our research is to understand why evolution has repeatedly adopted these mechanisms of molecular organisation.
Find out more about our work please contact us directly.
This work has helped establish molecular principles linking protein sequence to the organisation and behaviour of membraneless organelles. A major goal of our research is to understand why evolution has repeatedly adopted these mechanisms of molecular organisation.
Find out more about our work please contact us directly.
Selected publications
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Holland, J., Nott, T. J., & Aarts, D. G. A. L. (2025). Intrinsic hydrophobicity of IDP-based biomolecular condensates drives their partial drying on membrane surfaces. The Journal of Chemical Physics, 162(11), 115101. (link)
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Crabtree, M. D., Holland, J., Pillai, A. S., Kompella, P. S., Babl, L., Turner, N. N., Eaton, J. T., Hochberg, G. K. A., Aarts, D. G. A. L., Redfield, C., Baldwin, A. J., & Nott, T. J. (2023). Ion binding with charge inversion combined with screening modulates DEAD box helicase phase transitions. Cell Reports, 42(11), 113375. (link)
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Holland, J., Castrejón-Pita, A. A., Tuinier, R., Aarts, D. G. A. L., & Nott, T. J. (2023). Surface tension measurement and calculation of model biomolecular condensates. Soft Matter, 19(45), 8706–8716. (link)
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Holland J., Crabtree M.D., Nott T.J. 2020. In Vitro Transition Temperature Measurement of Phase-Separating Proteins by Microscopy. In: Kragelund B., Skriver K. (eds) Intrinsically Disordered Proteins. Methods in Molecular Biology, vol 2141. Humana, New York, NY. (link)
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Brady, J.P., Farber, P.J., Sekhar, A., Lin, Y.H., Huang, R., Bah, A., Nott, T.J., Chan, H.S., Baldwin, A.J., Forman-Kay, J.D. and Kay, L.E., 2017. Structural and hydrodynamic properties of an intrinsically disordered region of a germ cell-specific protein on phase separation. Proceedings of the National Academy of Sciences, p.201706197. (link)
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Nott, T.J., Craggs, T.D. and Baldwin, A.J., 2016. Membraneless organelles can melt nucleic acid duplexes and act as biomolecular filters. Nature Chemistry, 8(6), pp.569-575. (link) (pdf)
News and Views, Nature Chemistry (link) Editors choice, Science (link) F1000 recommended (link) Oxford Science Blog |
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Nott, T.J., Petsalaki, E., Farber, P., Jervis, D., Fussner, E., Plochowietz, A., Craggs, T.D., Bazett-Jones, D.P., Pawson, T., Forman-Kay, J.D. and Baldwin, A.J., 2015. Phase transition of a disordered nuage protein generates environmentally responsive membraneless organelles. Molecular Cell, 57(5), pp.936-947. (link) (pdf)
F1000 recommended (link) |
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Chen, C., Nott, T.J., Jin, J. and Pawson, T., 2011. Deciphering arginine methylation: Tudor tells the tale. Nature Reviews Molecular Cell Biology, 12(10), pp.629-642. (link)
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Nott, T.J., Kelly, G., Stach, L., Li, J., Westcott, S., Patel, D., Hunt, D.M., Howell, S., Buxton, R.S., O’Hare, H.M. and Smerdon, S.J., 2009. An intramolecular switch regulates phosphoindependent FHA domain interactions in Mycobacterium tuberculosis. Science Signaling, 2(63), pp.ra12. (link)
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