Functional membraneless organelles formed by de novo proteins

ORAL

Abstract

Protein phase transitions in biology are associated with disease pathogenesis, for example in cataract disease or sickle cell anaemia, but they also occur as part of normal biological processes, such as liquid-liquid phase separation in cells. While protein phase behaviour has been understood from a physics perspective for globular proteins for some time, how we can apply what we already know to biomolecular condensation, or the phase transitions of other protein types is less clear. In my talk, I will describe the design of genetically encoded de novo polypeptides that form membraneless organelles in Escherichia coli and how the designed polypeptide can co-compartmentalize a functional enzyme pair, to create functional membraneless organelle with product formation close to the theoretical limit.

* This work was funded by the Leverhulme Trust through a grant to J.J.M. and D.N.W. (RGP-2021-049). R.O. was funded through a European Union’s Horizon 2020 research and innovation programme Marie Skłodowska-Curie grant (NovoFoldno.795867). A.T.H. and D.N.W. are funded by the University of Bristol through the Max Planck-Bristol Centre for Minimal Biology.

Publication: A. T. Hilditch, A. Romanyuk, Stephen J. Cross, R. Obexer*, J.J. McManus*, D. N. Woolfon*, Assembling membraneless organelles from de novo designed proteins, Nature Chemistry, DOI: 10.1038/s41557-023-01321-y (2023).

Presenters

  • Jennifer J McManus

    University of Bristol

Authors

  • Jennifer J McManus

    University of Bristol

  • Alexander T Hilditch

    University of Bristol

  • Andrey Romanyuk

    University of Bristol

  • Ragesh Kumar Thelakkadan Puthiyaveettil

    University of Bristol

  • Stephen J Cross

    University of Bristol

  • Richard Obexer

    University of Manchester

  • Derek N Woolfson

    University of Bristol