We have a vacancy for a PhD candidate to work on the project ‘Enzymatically controlled membrane attachment and exocytosis of condensates in synthetic cells’. The project is part of ComeInCell, the EU Doctoral Network on Integrative Synthetic Cell Design (
https://www.comeincell.org): Condensates at Membrane Scaffolds – Integrated Systems as Synthetic Cell Compartments.
You will join the group of Evan Spruijt (
www.spruijtlab.com) at Radboud University and you will be given the opportunity to do secondments at the Max Planck Institute for Colloids and Interfaces in Potsdam, Germany (
Dimova Group), the University of Groningen in the Netherlands (
Poolman Group), the Heinrich Heine Universität Düsseldorf in Germany (
Exterkate Group) and the Centro de Investigaciones Biologicas Margarita Salas of CSIC in Madrid, Spain (
Rivas Group). Synthetic cells hold great promise in the development of innovative therapeutic strategies. However, molecular payloads synthesised inside synthetic cells must be secreted and new molecular building blocks or drugs must be delivered to synthetic cells in a smart and programmable way. Condensates have recently been shown to interact with membranes in a rich and dynamic way, including the possibility of entering giant unilamellar vesicles (GUVs) via endocytosis. In this project, you will develop synthetic cells and condensates that exhibit a tunable affinity for the GUV inner membrane. The membrane affinity will be controlled via biochemical pathways that regulate ATP levels and that regulate the self-organisation of protein filaments. Enzyme-controlled condensates will be directed to the membrane, where condensate property modulation and membrane remodelling are used to directly uptake or secrete condensates through membrane wrapping to deliver biomolecular payloads concentrated inside the condensates. This may enable future use of synthetic cells for the development of RNA and protein-based therapeutics.
You will communicate your findings in papers in peer-reviewed journals and at international conferences. You will also be involved in training and teaching BSc and MSc students.
Selected References:
- S. Javed, E. Spruijt, Spontaneous wrapping of coacervates by lipid bilayers upon heat shock creates resilient and intact membranized coacervates, ChemRxiv (2024); DOI 10.26434/chemrxiv-2024-f4gls
- T. Lu, S. Liese, L. Schoenmakers, C.A. Weber, W.T.S. Huck and E. Spruijt, Endocytosis of coacervates into liposomes, J. Am. Chem. Soc. 144 (30), 13451-13455 (2022); https://doi.org/10.1021/jacs.2c04096
- M. Abbas, W.P. Lipinski, K.K. Nakashima, W.T.S. Huck and E. Spruijt, A short peptide synthon for liquid-liquid phase separation, Nature Chemistry 13, 1046-1054 (2021); https://www.nature.com/articles/s41557-021-00788-x
- K.K. Nakashima, M.H.I. van Haren, A.A.M. André, I. Robu and E. Spruijt, Active coacervate droplets are protocells that grow and resist Ostwald ripening, Nature Commun. 12, 3819 (2021); https://doi.org/10.1038/s41467-021-24111-x