Claudia Bonfio(2)

Unlocking primitive cell division
Lead Supervisor: Claudia Bonfio, Department of Biochemistry
Co-supervisor: Katherine Stott, Department of Biochemistry

Brief summary
This project aims at assembling primitive cells capable of division in the absence of modern biochemical machinery. Our lab has so far focused on the ability of primitive lipids to organise in different lipid domains. We now aim to employ primitive coacervates to modulate the surface area-to-volume of primitive liposomes, ultimately leading to division. This project will provide:
i) an understanding on the molecular features that govern interactions between membrane-less and membrane-bound compartments,
ii) a library of coacervates able to affect the surface area-to-volume of liposomes
iii) optimised protocols for the spectroscopic characterisation and imaging of primitive cell models.

Importance of the area of research concerned
Throughout evolution, modern cells have developed sophisticated machinery to precisely divide their membrane-bound compartments and regulate them. Yet, the minimal set of cellular components available for primitive cells to drive their division is still unknown. This lack of understanding calls for fundamental studies seeking strategies for primitive cell division.

This project aims to address this knowledge gap by exploring the cooperative interactions between primitive compartments (i.e., membrane-bound and membrane-less compartments), and their impact on enzyme-free cellular division.

Our research will serve as a biochemical platform for probing the origin of cellular replication, and the principles leading to the emergence of living cells. Moreover, not only will this project explore the synergy between protocell models so far only considered antithetically. It will also offer a more complete picture of the transition from prebiotic chemistry to early life.

What will the student do?
The student will be able to develop biophysics and supramolecular chemistry skills, which can be applied to membrane-bound and membrane-less model compartments (i.e., liposomes and biomolecular condensates). Specifically, the student will investigate the compatibility of complex coacervates, made of short oligonucleotides and positively-charged peptides, and lipid membranes, composed of primitive lipids (e.g., medium-chain fatty acids, phosphatidic acids and more complex phospholipids). The student will design and develop real-time spectroscopy- and imaging-based protocols to study the  interactions between different primitive cell models. The project offers interactions with other groups across multiple departments, including Prof. Lorenzo Di Michele, Dr. Phil Holliger and Prof. Rosana Collepardo-Guevara.

References
Hargreaves W., Mulvihill S. and Deamer D. - Synthesis of phospholipids and membranes in prebiotic conditions. Nature 266, 78-80 (1977). https://doi.org/10.1038/266078a0
Bonfio C., Russell D.A., Green N.J., Mariani A. and Sutherland J.D. - Activation chemistry drives the emergence of functionalised protocells. Chem Sci. 11, 1068810697 (2020). https://doi.org/10.1039/D0SC04506C
Lloyd C.T., Iwig D.F., Wang B. et al. - Discovery, structure and mechanism of a tetraether lipid synthase. Nature 609, 197–203 (2022). https://doi.org/10.1038/s41586-022-05120-2 Releva

Requirements as to the educational background of candidates that would be suitable for the project
Due to the nature of the project, an undergraduate degree in chemistry or biochemistry is required. The student should have an interest in supramolecular or biophysical chemistry, or artificial cell design and development.

Applying
You can find out about applying for this project on the Leverhulme Centre for Life in the Universe widening participation PhD Studentships page.