PhD Studentship- Uncovering the chemical origin of lipid membrane diversity (3.5 years Fixed Term)

A fully funded 3.5-year PhD studentship, supported by an LCLU Joint Collaborative Programme grant, is available in the ProtocellLab (www.bonfiolab.eu ) at the Department of Biochemistry commencing on 1 October 2024.

Summary:The origin of cell membranes is a major unresolved issue in evolution. Evolutionary biology points to the existence of primitive cells with compositionally diverse membranes. However, the assumption that such lipid diversity is dependent upon enzymatic chemistry has generated models comprising compositionally minimal membranes (binary or ternary mixtures of short-chain fatty or phosphatidic acids). This project aims to reconcile biology and chemistry by challenging the critical limiting assumption that lipid diversity cannot be achieved through non-enzymatic chemistries. The project will lead to a fundamental understanding of the origins of lipid diversity, including the features now associated with bacterial and archaeal lipids; new strategies based on compositionally diverse membranes to probe, sense or replicate cellular behaviours; and a deep-rooted understanding of the emergence and evolution of cellular processes at the molecular level.

Background: While prebiotic pathways to all four RNA nucleotides and most of the twenty biological amino acids have been proposed, only a few non-enzymatic routes to modern lipids have been described. As such, prebiotic chemistry has yet to address models of primitive membranes comprising the vast structural diversity of modern lipids. However, if lipid diversity is an essential feature of modern membranes, can non-enzymatic chemistry be harnessed to generate lipid diversity?

Approach: To identify the set of diverse lipids that could have been formed non-enzymatically on early Earth, the student will adapt diversity-oriented synthetic strategies to prebiotic chemistry by transforming primitive lipids into modern lipids through non-enzymatic chemical strategies. The student will design and develop novel synthetic methods to generate libraries of lipids using a combination of solution-phase, membrane-templated and dry-state chemistries. The supramolecular properties of synthetic lipids and their biophysical features will be evaluated by fluorescence spectroscopy, dynamic light scattering, and light and electron microscopy. Additionally, encapsulated prebiotic reactions, such as RNA replication and protometabolic processes, will be investigated to better understand the chemistry of bioinspired systems.

ProtocellLab: The main focus of the ProtocellLab is to understand how primitive cells emerged on early Earth and how they started to interact with one another. The group is moving to the Department of Biochemistry in June 2024. The PhD student will develop skills in the areas of prebiotic, systems and supramolecular chemistry, applied to primitive and artificial cells. The small group size (5 PhD students and 2 PDRAs) ensures close supervision and training. The project offers interactions with other groups within the Leverhulme Centre for Life in the Universe, with the possibility of performing research periods abroad.

Fixed-term: The funds for this post are available for 3.5 years in the first instance.

Application. To apply, please e-mail Dr Claudia Bonfio ([email protected] ) with the following information by 29 March 2024:

• CV (max two pages), with full contact details of 2 academic referees.
• Motivation letter (max two pages) highlighting (a) your research interests, (b) what you hope to achieve from the programme, and (c) why you wish to undertake this PhD.

Please note that applicants are also required to officially apply to the University using the Applicant Portal: http://www.graduate.study.cam.ac.uk/how-do-i-apply by the deadline of 29 March 2024. Please search in the Course Directory for 'Biochemistry' PhD (Course Code: BLBI22) as the programme of study. Applicants should indicate on the application form that they wish to apply for other sources of funding.

Any questions regarding the application process should be directed to the Postgraduate Admissions Administrator at [email protected] .

This studentship is open to UK citizens or UK nationals or have a settled/pre-settled status only.

The studentship is open to those eligible for the 'Home' rate of University fees. Further information on how your fee status is determined can be found at the link below: https://www.postgraduate.study.cam.ac.uk/finance/fees/what-my-fee-status .

Please quote reference PH40713 on your application and in any correspondence about this vacancy.

The Protocell Lab and the University actively support equality, diversity and inclusion and encourage applications from all sections of society. We place major emphasis on the importance of teamwork and an enjoyable work environment as a foundation for performing internationally leading research. This will allow the student to acquire cutting-edge research methodologies in a supportive environment where they can focus on making the best possible scientific progress.