Engineering dynamic, functional membrane interfaces for artificial cells

PGR-P-1786

Key facts

Type of research degree: PhD
Application deadline: Ongoing deadline
Country eligibility: International (open to all nationalities, including the UK)
Funding: Non-funded
Supervisors: Professor Paul Beales and Dr Arwen Tyler
Schools: School of Chemistry

<h2 class="heading hide-accessible">Summary</h2>

Engineering biological systems is considered to be one of the defining technologies of the 21st century with the potential for disruptive innovations in a wide range of industry sectors. A key underpinning concept in this field is the bottom-up design and assembly of artificial cells: novel, cell-like materials with integrated biomimetic functions. This enables the engineering of artificial cells that replicate a cell’s ability to sense and respond to complex signals within their environment, utilise internal (bio)chemical computation and manufacture processes, and initiate collective responses in a community of artificial cells. To enable the full potential of engineering biology, the underpinning tools and technologies for engineering artificial cells needs to be expanded. This project will combine biological and synthetic components to create mechanically robust artificial cells that exhibit dynamic membrane-driven functions of fission (cf. cell division), fusion (cf. signal trafficking) and compartmentalisation (cf. organelle formation). The fundamental mechanisms of these processes will be studied in order to facilitate control over these dynamic processes and enable their use within the framework of engineering design. These dynamic functions will be integrated within a signalling cascade to demonstrate how these processes can be initiated as part of a signal response network in an artificial cell towards incorporating these functions within engineering biology solutions to meet industrial challenges.

<h2 class="heading hide-accessible">Full description</h2>

We have previously contributed to the toolbox for engineering artificial cells by developing hybrid membranes with enhanced stability and durability (1,2), demonstrating new methods for functionalising membranes with integral protein nanomachines (3), designing biological (4) and synthetic, biomimetic (5,6) strategies to control dynamic structural transformations in membranes, and encapsulating feedback-controlled processes and inter-cellular signalling mechanisms (7). Future challenges lie in the integration of these approaches to create engineering biology solutions to industry challenges in sectors such as biomedical diagnostics and therapies (8), environmental remediation, clean growth and sustainable agriculture. References: (1) Khan S., Li M., Muench S.P., Jeuken L.J.C. and Beales P.A.; Durable Proteo-Hybrid Vesicles for the Extended Functional Lifetime of Membrane Proteins in Bionanotechnology. Chem. Commun. 52, 11020 - 11023 (2016) (2) Seneviratne R., Coates G., Xu Z., Cornell C.E., Thompson R.F., Sadeghpour A., Maskell D.P., Jeuken L.J.C, Rappolt M. and Beales P.A.; High resolution membrane structures within hybrid lipid-polymer vesicles revealed by combining x-ray scattering and electron microscopy. Small 19, 2206267 (2023) (3) Catania R., Machin J., Rappolt M., Muench S.P., Beales P.A. and Jeuken L.J.C.; Detergent-Free Functionalisation of Hybrid Vesicles with Membrane Proteins Using SMALPs. Macromolecules 55(9), 3415–3422 (2022) (4) Booth A., Marklew C.J., Ciani B. and Beales P.A.; In vitro membrane remodelling by ESCRT is regulated by negative feedback from membrane tension. iScience 15, 173-184 (2019) (5) Arribas Perez M. and Beales P.A.; Biomimetic curvature and tension-driven membrane fusion induced by silica nanoparticles. Langmuir 37(47), 13917–13931 (2021) (6) Xu Z., Rappolt M., Tyler A.I.I. and Beales P.A.; Cubosome-Induced Topological Transformations in Giant Vesicles. ChemRxiv (2022) (7) Miele Y., Jones S.J., Rossi F., Beales P.A. and Taylor A.F.; Collective Behavior of Urease pH Clocks in Nano- and Microvesicles Controlled by Fast Ammonia Transport. J. Phys. Chem. Lett. 13, 1979–1984 (2022) (8) Jones S.J., Taylor A.F. and Beales P.A.; Towards feedback-controlled nanomedicines for smart, adaptive delivery. Experimental Biology and Medicine 244, 283-293 (2019)

<h2 class="heading">How to apply</h2>

Formal applications for research degree study should be made online through the <a href="https://www.leeds.ac.uk/research-applying/doc/applying-research-degrees">University's website</a>. Please state clearly in the Planned Course of Study section that you are applying for PHD Chemistry FT, in the research information section that the research degree you wish to be considered for is Engineering dynamic, functional membrane interfaces for artificial cells as well as <a href="https://eps.leeds.ac.uk/chemistry/staff/4203/professor-paul-beales">Professor Paul Beales</a> as your proposed supervisor and in the finance section, please state clearly the funding that you are applying for, if you are self-funding or externally sponsored. If English is not your first language, you must provide evidence that you meet the University's minimum English language requirements (below). As an international research-intensive university, we welcome students from all walks of life and from across the world. We foster an inclusive environment where all can flourish and prosper, and we are proud of our strong commitment to student education. Across all Faculties we are dedicated to diversifying our community and we welcome the unique contributions that individuals can bring, and particularly encourage applications from, but not limited to Black, Asian, people who belong to a minority ethnic community, people who identify as LGBT+ and people with disabilities. Applicants will always be selected based on merit and ability. Applications will be considered on an ongoing basis.  Potential applicants are strongly encouraged to contact the supervisors for an informal discussion before making a formal application.  We also advise that you apply at the earliest opportunity as the application and selection process may close early, should we receive a sufficient number of applications or that a suitable candidate is appointed. Please note that you must provide the following documents in support of your application by the closing date of 3 April 2024 for Leeds Opportunity Research Scholarship or 8 April 2024 for Leeds Doctoral Scholarship: <ul> <li>Full Transcripts of all degree study or if in final year of study, full transcripts to date</li> <li>Personal Statement outlining your interest in the project</li> <li>CV</li> </ul>

<h2 class="heading heading--sm">Entry requirements</h2>

Applicants to research degree programmes should normally have at least a first class or an upper second class British Bachelors Honours degree (or equivalent) in an appropriate discipline. The criteria for entry for some research degrees may be higher, for example, several faculties, also require a Masters degree. Applicants are advised to check with the relevant School prior to making an application. Applicants who are uncertain about the requirements for a particular research degree are advised to contact the School or Graduate School prior to making an application.

<h2 class="heading heading--sm">English language requirements</h2>

The minimum English language entry requirement for research postgraduate research study is an IELTS of 6.0 overall with at least 5.5 in each component (reading, writing, listening and speaking) or equivalent. The test must be dated within two years of the start date of the course in order to be valid. Some schools and faculties have a higher requirement.

<h2 class="heading">Funding on offer</h2>

Self-Funded or externally sponsored students are welcome to apply. UK – The <a href="https://phd.leeds.ac.uk/funding/209-leeds-doctoral-scholarships-2022">Leeds Doctoral Scholarships</a> and <a href="https://phd.leeds.ac.uk/funding/234-leeds-opportunity-research-scholarship-2022">Leeds Opportunity Research Scholarship</a> are available to UK applicants (open from October 2023). <a href="https://phd.leeds.ac.uk/funding/60-alumni-bursary">Alumni Bursary</a> is available to graduates of the University of Leeds. Non-UK –The <a href="https://phd.leeds.ac.uk/funding/48-china-scholarship-council-university-of-leeds-scholarships-2021">China Scholarship Council - University of Leeds Scholarship</a> is available to nationals of China (now closed for 2024/25 entry). The <a href="https://phd.leeds.ac.uk/funding/73-leeds-marshall-scholarship">Leeds Marshall Scholarship</a> is available to support US citizens. <a href="https://phd.leeds.ac.uk/funding/60-alumni-bursary">Alumni Bursary</a> is available to graduates of the University of Leeds. Important:  Any costs associated with your arrival at the University of Leeds to start your PhD including flights, immigration health surcharge/medical insurance and Visa costs are not covered under this studentship. Please refer to the <a href="https://www.ukcisa.org.uk/">UKCISA</a> website for information regarding Fee Status for Non-UK Nationals.

<h2 class="heading">Contact details</h2>

For further information on the application process, please contact the Doctoral College Admissions by email to <a href="mailto:maps.pgr.admissions@leeds.ac.uk">maps.pgr.admissions@leeds.ac.uk</a> For further information on the project, please contact Professor Paul Beales by email to <a href="mailto:p.a.beales@leeds.ac.uk">p.a.beales@leeds.ac.uk</a>.