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Direct observation of the structure and function of cooperatively assembled membrane spanning pores formed by antimicrobial peptides


Project Description

This project will combine multiple single molecule imaging techniques applied to model membranes [1] to study the mechanisms of peptide interaction of established and novel AMPs. By studying at the single molecule level we can gain otherwise inaccessible insight into the mechanisms of assembly of membrane spanning pores.
With this approach you will study the synergistic activity of Magainin-II/PGLa by quantitative three-colour single-molecule imaging to understand the nature of peptide-peptide interactions [2] in pore formation, and quantify the activity dynamics of assembled pores [3]. You will also extend these techniques to novel AMPs developed by the team [4]. Understanding the mechanism of action of such pores will provide fundamental understanding into molecular self-assembly, alongside determining structure-function relationships of the pore itself, fundamental to design novel AMPs. The tested peptides possess cytotoxic activity against cancer cells, so this research may create opportunities for next generation therapeutics and drug delivery systems. Once peptide characterisation is achieved in model membranes you will have the opportunity to study their effect in 2-and-3D cell models.
Research Environment: You will work within a multidisciplinary team at the physical-life science interface, gaining experience across disciplines from biochemistry, single molecule techniques, membrane synthetic biology and cell biology. You will initiate the research with rotational projects of peptide and protein synthesis (Jin), and single molecule membrane imaging (Castell), providing a foundation for the research project. The supervisory team have an excellent track record in supervision and publication, alongside a unique combination of expertise from which you and the project will benefit, - e.g. artificial membranes and single molecule methods (Castell), protein/peptide biochemistry (Jin), AMPs and cell biology (Jones) and tissue model and biological imaging (Watson). We applications from enthusiastic scientists with appropriate knowledge/experience/ideas in some of the areas outlined (biochemistry

protein/peptide handling

biological physics

physical chemistry

fluorescence) with an eagerness to learn across disciplines and develop in areas new to the candidate. We do not expect prior experience in all areas. Talented and enthusiastic candidates from all backgrounds are encouraged to apply. We recognise that diversity within a team provides a greater range of experience, perspectives and ideas to draw upon when tackling problems and informing decisions.
Training and Development Opportunities: You will gain skills across the physical and life-sciences. You will develop a number of transferable research skills including experimental design, data analysis and scientific communication. You will benefit from a cohort experience within the Physics of Life Hub and benefit from participation in regular research meetings and journal clubs of the supervisory labs, alongside University seminars, training events and post-graduate research days. You will have the opportunity to engage and collaborate with wider research in the investigators’ laboratories, including H2020 project AC/DC concerning membrane based artificial cells (Castell) and opportunities to engage with industry through supervisory collaborative networks, e.g. CALIN Network (Jones/Watson). You will have the opportunity to present your findings at international conferences and publish in high impact journals. Students from the supervisory labs have taken up positions in highly regarded academic institutions and companies.

Funding Notes

EPSRC funded DTP PhD Studentship within the Interdisciplinary Doctoral Training Hub “Physics of Life”

This is a fully-funded studentship which includes fees, stipend and a research and training support grant, for 3.5 years at UKRI rate, for home/EU students.

Self-funded international students are also welcomed to apply.

Applicants should possess (or expect to obtain) a UK higher education degree, or a non-UK qualification recognised by the University as being equivalent to this. Normally you will be required to have the equivalent of a 2:1 or above.

Details of accepted English Language qualifications for admissions can be found here View Website

References

The Hub is designed as a cross-disciplinary PhD research and training programme at the physics/life science interface. Students will benefit from joint supervision across the Colleges of Physical Sciences and Life Sciences at Cardiff University. Each project commences with two 3-months stages in the labs of the joint supervisors. The Hub will offer cohort development opportunities through joint research meetings, a “Physics of Life” summer school in 2022, and a student-led workshop in 2023. Students will be part of a vibrant, interactive community, sharing monthly newsletters and connected via a dedicated portal. Each student will be supported by a mentor. The Physics of Life Doctoral Training Hub aims to equip PhD candidates with multidisciplinary research skills that are highly sought after in academic and industry.

[1] OK Castell et al. Methods 147 221-228 (2018)
[2] PM Dijkman et al. Nature Communications 9 1-14 (2018)
[3] S Huang et al. Nature Nanotechnology 10 986-991 (2015)
[4] N Eissa et al. Biochemical Journal 477 45-60 (2020)

How good is research at Cardiff University in Allied Health Professions, Dentistry, Nursing and Pharmacy?

FTE Category A staff submitted: 74.95

Research output data provided by the Research Excellence Framework (REF)

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