Approximately 30% of the proteins in a cell are membrane proteins, which represent more than 60% of all known drug targets and play a critical role in both infection and immunity. The organization of membrane proteins into complexes, their segregation in lipid domains, and their effect on membrane shape is known to influence processes such as intracellular transport, cell division, cell migration, and signal transduction. Despite this importance, understanding the underlying principles of protein organization and function directly in the membrane lipid environment is severely limited by the lack of non-invasive measurement techniques with suited spatio-temporal resolution and sensitivity.
We have recently developed  a novel optical imaging tool called interferometric gated off-axis reflectance (iGOR) microscopy, suitable for fast tracking of single unlabelled biomolecules in suspended bilayer membranes. It combines the sensitivity of iSCAT  with the field retrieval of off-axis interferometry . Notably, the technique enables the quantification of the elastomechanics of the lipid membrane, through measurement of topography and fluctuations. In this project you will apply iGOR to advance our knowledge regarding:
(i) The dynamics of phase separation and domain formation  in suspended synthetic model membrane systems (e.g. giant unilamellar vesicles) containing ternary lipid mixtures forming liquid ordered and disordered domains, recapitulating lipid rafts.
(ii) The function of the integral membrane protein P2X,  a cell-surface ion channel activated by extracellular ATP, leading to downstream signaling events affecting nerve transmission, pain sensation, inflammation, making them important drug targets.
(iii) Study of membrane spanning pores. There remain many unanswered questions about the mechanisms of multimeric membrane protein pore assembly, and subsequent function. This will be investigated using iGOR in minimal model membrane systems .
(iv) Docking and trans-membrane transport mechanisms of viral particles. Viral infection of cells occurs via attachment of the virus envelope glycoproteins to cell membrane proteins, and subsequent membrane fusion. You will study this process on un-modified viruses, revealing its real-time dynamics.
Research Environment: You will be exposed to a vibrant multi-disciplinary environment at the physics/life science interface. You will join a well-funded academic team, with an outstanding track record of student supervision and publication output. The supervisory team offers a unique combination of expertise, with strong track records in developing novel optical microscopy techniques applied to life sciences (Langbein, Borri), protein interaction studies and lipid bilayer phase transitions and single molecule methods (Castell), protein synthesis and membrane proteins (Young), and protein design and characterization (Jones).
Training and Development Opportunities: You will be trained in a variety of relevant techniques including optical microscopy, fabrication of synthetic lipid membranes, protein purification. You will develop the transferable skills of data analysis and modelling, communication and dissemination. The resulting skillset will boost your future employability both in academia and in industry. The supervisory team has strong links with companies, including microscope manufactures and image analysis software developers. Within this studentship, opportunities for visits/internships at these companies will arise. Global mobility opportunities will include visiting collaborating partner groups overseas, and participation to national/international conferences. The project will generate new knowledge and data that will be published in high quality journals.
EPSRC funded DTP PhD Studentship within the Interdisciplinary Doctoral Training Hub “Physics of Life”
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.
How to Apply:
Applicants should submit an application for postgraduate study via the Cardiff University webpages (https://www.cardiff.ac.uk/study/postgraduate/research/programmes/programme/physics-and-astronomy
• an upload of your CV
• a personal statement/covering letter
• two references
• Current academic transcripts
Applicants should select Doctor of Philosophy, with a start date of October 2020
In the research proposal section of your application, please specify the project title and supervisors of this project and copy the project description in the text box provided. Candidates should hold a good bachelor’s degree (first or upper second-class honours degree) or a MSc degree in Physics or a related subject. Applicants whose first language is not English will be required to demonstrate proficiency in the English language (IELTS 6.5 or equivalent).