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  Taking Light Induced Electron Paramagnetic Resonance In Cell for Biological Structural Determination


   Department of Chemistry

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  Dr Alice Bowen, Dr Jack Rowbotham, Dr I Riddell, Dr Derren Heyes  Applications accepted all year round  Competition Funded PhD Project (Students Worldwide)

About the Project

Studying the structure of proteins and other biological systems is an important step in understanding their function. Most structural studies are conducted in environments that are far away from native conditions, such as those found inside a cell. This is because native environments are very complex, and it can be difficult to determine which information recorded is from the system of interest and which is from the complex background environment.

Therefore, to measure information on biological systems in-cells it is necessary to use an analytical technique that is both sensitive and specific to the system of interest. One suitable technique is Electron Paramagnetic Resonance (EPR). This is a magnetic resonance method that is used to measure information from systems containing unpaired electrons – interactions between centres containing unpaired electrons separated by 1.5 – 10+ nm can be used to measure the relative positions of these centres yielding structural information on the system to which they belong.

In biological systems centres containing unpaired electrons can be added via site directed mutagenesis and spin-labelling where moieties, often nitroxides are added to the surface of the system. Unfortunately, nitroxides can be degraded in the cellular environment, making them unsuitable for many applications in cells.

In this project we will explore the potential of using light-induced spin centres, based on known chromophores, for making structural measurements on model biological systems in cells. Light will be used to excite electrons in the chromophores – these can then either react to form a stable radical spin centre or intersystem-cross to form a triplet state, which has two unpaired electrons. Triplet state spin labels have the potential to be very well suited to this application as the signal is enhanced by polarization allowing lower concentrations to be used. Additionally, EPR results may be combined with results of other optical

This exciting project build on existing work using model and protein systems in-vitro (Methods in Enzymology, 2022, 666, 171-231) and will involve a combination of EPR spectroscopy, complimentary optical methods such as Fӧrster Resonance Energy Transfer (FRET), data analysis and producing, handling and manipulating biological samples.

We plan on initially introducing model peptide systems into cells using electroporation, and performing optically enhanced EPR measurements on the systems in cells. Once the methods have been established we will aim to apply the same methods to biologically interesting systems including heme-proteins such as P450s.

This project is funded in part by the Royal Society and will involve collaborations with the University of Padova and the Pirbright Institute.

The direction of the project can be driven by the interests of the student appointed and it will suit a student with interests in spectroscopy, analytical and physical methods with a background in Chemistry, Biochemistry or Natural Sciences.

The University of Manchester is a fantastic location for EPR research, with unique state-of-the-art facilities. Within the Photon Science Institute is housed the EPSRC funded National Research Facility for EPR (https://www.chemistry.manchester.ac.uk/epr/), of which Dr Bowen is a member. In addition this project will make use of the biochemical facilities located in the Manchester Institute of Biotechnology (https://www.mib.manchester.ac.uk/)

Information on the supervisory team can be found here:

Dr Alice Bowen: https://research.manchester.ac.uk/en/persons/alice.bowen

Dr Imogen Riddell

https://research.manchester.ac.uk/en/persons/imogen.riddell

Dr Jack Rowbotham

https://research.manchester.ac.uk/en/persons/jack.rowbotham

Dr Derren Heyes

https://research.manchester.ac.uk/en/persons/derren.heyes

The duration of the PhD is 4 years and the start date is 1st October, although candidates may wish to start as early as 18th September to attend the welcome week.

This position will be advertised until the position is filled so please apply at your earliest convenience.

Before you apply

Please contact [Email Address Removed] for informal discussions before you apply with a curriculum vitae.

 Eligibility

Applicants should have, or expect to achieve, at least a 2.1 honours degree or a master’s in a relevant science or engineering related discipline.

How to apply 

To be considered formally for this project you’ll need to complete a formal application through our online application portal.

When applying, you’ll need to specify the full name of this project, the name of your supervisor, details of your previous study, and names and contact details of two referees.

Your application will not be processed without all of the required documents submitted at the time of application, and we cannot accept responsibility for late or missed deadlines. Incomplete applications will not be considered.

If you have any questions about making an application, please contact our admissions team by emailing [Email Address Removed].

For more information, visit our funding page or search our funding database for specific scholarships, studentships and awards you may be eligible for.

Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. We know that diversity strengthens our research community, leading to enhanced research creativity, productivity and quality, and societal and economic impact.

We actively encourage applicants from diverse career paths and backgrounds and from all sections of the community, regardless of age, disability, ethnicity, gender, gender expression, sexual orientation and transgender status.

We also support applications from those returning from a career break or other roles. We consider offering flexible study arrangements (including part-time: 50%, 60% or 80%, depending on the project/funder).

Biological Sciences (4) Chemistry (6)

Funding Notes

This 4 year PhD project is fully funded for UK students with a stipend payable at the UKRI rate. The funding is provided by The Royal Society and The Department of Chemistry.
However, the University of Manchester has a range of additional scholarships, studentships and awards at university, faculty and department level, to support both UK and overseas postgraduate researchers. If you are an overseas student interested in this project or a similar project, please contact [Email Address Removed] for informal discussions about other potential sources of funding.

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