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A Chemical Biology Synthetic Toolkit to Covalently Attach Proteins to Surfaces


   Department of Chemistry

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  Dr A Parkin  No more applications being accepted  Funded PhD Project (UK Students Only)

About the Project

Background

As part of the £1.7mill project, “Modernising electrochemical enzymology to map electron transfer” this PhD Studentship will deliver new methodologies to “wire” enzymes to electrodes, utilising cutting-edge chemical biology methods in linker molecules which covalently electro-graft enzymes onto a wide variety of materials. This innovation will have application in biotechnology since devices such as medical sensing devices, enzyme reactors, fuel cells and tissue engineering platforms require the generation of stable protein/enzyme modified surfaces. The legacy of this project, the powerful toolkit of methodologies which we deliver, will be used by us and others as the platform for definitively mapping the redox reactivity of advanced biofuel enzymes, and also probing mechanisms of biological electron transfer in protein-folding, DNA regulation and drug metabolism, all essential cellular processes.

Objectives

The aim of this project is to develop synthetic routes to bi-functionalised linker molecules that contain “headgroups” for site-selective cross-linking to protein molecules, and “tail groups” for light-activated electro-grafting onto conducting surfaces. The powerful utility of these linker molecules in biotechnology applications will be showcased via the immobilisation of hydrogen-producing metalloenzymes for light-driven water-splitting, and extension into bio-medical and bio-synthetic devices.

Experimental Approach

The proposed linker methodology builds on the Parkin group’s experience in biomolecule-electrode immobilisation.1-5 The project will utilise small molecule organic synthesis, molecular biology methods for installing amino acids into proteins, mass spec and protein electrochemistry.

Novelty

By generating methods to “print” proteins onto silicon surfaces and site-selectively “wire” complex metalloproteins on electrodes you will be able to make new biotechnology devices and also gain new electrochemical insight into the fundamental mechanisms via which Nature achieves highly active, efficient, and selective biofuel transformations at non-precious metal enzyme active sites. The work therefore has fundamental importance in developing low carbon energy technology and understanding how to develop new protein technologies.

Training

This PhD project will be carried out in close collaboration with a postdoctoral researcher who will develop a complementary family of linker molecules to test for creating light-patterned biotechnology devices. Training will be provided in all aspects of the work. The Parkin group forms part of the Chemical Biology sub-group of the York Structural Biology Laboratory. We therefore have access to a suite of interdisciplinary chemical, biochemical, microbiology and molecular biology lab spaces, all fully equipped and supported by a phenomenal lab technician. You will be joining a thriving and growing team.

All Chemistry research students have access to our innovative Doctoral Training in Chemistry (iDTC): cohort-based training to support the development of scientific, transferable and employability skills: https://www.york.ac.uk/chemistry/postgraduate/training/idtc/

The Department of Chemistry holds an Athena SWAN Gold Award and is committed to supporting equality and diversity for all staff and students. The Department strives to provide a working environment which allows all staff and students to contribute fully, to flourish, and to excel: https://www.york.ac.uk/chemistry/ed/. 

For more information about the project, click on the supervisor's name above to email the supervisor. For more information about the application process or funding, please click on email institution

This PhD will formally start on 1 October 2023. Induction activities may start a few days earlier.

To apply for this project, submit an online PhD in Chemistry application: https://www.york.ac.uk/study/postgraduate/courses/apply?course=DRPCHESCHE3

You should hold or expect to achieve the equivalent of at least a UK upper second class degree in Chemistry or a related subject.  Please check the entry requirements for your country: https://www.york.ac.uk/study/international/your-country/


Funding Notes

Value: Studentships are fully funded for 3.5 years by a European Research Council grant (funded through the UKRI Frontier Research Guarantee) and cover: (i) a tax-free annual stipend (£17,668 2022/23), (ii) tuition fees at the home rate, (iii) funding for consumables.
Selection process:
You should hold or expect to receive at least an upper second class degree in chemistry or a chemical sciences related subject
Applicants should submit a PhD application to the University of York by 7th January 2023.
Supervisors may contact candidates either by email, telephone or web-chat
Candidates will be notified of the outcome of the decision by email

References

1. Suravaram, S. K.; Smith, D. K.; Parkin, A.; Chechik, V., Conductive Gels Based on Modified Agarose Embedded with Gold Nanoparticles and their Application as a Conducting Support for Shewanella Oneidensis MR-1. ChemElectroChem 2019, 6 (23), 5876-5879.
2. Yates, N. D. J.; Fascione, M. A.; Parkin, A., Methodologies for “Wiring” Redox Proteins/Enzymes to Electrode Surfaces. Chemistry – A European Journal 2018, 24 (47), 12164-12182.
3. Wait, A. F.; Parkin, A.; Morley, G. M.; dos Santos, L.; Armstrong, F. A., Characteristics of Enzyme-Based Hydrogen Fuel Cells Using an Oxygen-Tolerant Hydrogenase as the Anodic Catalyst. The Journal of Physical Chemistry C 2010, 114 (27), 12003-12009.
4. Yates, N. D.; Dowsett, M. R.; Bentley, P.; Dickenson-Fogg, J. A.; Pratt, A.; Blanford, C. F.; Fascione, M. A.; Parkin, A., Aldehyde-Mediated Protein-to-Surface Tethering via Controlled Diazonium Electrode Functionalization Using Protected Hydroxylamines. Langmuir 2020, 36 (20), 5654-5664.
5. Juan-Colás, J.; Parkin, A.; Dunn, K. E.; Scullion, M. G.; Krauss, T. F.; Johnson, S. D., The electrophotonic silicon biosensor. Nature Communications 2016, 7 (1), 12769.

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