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Light-responsive ‘photoswitches’ for protein chemistry


Department of Chemistry

About the Project

Reversible chemical reactions provide exciting opportunities to functionalise materials and surfaces with proteins and other biomolecules. We are particularly interested in designing new reversible chemistries that can be triggered using light, and in this project we will synthesise novel ‘photoswitches’. These switches will form/cleave covalent bonds under light irradiation in a reversible manner, providing us with a powerful tool for precisely controlling protein conjugation in 3D. By combining our expertise in organic chemistry and chemical biology, we will then explore the applications of this novel approach in the design of materials that promote the growth of complex biological tissues for the treatment of disease.

Objectives:
i) Design, synthesise, and characterise small molecule ‘photoswitches’ that respond to light; ii) Exploit photoswitches to chemically functionalise protein substrates in a reversible manner;
iii) Control the functionalisation and patterning of biomaterials with signalling proteins, with precise 3D control.

Experimental approach:
This highly interdisciplinary project is ideally suited to an applicant with an interest in organic chemistry and chemical biology. A major focus of the project will be on designing and synthesising novel small molecules and then applying them in bioconjugation reactions, before moving into the synthesis of new biomaterials later in the project.
The project will begin with the synthesis of small molecule model systems that we can use to optimise our photoswitchable chemistry. We will use a combination of modelling and experimental data to design new scaffolds for synthesis, and then characterise the photophysical properties of the molecules that we make.
We will then go on to functionalise model proteins with photoswitchable fluorophores, allowing us to study the reversible attachment of small molecules to these biomolecules via a combination of mass spectrometry and fluorescent studies.
Finally, we will use our developed new chemistries to attach potent signalling molecules to hydrogel materials in a patterned and reversible way. This will allow us to control the attachment, growth, and behaviour of cells with 3D control. This will be studied via a range of microscopic and molecular biology techniques.

Novelty:
At present, all photoswitchable reactions are limited by a reliance on changes in conformation and non-covalent interactions to provide reversibility. There are currently no examples of truly reversible photoswitches that both modulate covalent linkages and are applicable to the modification of sensitive biomolecules. This is a major limitation in the development of light-responsive materials and bioconjugates. This project will therefore provide a major innovation in chemical biology with exciting applications in medicine and biotechnology.

Training:
The highly interdisciplinary nature of this project will provide applicants with a broad range of skills across applied and translational chemistry, placing them in an ideal position for a future career in the biomedical sciences. The student will join both the Molecular Materials and Chemical Biology Groups at York, which bring together expertise in the chemical design of materials and bioconjugates for next-generation technologies. The student will receive specific training in advanced organic synthesis, peptide and protein chemistry, and biomaterials science from the Spicer Group, and will be further trained in DFT and modelling in the Lynam Group.

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/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/.

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/

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


Funding Notes

This project is available to students from any country who can fund their own studies.

The Department of Chemistry at the University of York is pleased to offer Wild Fund Scholarships. Applications are welcomed from those who meet the PhD entry criteria from any country outside the UK. Scholarships will be awarded on supervisor support, academic merit, country of origin, expressed financial need and departmental strategy. For further details and deadlines, please see our website: View Website

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