Severe tissue damage underlies many of the leading causes of death and morbidity worldwide. In this project, we will develop new bioconjugation chemistries that allow the synthesis of materials able to harness nature’s own repair mechanisms to address this damage. By exploiting our expertise in organic synthesis and chemical biology, we will specifically develop materials that aim to repair the cartilage damage present in patients suffering from osteoarthritis. By achieving highly controlled and selective enrichment of pro-regenerative proteins released by cells, this highly interdisciplinary project will therefore produce a potential system to address the debilitating symptoms of this devastating disease, as well as a general design platform to address the damage of other tissues in the human body.
Objectives:
i) Design orthogonal bioconjugation strategies for biomaterial functionalisation;
ii) Produce biomaterials able to selectively enrich pro-regenerative growth factor proteins;
iii) Demonstrate enhanced cartilage development in in vitro models of osteoarthritis.
Experimental approach:
This highly interdisciplinary project is ideally suited to an applicant with an interest in organic chemistry and chemical biology.
The major focus of Years 1-2 of the project will be on the design and synthesis of novel reagents for orthogonal bioconjugation. This will entail chemical and peptide synthesis, as well as protein modification. A combination of NMR and mass spectrometry studies will be used to assess reaction efficiency and selectivity.
The project will then move towards the chemical modification of protein-based hydrogel biomaterials in Years 2-3. This will exploit techniques in recombinant protein expression, bioconjugation, and material synthesis and analysis, including growth factor-binding studies and rheological analysis of mechanical properties.
In the final year of the project, we will then exploit the developed materials to direct the behaviour of human mesenchymal stem cells in in vitro studies of chondrogenesis (cartilage growth). The student will be fully trained in the mammalian cell culture, microscopy, and molecular biology techniques required to analyse stem cell fate and tissue development.
Novelty:
Nature relies on the selective enrichment of cell-secreted proteins that serve to amplify cell growth and development for tissue repair. Though biomaterials able to modulate cell behaviour promise to revolutionise the treatment of disease, an inability to recreate these complex signalling cascades leads to tissues that are too immature to successfully treat disease.
This project aims to address this problem by developing novel materials that can control the enrichment of multiple cell-signalling proteins in parallel for the first time. The development of new bioconjugation strategies that can be applied in an orthogonal manner are essential to achieve this goal. By focussing on the design of a highly modular and innovative biomaterial platform, we will ensure the technologies developed can be readily applied to the growth and development of many tissues, and therefore the treatment of a wide-range of diseases in the future.
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. As part of the group of Dr Chris Spicer, the student will join both the Molecular Materials and Chemical Biology Groups at York, which bring together leading expertise in the chemical design of new bioconjugation strategies and biomaterial preparation. Students will be trained in these critical aspects of the project within the Spicer Lab. The student will also join the group of Prof. Paul Genever, an expert in the regeneration of osteochondral tissues. There, the student will be trained in all aspects of mammalian cell culture and stem cell molecular biology.
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/.
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 2021. Induction activities will start on 27 September.
To apply for this project, submit an online PhD in Chemistry application: https://www.york.ac.uk/study/postgraduate/courses/apply?course=DRPCHESCHE3
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