A dynamic biomaterial-ligand tethering strategy for tissue engineering

Biomaterials that can trigger the repair of damaged tissues have the potential to revolutionise the way we treat disease. Materials that can present cells and tissues with powerful biochemical signals, through attached peptides, proteins, and carbohydrates, are particularly effective at controlling regeneration. However, despite huge advances in the field we are still unable to design materials that come close to the ‘gold standard’ of healing – the body’s own repair machinery. It therefore remains challenging to translate new biomaterial technologies from the lab to the clinic. The focus of this project will be on how we, as chemists, can take inspiration from nature, to design and synthesise the next-generation of potent biomaterials.
Nature relies on an incredibly dynamic network of interweaved biological signals to drive repair. Different signalling proteins are present in the healing environment at different times, each playing a crucial role in directing regeneration This is in stark contrast to the static triggers currently provided by synthetic materials. This lack of temporal complexity is a major limiting factor in our ability to grow mature and functional tissue. In this project, we will develop new chemistries for the reversible attachment of bioactive peptides and proteins to biomaterial scaffolds. By doing so, we will greatly enhance our ability to create precise and complex signalling cascades in synthetic systems.
During this PhD, we will develop novel conjugation chemistries (‘TAG’) that allow stable attachment of potent signalling peptides, yet can subsequently be released by the application of a biocompatible stimuli (‘TRIGGER’). In doing so, we will regenerate the original reactive handle, allowing us to go through theoretically unlimited cycles of peptide ‘presentation’. This innovative system will allow us to present unique signalling peptides at different stages of tissue growth within a synthetic material for the first time. We will go on to apply our system with collaborators in an in vitro model of cartilage growth for the treatment of osteoarthritis, making use of bioactive peptide sequences that mimic the activity of powerful growth factor signalling proteins to drive tissue maturation.

This highly interdisciplinary project will exploit fundamental principles in organic chemistry to overcome challenges in the field of biomedicine, an example of translational chemical research with a clear pathway to impact in the treatment of disease. Along the way, you will cover aspects of chemical biology, biomaterial synthesis and characterisation, and tissue engineering. You will therefore be exposed to a vibrant research community, focussing on applied research at the interface of chemistry and biology.

All research students follow our innovative Doctoral Training in Chemistry (iDTC): cohort-based training to support the development of scientific, transferable and employability skills. All research students take the core training package which provides both a grounding in the skills required for their research, and transferable skills to enhance employability opportunities following graduation. Core training is progressive and takes place at appropriate points throughout a student’s higher degree programme, with the majority of training taking place in Year 1. In conjunction with the Core training, students, in consultation with their supervisor(s), select training related to the area of their research.

The student will join the Molecular Materials Group within the Organic Chemistry Division at York. They will receive training in the key specialities of organic synthesis, soft material chemistry, and chemical biology. In particular, they will receive formal training in solid-phase peptide synthesis, ESI-mass spectrometry, and material characterisation techniques, along with mammalian cell culture training from project collaborators.

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/. This PhD project is available to study full-time or part-time (50%).

This PhD will formally start on 1 October 2019. Induction activities will start on 30 September.