Materials that can trigger the regrowth and repair of damaged biological tissue have the potential to revolutionise how we treat disease. However, despite the huge promise of the ‘tissue engineering’ field, very few biomaterial-technologies have so far reached patients. This is largely due to difficulties designing materials that can provide cells with the biological signals they need to form new tissue. In this project, we will address this problem by designing new chemical strategies for functionalising biomaterials with potent signalling proteins, called growth factors, used by nature to drive repair.
The difficulty of conjugating growth factors to a biomaterial while retaining high biological activity is one of the major roadblocks to clinical translation. Current strategies typically rely on non-specific chemical modification strategies, usually by targeting abundant amines on the protein surface. This commonly leads to denaturation, blocked active sites, sterically hindered cell-signalling motifs, and ultimately a dramatic loss of protein activity (often > 95 % loss). Here, we will design new growth factor modification chemistries that precisely modify a single amino acid on a protein surface, based on its unique environment. This requires exquisite region-selectivity, enabled by the use of ‘affinity probes’ that generate pseudo-intramolecular environments with high effective molarity, able to drive otherwise unfavourable reactions. By using a modular system to design highly specific probes for a target protein of interest, we will create a powerful platform for protein modification that is universally translatable to any growth factor used in tissue engineering.
During this PhD, we will specifically target growth factors responsible for angiogenesis, the growth of new blood vessels, as initial substrates for biomaterial modification. Without an efficient blood supply new tissue cannot function effectively, and the inability of biomaterials to promote angiogenesis is a major problem in tissue engineering. We will go on to attach our modified growth factors to two classes of clinically-relevant biomaterials, hydrogels and fibrous scaffolds, and investigate their signalling in in vitro models of endothelial cell migration and proliferation.
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, protein engineering, biomaterial synthesis, and mammalian cell biology. 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.
You will join the Molecular Materials Group within the Organic Chemistry Division at York. You will receive training in the key specialities of organic synthesis, chemical biology, and soft material chemistry. In particular, you will receive formal training in solid-phase peptide synthesis, ESI-mass spectrometry, material characterisation techniques, and mammalian cell culture.
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 will formally start on 1 October 2019. Induction activities will begin on 30 September.