The University of Bath is inviting applications for the following PhD project commencing in October 2022 under the supervision of Dr Nazia Mehrban in the Department of Pharmacy & Pharmacology and Prof Jody Mason in the Department of Biology & Biochemistry.
Biomaterials are used to repair and regenerate tissue and introduce drugs and devices into the human body, in response to specific clinical needs. Upon implantation, they induce an inflammatory response. Ideally, the acute response will promote matrix reconstruction integrating the new material safely with the surrounding healthy tissue. However, a less favourable response may be the development of stable fibres isolating the implant from the rest of the body. This reduces therapeutic efficiency by creating a physical barrier to drug releases and/or cell-guiding chemistries. At one extreme, this could lead to long-term fibrosis and potentially toxic effects such as the induction of amyloidosis,1,2 requiring further unwanted surgical procedures and contributing to patient morbidity and high healthcare-provider costs. At a time when there has never been more interest in the development of smart materials for biomedical applications, including slow-release and soft robotics, such potential adverse responses present a significant, and poorly explored, challenge.
Prevention of the foreign body response that contributes to chronic inflammation, with subsequent fibrosis, is key to designing smart biomaterials. We have designed a peptide-based hydrogel system “bottom-up” by studying nature which allows inclusion of chemistries that are known to guide cell behaviour and promote an anti-inflammatory response once implanted.3-5
In this PhD project, we will study the nature of the foreign-body response to biomaterials and identify short peptide sequences derived from proteins that are known to contribute to the chronic fibrotic process. By understanding the role of these proteins in the formation of a fibrous capsule we will specifically design peptides that prevent the activation of key pathways, thus steering a constructive immune and remodelling response. These peptides will be derived by rational design or using in-cell peptide library screens.6 The peptides will then be synthesised and ‘clicked’ onto the parent peptides that form the hydrogel, providing decoration throughout the biomaterial and crucially at the material-tissue interface. Additional chemistry to promote tissue integration will also be explored, creating dual-purpose functionalised smart biomaterials that trigger a reconstructive response immediately upon implantation and provide tissue-specific key cell-interacting peptidomimetics.
The successful candidate will explore protein design principles and identify key pathways to prevent long-term fibrosis. Once suitable peptides have been identified they will perform screening studies using protein-fragment complementation assays and assess the foreign body response to short derivatives through cell culture, histological studies and protein expression assays. These peptide derivatives will be incorporated into a hydrogel-based material towards avoiding a chronic inflammatory response while ensuring the material integrates with the surrounding healthy tissue and provides reconstruction cues at the injury site. These materials will significantly impact clinical applications that require biomaterial implantation.
Throughout this interdisciplinary project, the candidate will gain specific skills in protein design and manufacture, material characterisation, cell culture and clinically relevant studies.
Project keywords: Peptides; Fibrosis; Biomaterials; Rational Design; Protein Design; Hydrogels; Implantation; Immune Response.
Candidate Requirements:
Applicants should hold, or expect to receive, a First Class or high Upper Second Class UK Honours degree (or equivalent) in a relevant subject such as, though not limited to, biology, biochemistry, biotechnology and chemistry. A master’s level qualification would also be advantageous.
Non-UK applicants must meet our English language entry requirement.
Enquiries and Applications:
Informal enquiries are welcomed and should be directed to Dr Nazia Mehrban.
Formal applications should be made via the University of Bath’s online application form for a PhD in Pharmacy & Pharmacology.
More information about applying for a PhD at Bath may be found on our website.
Funding Eligibility:
To be eligible for funding, you must qualify as a Home student. The eligibility criteria for Home fee status are detailed and too complex to be summarised here in full; however, as a general guide, the following applicants will normally qualify subject to meeting residency requirements: UK nationals (living in the UK or EEA/Switzerland), Irish nationals (living in the UK or EEA/Switzerland), those with Indefinite Leave to Remain and EU nationals with pre-settled or settled status in the UK under the EU Settlement Scheme). This is not intended to be an exhaustive list. Additional information may be found on our fee status guidance webpage, on the GOV.UK website and on the UKCISA website.
Exceptional Overseas students (e.g. with a UK Master’s Distinction or international equivalent and relevant research experience), who are interested in this project, should contact the lead supervisor in the first instance to discuss the possibility of applying for supplementary funding.
Equality, Diversity and Inclusion:
We value a diverse research environment and aim to be an inclusive university, where difference is celebrated and respected. We welcome and encourage applications from under-represented groups.
If you have circumstances that you feel we should be aware of that have affected your educational attainment, then please feel free to tell us about it in your application form. The best way to do this is a short paragraph at the end of your personal statement.
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