A 3.5-year dual PhD position is available at the University of Bristol and Macquarie University from January 2023. In this project, we aim to investigate the controlled delivery of artificial anion transporters (anionophores) to epithelial cells using innovative drug delivery platforms. This work is important for the development of channel replacement therapy for the genetic disease cystic fibrosis (CF). Despite the availability of drugs that target the root-cause of CF, not all people with CF benefit from them. There therefore remains an unmet need for innovative CF therapeutics.
In previous work, we have designed, synthesised and tested anionophores, which function as mobile anion carriers that shuttle anions across cell membranes. Through biological testing, we have identified anionophores with promising biological activity, including potency and persistence without toxic effects. However, many anionophores with high activity in artificial lipid membranes are poorly deliverable to cells, arguing that they require specific drug delivery systems to achieve their therapeutic potential. Thus, in this interdisciplinary project, you will develop nanostructured drug-delivery platforms based on mesoporous silica particles to deliver anionophores to CF epithelial cells.
The project brings together a multidisciplinary team of researchers in Bristol (Profs Davis and Sheppard) and Macquarie (Dr Garcia-Bennett). You will receive thorough training in a broad range of state-of-the-art techniques, including small molecule synthesis, drug formulation and delivery, and biological testing. Through the supervisory team, you will access a wide-range of training opportunities to complement project-specific training. On completion of this project, you will be equipped with the skill and expertise for a broad range of life science careers.
The first 21 months of this PhD studentship will be based at the University of Bristol synthesising and testing the biological activity of anionophores, while during the second 21 months at Macquarie University will involve the development and biological testing of nanostructured drug-delivery platforms for anionophores. In Bristol, you will be based with Prof Sheppard’s group in the School of Physiology, Pharmacology and Neuroscience, where you will be part of a dynamic research community investigating ion transport across membranes in different organ systems. However, you will work very closely with Prof Davis’ group in the School of Chemistry, the UK’s number one chemistry department for research. At, Macquarie University, you will be based with Dr Garcia-Bennett’s group in the School of Natural Sciences, which conducts innovative research to find solutions to real-world challenges. Recent publications from Dr Garcia-Bennett, Prof Davis and Prof Sheppard, include Lau M et al. Pharmaceutics. 2022; 14:502; Li H et al. Chem Sci. 2019; 10:9663-9672 and Spooner MJ et al. Chem Sci. 2018; 10:1976-1985.
A first or upper second-class honours degree (or international equivalent) in a biomedical science discipline or chemistry is required for entry to the PhD programme.
The PhD position is available to start in January 2023. Informal enquiries are very welcome and can be sent by e-mail to Prof Sheppard, Prof Davis or Dr Garcia-Bennett. To apply, visit https://www.bristol.ac.uk/study/postgraduate/2022/life-sciences/phd-physiology-pharmacology/.
Closing date: Friday 2nd September 2022