Growth in nanotechnologies can now be exploited to enable engineering of new drug delivery systems for enhancing the entrapment of drugs in nano-sized structures with tailored physical properties to suit therapeutic need. Prof Jian R. Lu’s group has demonstrated that peptide sequences comprising XI4X, where X=K, R, and H can self-assemble into variety of nanostructures including nanotubes and helical nanoribbons. These nanostructures have distinct surfaces with multitude of non-aromatic side chains. Dr Aojula’s group have studied short peptides bearing aromatic drug binding motifs (DBMs) capable of reversibly binding drugs belonging to class of P-glycoprotein (PgP) substrates. These peptides can be further sensitised to penetrate cell membranes. In this project the aim is to engineer new hybrid polypeptide structures by combining the nanostructure forming features of XI4X with drug binding properties of the DBMs to produce novel drug delivery nano assemblies. The specific objectives will be to: a) Design and synthesise hybrid peptide structures, b) MD simulations of side chain and drug binding interactions to predict physicochemical and drug binding properties, c) prepare and characterise nano-assemblies, d) study secondary structures and evaluate drug binding ability, e) study gelation characteristics and formulate into liquid dosage/hydrogels including testing of stiffness and proteolytic stability, f) evaluate drug release profiles under physiological conditions, g) Efficacy testing of the released drug in cell and disease models.
Due to inter-disciplinary nature of the project the student will gain skills across the fields of Chemistry, Pharmaceutical sciences and Biophysics. Peptides will be designed, synthesised, characterised and evaluated for drug binding/kinetics of release and formulated into hydrogels followed by efficacy testing in the Division of Pharmacy and Optometry while the molecular simulations/engineering aspects of nanoassembly and their characterisations will be studied in Biological Physics group in The School of Physics and Astronomy.
Candidates are expected to hold (or be about to obtain) a minimum upper second class honours degree (or equivalent) in a related area/subject. Candidates with previous laboratory experience are particularly encouraged to apply.
How To Apply
For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (https://www.bmh.manchester.ac.uk/study/research/apply/). Informal enquiries may be made directly to the primary supervisor. On the online application form select the appropriate subject title.
For international students, we also offer a unique 4 year PhD programme that gives you the opportunity to undertake an accredited Teaching Certificate whilst carrying out an independent research project across a range of biological, medical and health sciences.
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