Development and mechanistic characterisation of membrane-active anticancer peptides

Organisms are well known to produce their own antibiotic host-defence peptides that act through damaging bacterial membranes due to their different molecular composition compared to the host organism’s own cells. Some of these antimicrobial peptides are also known to have anticancer properties. One particularly promising anticancer peptide is polybia MP1 (MP1) from the venom of the Brazilian wasp Paulista Polybia. MP1 is more potent at disrupting membranes with increased compositions of aminophospholipids (PE, PS), lipids that are known to be more abundant in many cancer cell types. Towards our long-term goal of realising a new class of anticancer therapies based on membrane-active peptides, we aim to understand the structure-function relationship of a family of designed peptides based on MP1. We will achieve this by detailed mechanistic characterisation in systems of increasing complexity from model membranes to cell culture to provide unprecedented and exquisite insights into the relationship between the peptides’ chemical structure, its biophysical and biological properties and their dependencies on the precise lipid composition of the membrane. This interdisciplinary project will investigate targeted modifications of the MP1 structure to optimise the potency and selectivity of this peptide with a view towards preclinical testing and robust evaluation of the therapeutic potential of this approach. Supervised by Dr Paul Beales (chemistry) and Dr Thomas Hughes (medicine), you will conduct biophysical and biological studies to underpin the mechanistic properties of some of our MP1-derived peptides.

This PhD project aligns with a recently awarded 42 month EPSRC Healthcare Technologies grant. You will be engaged within a larger multidisciplinary team, including two dedicated postdoctoral researchers and additional collaborators and project partners in physics at Leeds and in Sao Paulo, Brazil, as well as lipidomics in Durham and electrophysiology in York. This will provide broad opportunities for you to train and develop your skills as an interdisciplinary research scientist. The PhD project will start on 1st April 2019. An earlier start date may be possible in discussion with the project supervisors. Interested candidates should contact Dr Beales ([email protected]) or Dr Hughes ([email protected]).