Research

Michael Potter

Liposome-based diagnostic and prognostic bio-sensing assay for quantifying the role of sphingomyelinase dysregulation in cardiovascular diseases and depression

Michael Potter - 3rd year PhD

Abstract

Cardiovascular disease (CVD) is the number one killer worldwide, and depression affects one in ten people during their lifetime. Both have been linked recently to abnormal activity of the enzyme sphingomyelinase (SMase) in the body. The ability to measure this abnormal activity would open the door to using SMase as a highly effective biomarker for state-of-the-art diagnostic and prognostic tools, which could significantly improve patient outcome in such diseases. In addition to the huge potential clinical impact, such an assay could also be hugely useful to the pharmaceutical industry for screening new SMase inhibitor drug candidates. However, most laboratory assays rely on hi-tech, multi-step assays or radioisotopes, and there is as yet no successfully exploited, simple clinical test for SMase activity. The aim of this PhD is to develop an innovative technology that will serve as the first-in-field point-of-care device capable of detecting SMase biomarkers.

We propose using liposomes, water-containing vesicles comprising a membrane bilayer of phospholipids, in a state-of-the-art assay using gold nanoparticles, that can be read with the naked eye. Using microfluidic devices, a multi-compartmental liposome that produces different concentrations of hydrogen peroxide in response to changes in SMase activity will be developed. Tiny differences in hydrogen peroxide concentration can be measured using gold nanoparticle growth assays that lead to blue or red solutions.

Led by Prof Molly Stevens, the Stevens Group (2014 European Life Sciences Research Group of the Year) conducts cutting-edge research in multiple areas of regenerative medicine, comprises an exciting multidisciplinary environment and provides an excellent opportunity for training. Dr Oscar Ces and his Group have extensive expertise in lipid phase behaviour, microfluidic strategies for fabricating artificial membranes and membrane-protein interactions. Additional support will be provided by Prof Tony Cass, an innovator in protein engineering and design for new reagents for biosensors and bioanalysis, and Dr Alexander Lyon MD, Senior Lecturer in Cardiology at Imperial and Consultant Cardiologist at the Royal Brompton Hospital, who will provide a library of blood serum samples from CVD patients both with and without depression, with clinical outcome data.