Investigating Non-thermal ‘Cold’ Plasmas for Enhancing the Delivery and Efficacy of Antibiotics and Complex molecules to biofilms of clinically relevant bacteria

About the project

About the Project Biofilms, complex multi-species consortia of microorganisms existing either as surface attached communities or non-surface-attached aggregates, are characterised by significantly elevated tolerance to antimicrobial challenges and often an inability to adequately treat the infection with conventional antibiotics. Biofilms are implicated in many chronic, recurrent and persistent infections including infections, including those associated with indwelling medical devices and prostheses. Moreover, the diverse nature of the tissues interfacing with the biofilm in vivo complicate bacterial eradication, making current treatments prolonged, expensive and often resulting in significant morbidity, mortality and cost. Such ineffective use of antibiotics also contributes to the evolution of antibiotic resistance. To address this serious issue, this PhD aims to investigate non-thermal, atmospheric pressure plasma, also referred to as ‘cold plasma’ as a novel biofilm control biocidal approach. Non thermal or ‘cold’ plasma is an energised, wholly or partially ionised gas which generates a rich, focally concentrated and diverse mixture of reactive oxygen and nitrogen species which are generated at or near ambient temperatures and pressures. The ability to generate plasma at tissue-tolerable temperatures has given rise to an entire field of research known as Plasma Medicine which aims to translate fundamental cold plasma biophysics to the clinic. The dynamic and diverse array of reactive oxygen species, ROS, and reactive nitrogen species, RNS, generated in a cold plasma have a wide range of biological effects, including antimicrobial activity. In addition, generation of plasma through electrical breakdown of a gas, also gives rise to electric fields which have several biological effects (the ‘bioelectric effect’) including poration of the target cell membrane. Recently, work in our laboratory has shown that short, sub-lethal cold plasma exposures facilitate the delivery of large therapeutic molecules into the biofilm, and across cell membranes, and results in significantly enhanced activity of antibiotics in eradication of biofilms. In the project we will investigate cold plasma exposure as a means to enhance drug delivery both to the biofilm (we have recently shown short cold plasma exposures synergise with antibiotics to eradicate biofilms at low antibiotic concentrations) and intracellularly for the treatment on intracellular infection via a novel process call ‘plasmaporation’. Using multi-omic approaches (transcriptomics, proteomics), cold plasma biophysics and microbiology/biofilm microbiology, this lab-based project will focus on investigating the potential application of cold plasma in antibiotic synergy and in enhancing drug delivery to bacterial and eukaryotic cells. The successful candidate will join a dynamic biofilm research group focused understanding the mechanisms of biofilm formation and antimicrobial tolerance, and developing novel approaches to their detection and control. The project will combine ongoing research into the potential microbiological applications of non-thermal (cold) plasma in delivery of drugs to biofilm and tissue, employing planktonic and biofilm culture models and biofilm antibiotic susceptibility assays alongside molecular biology (PCR, next generation sequencing) and transcriptomics/proteomics. Training that will be provided through the research project You will receive training in culture-dependent microbiology, antimicrobial screening/susceptibility testing , biofilm model development and biofilm antimicrobial susceptibility assays, non-thermal plasma physics, assessment of non thermal plasma for antimicrobial efficacy (including time-kill studies), mechanism of action studies (membrane permeabilisation, polarisation, reactive oxygen and nitrogen species determination), analytical chemistry for drug delivery, and in transcriptomics, proteomics and bioinformatics for identification of cellular targets of cold plasma, cellular response to cold plasma exposure and mechanism of action studies. Oral presentation skills, experimental design and data management, analysis and interpretation are also key skills which will be developed throughout the PhD. Expected impact activities You will join a dynamic, multidisciplinary, output-focused research environment where supporting the development of individuals as critical thinkers is central. As a top-ranked school of pharmacy, the patient is at the centre of what we do. Therefore, it is anticipated that there will be many opportunities for you to demonstrate the impact of your work, primarily through dissemination of your work through publication in leading, peer-reviewed journals and through poster and oral presentations at national and international conferences (typically at least one international conference during your PhD). furthermore, the research group are actively involved in outreach activities, including NI Science Week and visits to/by local schools, as well as engaging with industrial and clinical stakeholders and collaborators. Further funding details Every year the school receives an allocation of funded studentships from the Northern Ireland Department for the Economy (DfE), which can include provision for a small number of fully-funded international studentships. These studentships, which cover tuition fees, stipend and a contribution to running costs, are allocated through a competitive process, with applicants shortlisted and interviewed. All UK applicants will be automatically considered for these studentships and international students with no other funding can request that they be considered for DfE support. However, international DfE studentships are extremely competitive, and applicants should indicate that they wish to be considered for DfE support on their application form. To be eligible for consideration for a DfE Studentship a candidate must satisfy all the eligibility criteria based on nationality, residency, and academic qualifications. The Studentship is open to UK and ROI nationals, and to EU nationals with settled status in the UK, subject to meeting the specific DfE nationality and residency criteria. Full eligibility information can be viewed at: https://www.nidirect.gov.uk/articles/department-economy-postgraduate-studentship-scheme

Research areas