Imagine Global Strategic Alliance Scholarship
The Florey Institute and Imagine: Imaging Life are long term strategic initiatives at the University of Sheffield (2022 Futures) that provide a platform for ambitious research growth in areas that the University of Sheffield is recognised for internationally. The Florey Institute aims to create a world-leading focus on antimicrobial resistance and host-pathogen interactions, from fundamental science to translation. Imagine: Imaging Life aims to combine and harness cutting-edge imaging technologies in super-resolution microscopy, electron microscopy and atomic force microscopy to address key biological questions. This scholarship, as part of the Global Strategic Alliance programme, will position the student in a thriving research environment that may provide international opportunities for training and career development.
Project title: Transition-metal based dual optical/electron microscopy imaging probes as new antimicrobial-PDT agents for periodontal disease
Photodynamic (light-activated) therapy (PDT) is an emerging powerful approach to treat illnesses. It uses special drugs which are only toxic when illuminated by visible light, but remain non-toxic without light. This approach presents tremendous opportunities for targeted therapy and dramatically reduce side-effects. So far, the main focus of research in this area was on killing cells – especially cancer cells. This project aims at an even more ambitious target – we want to translate our recent developments in anti-cancer PDT to kill bacteria. Why is it such a challenge? Because bacteria invade the cells, and one must kill bacteria, but not the host cell.
We will focus in particular on the bacterium Prophyromonas gingivalis, which is responsible for tooth loss. We have shown that when this bacterium invades host cells, it is resistant to both therapeutic agents and the immune response. We believe that one alternative to overcome resistance is antimicrobial photodynamic therapy (aPDT) which uses small-molecule light-activated drugs and targeted light applied directly to the gums to activate the drug.
We need the drug which is PDT-active, cell-permeable, and colocalises with the bacteria inside the cells. We have already developed emissive transition-metal complexes (Pt(II),Ir(III)) that are also PDT-active, killing diverse cancer cell-lines (Sci.Reports-2016-22668; Chem.Eur.J.-2016-10.1002/chem.20160479). These compounds will form the basis for our new anitibacterial PDT drugs. They will be modified by targeting side-groups to accumulate specifically in bacteria.
To prove that the drug and bacteria co-localise, we will use emission microscopy and transmission electron microscopy. Once the co-localisation is proven, we will develop illumination conditions to achieve the desired effect – killing bacteria, but not the host cells. Finally, we will attempt a study in a 3D model.
Outcome: The scientific basis for development of a new generation of antimicrobial photodynamic therapy agents.
Skills: The candidate should have a 1st or an upper second class degree in Chemistry, Biochemistry, or equivalent. They should demonstrate a good knowledge of both subjects, and willingness to work with bacterial and cell cultures, light microscopy, electron microscopy, and be able to work in a highly interdisciplinary environment. Depending on applicant’s skills and preference, the project may be more synthesis or more microscopy focused.
Please contact Prof. Julia Weinstein (firstname.lastname@example.org) or Dr Simon Whawell (email@example.com) for more details about the project.
• Full tuition fees (UK, EU or Overseas).
• An annual, tax-free maintenance stipend at the standard RCUK rate.
These scholarships fund up to 3.5 years full-time study, subject to satisfactory progress.
• You should have, or expect to achieve, a first or upper second class UK honours degree or equivalent. This should be in a relevant area (e.g. Biochemistry, Chemistry or related discipline).
• Anticipated start date October 2017
• Awards are open to UK, EU and international applicants.
How to apply
Scholarships are awarded on a competitive basis - applications are assessed on the basis of academic success and qualifications, experience, research background and a clear and well-articulated reason for being considered. For information on applying, please see https://www.sheffield.ac.uk/postgraduate/research/apply/applying