Two new linked projects at the University of Sheffield aim to provide both the technology and the multi-stranded research expertise needed to help address some of the key challenges of infectious diseases.

The Florey Institute for Host-Pathogen Interactions ¨C named after the late Sir Howard Florey, the Sheffield professor of pathology who carried out the first clinical trials of penicillin ¨C now focuses on the devastating impact of two bacteria in particular.

Staphylococcus aureus, notably in its methicillin-resistant form MRSA, is responsible for thousands of community and hospital-acquired infections every year. An even more significant threat, Streptococcus pneumoniae, is the most common cause of pneumonia, which still accounts for millions of deaths worldwide. With growing concerns about the rise of antibiotic-resistant bacteria, new thinking about ways to combat them is urgently required.

The Florey has already drawn on extensive existing expertise within Sheffield. But it ramped things up a gear, even before its formal launch earlier this year, by issuing a call for PhD students to switch to working in this field. It is committed to a multidisciplinary approach, bringing together microbiologists, physical scientists, engineers and mathematicians, and also bridges the gap between academic researchers and clinicians working in Sheffield Teaching Hospitals, incorporating one of the largest regional infectious disease units in the UK.

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Although the researchers are currently distributed across the campus, in the longer term the Florey would like to ¡°put them in contiguous spaces¡±, said co-director David Dockrell, professor of infectious diseases. He also hopes to develop the institute into ¡°a leading international hub¡±, building on a network of universities in Amsterdam, Utrecht, Bonn, Boston and Nebraska that already offer programmes to co-host graduate students.

The Florey has adopted a three-pronged approach to combating infectious diseases. Researchers devote their efforts to finding new (or repurposed) antimicrobials and possible new vaccines; none currently exists for S. aureus. They will also give an unusual degree of attention to the host side, looking at how healthy people generally avoid contracting diseases and how the immune system can be boosted.

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New microscopy tools offer hope

Yet since ¡°our understanding of pathogens and their hosts is to some extent limited by technology¡±, explained Professor Dockrell, this approach also requires the support of the university¡¯s parallel Imagine: Imaging Life project, which also launched this year and ¡°offers the tools to help us ask the next generation of questions¡±.

Imagine¡¯s co-director Simon Foster, professor of molecular microbiology, agreed that recent developments in microscopy provide ¡°about 10-fold better resolution than before¡± and so ¡°open up a whole new realm of biology previously hidden behind the resolution¡±. Separation between cells can now be clearly visualised, rather than guessed at through ¡°a fuzzy penumbra¡±. Interactions can thus be studied at a much finer level of detail, where findings ¡°often don¡¯t match what we¡¯ve been trained to think¡±, Professor Foster said.

So the potential for new insights to feed into the Florey research programme is immense. Yet commercially available systems of super-resolution microscopy are not always well adapted to the specific needs of biologists.

To get around this problem, Imagine has secured funding of more than ?6 million from the Biotechnology and Biological Sciences Research Council, the Medical Research Council, the Wellcome Trust, the Wolfson Foundation and the university itself to purchase cutting-edge equipment, most recently two new super-resolution fluorescent microscopes. These require very careful instalment on bedrock to avoid even the slightest vibrations. More significantly, however, they require a multidisciplinary team to take best advantage of what they have to offer.

¡°The questions are set by biologists,¡± explained Professor Foster, ¡°and they provide the framework for technological development¡±. It is physicists who ¡°adapt and develop the base technologies ¨C they have to be quite bespoke for our needs¡±. Finally, as they begin to observe structures that have never been seen before, ¡°chemists have to create new probes to label them¡±.

The new imaging facilities will enable Sheffield researchers not only ¡°to ask questions we couldn¡¯t ask before¡± but also to set a benchmark for others to emulate, since ¡°now everybody will have to adopt this sort of technology as otherwise they will be using outdated data¡±. With that will come major new opportunities to fight the terrible diseases that cause such immense suffering across the globe.

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matthew.reisz@tesglobal.com