Case study

Morgan Alexander and Paul WilliamsProfessor of Biomedical Surfaces and Director of EPSRC Programme Grant in Next Generation Biomaterials Discovery, University of Nottingham (Morgan Alexander) Professor of Molecular Microbiology, University of Nottingham (Paul Williams)            Investigator Awards in Science

Getting Wellcome Trust funding

What attracted you to Wellcome and to this scheme?

Morgan Alexander

Morgan: Martyn Davies and I had introduced a high-throughput materials discovery platform, originally developed by Robert Langer and Dan Anderson at Massachusetts Institute of Technology (MIT). We could look at how cells interacted with 1,700 different polymers on a single slide and understand the role of the material surface.

We’d identified materials supporting the growth of stem cells and wanted to start looking at inhibiting the growth of microbes on surfaces, given its importance in medicine and other fields. So we needed a microbiologist – and fortunately Martyn knew Paul. A PhD student showed that the platform worked with bacteria.

Someone from the Wellcome Trust saw his poster and suggested we apply for a Translation Award. The three of us applied and got £1.3m. One of our polymers is now being used in the development of a new urinary catheter.

Paul: Although we had an effective product, we’d arrived at the answer empirically – we didn’t know how it actually worked. Wellcome suggested we apply for an Investigator Award to look at mechanisms – a bit like ‘reverse translation’. If we could discover the mechanisms, we might be able to improve materials or develop alternative ways to prevent attachment.

Morgan: A nice thing about the Investigator Award was that it allowed us to ask big questions without having a lot of supporting data. We just had these very interesting materials and some ideas about how they might work. As well as the core idea, the Trust’s interested in whether you have the track record and skills to deliver what you’re proposing.

What aspects of the Joint Investigator Award funding are most useful to you?

Paul: It has enabled us to develop a genuinely interdisciplinary programme. We’re taking advantage of Morgan’s links to the National Physical Laboratory and planning to use new technologies they’re developing. We’re also using the latest imaging and genetic technologies to examine how bacteria respond to encounters with new materials. We have joint meetings and our students spend time in both labs. Also, the main new bit of kit Morgan needed has ended up in my lab as it needed to be in containment facilities.

It is a truly integrated programme. I’m not sure other funders would have supported such an equal partnership.

What do you think of the application process?

Morgan: The Joint Investigator Award started with a long phone conversation with the Trust. I think they liked the idea, but weren’t sure if it was the kind of thing they funded. The medical benefits were obvious to me, but the way I was describing the work just didn’t sound right. Then they said, ‘Do you know there are Joint Investigator Awards?’ I didn’t. With Paul as a joint applicant rather than collaborator, the biomedical relevance of the proposal could be made much more obvious.

Paul: We had to do a double act for the interview. But we still only had three slides and ten minutes to convince the panel that we were worthy of funding. I think we spent more time on the presentation than the proposal. We must have done it seven times, in front of colleagues. We were hopeless to begin with, but we honed our act until we both got our respective points across.

Morgan: Because there were two of us, we pushed each other on to make sure we were on the money. I think we both felt it was the best presentation we’d done.

How challenging have you found it to secure funding?

Morgan: Our initial translation proposal got turned down by another funding agency. We developed our thinking a bit, and ended up getting substantially more from the Wellcome Translation Award. And we delivered on that. 

I had a £1m proposal turned down by the Engineering and Physical Sciences Research Council (EPSRC). I thought about that and went back with a bid for £7.7m – which I got. So, if at first you don’t succeed, go back with a more compelling project, which may be for more money.

What advice would you give to other applicants?

Paul: Get colleagues outside your field to read your proposal. Make sure the importance of what you’re proposing comes across. Referees will be experts but panel members are generalists – they need to ‘get it’ straightaway.

Morgan: If you’re coming from the physical sciences, you’ve got to make allowances for the differences between disciplines. Concepts of excellence differ and publications will be unfamiliar. You’ve got to go out of your way to explain yourself in a way that will make sense to someone from a biomedical field.

Paul: For joint awards, you’ve got to make sure you’ve got the balance right. It must be a genuine mutually dependent partnership and a partnership of equals. You both need to be leaders in your respective fields. Getting the costing right is also important. The Trust is generous, but if you over-cost you’ll be found out and if you under-cost you won’t look credible. Think big, but justify rigorously what you’re asking for.

Morgan: Think about getting your host institution to chip in. During institutional review of our application, we persuaded the university to commit additional PhD studentships. It’s a sign your host institution truly believes in you.

Career path

Career summaries

Morgan Alexander

  • 2014 Senior Investigator Joint Award
  • 2004–present Professor of Biomedical Surfaces, Nottingham
  • 1998–2003 EPSRC Advanced Research Fellow/Senior Lecturer (UMIST)
  • 1996–98 Marie Curie Fellowship, Lyon, France
  • 1993–96 Postdoc, Sheffield
  • 1992–93 Surface Analytical Consultant, Manchester
  • 1992 PhD in surface chemistry, Sheffield

Paul Williams

  • 2014 Senior Investigator Joint Award
  • 2008–13 Head of School of Molecular Medical Sciences, University of Nottingham
  • 1996–2008 Director, Institute of Infection, Immunity and Inflammation, University of Nottingham
  • 1996 Promoted to Professor (University of Nottingham)
  • 1993 Promoted to Reader (University of Nottingham)
  • 1985–93 Lecturer in Pharmaceutical Biochemistry, University of Nottingham
  • 1984–85 Postdoctoral fellow, University of Aston
  • 1984 PhD in microbiology, University of Aston
  • 1979-1980 Pre-registration Pharmacist, City Hospital, Nottingham

What have been the defining moments in your career so far?

Morgan: I always wanted to work on biomaterials, but I kept being successful in engineering-related applications and unsuccessful in biologically related ones. I needed someone to take a chance on me – and that’s what Martyn Davies did. That was my big break. It was a sideways move at the time but it’s worked out fantastically well.

Paul: Back in the 1990s, I was using genetics to investigate antibiotic biosynthesis pathways in soil bacteria. We were convinced we’d identified key steps in a pathway leading to carbapenems. But what we found was that individual bacteria were talking to one another1. This was an early example of what became known as ‘quorum sensing’ – a paradigm shift in thinking about how bacteria in populations interact. Most of my career has been based on this discovery. 

The other key factor was Martyn Davies – he was the one who brought us together.

Research and public engagement

What’s the key question you’re addressing?

We want to understand two things. First, what makes our polymer surfaces so repellent to bacteria. And second, the molecular mechanisms by which individual cells and bacterial populations collectively sense and respond to such surfaces.  Our ultimate aim is to understand the key key properties of our materials that make them repellent to bacteria. This would help us to refine our materials so they’ are even less friendly to bacteria

How are you going about answering this question?

We’re using advanced imaging technologies to visualise how bacterial cells approach and interact with surfaces. And we’re using sophisticated surface chemistry techniques to explore the ‘footprint’ left by bacteria. From the bacterial perspective, we’re using genetic approaches to identify the key sensing and signalling pathways controlling how cells respond to surfaces. We’re concentrating on Pseudomonas aeruginosa, which is notorious for sticking to surfaces. It persists in healthcare facilities, periodically sparking new outbreaks.

What public engagement or outreach work do you do?

Morgan: Through the Training Partnership, I gave two lectures to 950 GCSE students at UCL to show them some of the possible applications of chemistry. It was great fun.

Paul: We’ve done a lot, including Cafés Scientifique, radio programmes and Mayfest, the university’s annual ‘open house’. We’re also hoping to be involved in a Royal Society Summer Exhibition.

References

  1. Jones S et al. The lux autoinducer regulates the production of exoenzyme virulence determinants in Erwinia carotovora and Pseudomonas aeruginosa. EMBO J 1993;12(6):2477–82.
  2. Celiz AD et al. Materials for stem cell factories of the future. Nat Mater 2014;13(6):570–9.
  3. Hook AL et al. Combinatorial discovery of polymers resistant to bacterial attachment. Nat Biotechnol 2012;30(9):868–75.

More information;

Find out more about Paul on the University of Nottingham website.

Find out more about Morgan on the University of Nottingham website or follow him on Twitter.

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