BBSRC Innovator of the Year 2014 winners reveal the secrets behind their innovations in a series of three articles.
In this, the second, Commercial winner Dr Curtis Dobson from the University of Manchester explains how work on infections and Alzheimer's disease led to a new class of anti-infective compounds. In the first, Overall Innovator winner Professor Luke Alphey of The Pirbright Institute recalls the ups and downs of his journey to combat dengue fever using genetically modified mosquitoes. And in the third, Most Promising winners Professor Cathie Martin and Dr Eugenio Butelli of the John Innes Centre provide the lowdown on the world of purple tomatoes.
How does it feel to win?
It's obviously fantastic, I didn't really expect to get this far and there was some very strong competition. Everyone here is absolutely delighted – there are lots of other people involved and I'm very happy on behalf of the team.
Can you describe your winning innovation?
It's unusual that two innovations are recognised here. The first, the peptide technology, was essentially making use of a neuroscience research tool that we were using in looking how infection may be involved in pathological events [infections] in Alzheimer's. The tool was a piece of a human protein, a peptide, which was biocompatible but also had a very potent and very powerful anti-infection activity that was safe and effective.
Where could it be used?
We considered therapeutic applications, like as an anti-HIV agent, but they are quite challenging commercially to achieve so we realised there were unmet needs nearer to market, such as medical device infection, where clearly there was a need for better disinfecting compounds.
Why specialise in the medical equipment area?
A lot of the compounds to counter infection in that area have been around for decades and there's certainly a need for improvements. So we began commercialising it as an anti-microbial coating, and some of the people in the team were in the ophthalmic research area. That led to a few years of development projects with companies in the sector and then signing a major deal with Sauflon Pharmaceuticals in 2010.
Did you found a spin-out company to handle the commercialisation?
Yes the company is called Ai2 and I led the company up until that point. Then it seemed a good time to bring in a more experienced management team having established a commercial deal. Products are under development in ophthalmics as well as in other medical devices and wound dressings, and also in in less medical applications such as preservatives, toothpaste and other ways a safe, biocompatible disinfectant can be used.
How did you get from Alzheimer's research to an anti-infection compound?
The link is that I was working on role of anti-infectious agents in Alzheimer's disease (AD). And we found a risk factor for AD, the APOE gene, but it is only a risk factor for patients with herpes simplex virus in their brains. We also found that people with cold sores also tend to have this AD form of the gene, but it's not to say if you suffer from cold sores you'll get AD, it suggests this gene coded for a protein that one way or another interferes or exacerbates with infection.
So my work with the full-length protein coded by the APOE gene led to peptides based on key bits of the protein, which led to other peptides with anti-infective activity against bacteria, viruses and fungi.
Why not use the peptides as anti-infective drugs?
We initially thought that was interesting as therapeutic lead. We first found it had anti-herpes virus activity, and then we found anti-HIV activity, and it worked from a different mechanism to HIV drugs at the time, so this meant this drug could be a fifth way of tackling HIV – blocking attachment of virus to cells. Except it's a very crowded space, and when you try and commercialise you are up against many technologies around the world and a 10-year development timeline at least and you have to raise a lot of money. We didn't give up on that, but at the same time looked around for closer-to-market opportunities.
What was the role of BBSRC funding?
BBSRC came in just around this time. About the time we were talking to contact lens companies we secured a two-year BBSRC SBRI grant and that really transformed things and allowed us to put serious effort into developing the peptides as coatings for medical devices and care solutions.
One of the key innovations then was to modify the peptide sequences so they would stick more readily to different surfaces. The original peptides stuck to certain surfaces, but didn't work with everything, but by modifying it we got it to stick to others polymers and hydrogel surfaces and that really opened up the doors to commercialising seriously – from something that might work to something did work widely.
Did you use other BBSRC funding streams?
We also utilised CASE Studentships to get PhD students in which helped demonstrate the effectiveness of peptides compared to other traditional biocides. A second CASE Studentship looked at the mechanism of action of the peptides, all very important as part of the regulatory process, so BBSRC helped backfill some of the fundamental science while we progressed with the commercialisation.
What's behind the second stream of your innovation?
The idea for the next technology arose when I was out walking the dog in the park, and I was daydreaming about different ways to tackle medical device infection. Rather than kill the bacteria, what if we could signal the presence of colonisation directly and earlier?
Did this come from BBSRC-funded work?
Part of the idea came from some other BBSRC-funded work we were doing visualising bacteria on surfaces. The thinking was that if some of the bacterial indicators we were using could be encapsulated in a structure small enough to be buried in the surface of a medical device it could function as a sterile indicator or infection warning without any operator intervention. Then you wouldn't need a person in a lab coat carrying out tests, it would be automated and passive and when it encountered bacteria it would change colour and indicate that further medical intervention was needed.
What does this look like?
The device, which we call a MicroBiosensor, is about half a centimetre across and you get a deep blue colour change when certain microbiological parameters are met. Beyond 103, 104 colony forming units per square centimetre the colour change will happen – and it's all or nothing so there no mistaking when you shouldn't use the device.
And did you utilise any further grants for this idea?
That was the concept, and we got some proof of principal funding from the University of Manchester in 2011 to get the devices up and running, so that you could challenge with bacteria and the microsensors would change colour. Then we secured a BBSRC Follow-on Fund (FoF) because it had arisen indirectly from a BBSRC project which allowed us to transform a nice idea into something really practical and commercial.
How close is it to market?
We're working on ways to change the indicator thresholds on the device. So in a contact lens case you can make sure it is very sensitive, but in a wound dressing you'd make it a very high number of bacteria to signal an abnormal level. The BBSRC FoF has given us that capability.
What are the main applications of this technology?
The obvious use is an 'intelligent' contact lens case that can tell you when your sterilising contact lens fluid hasn't worked. Around 6000 people lose their vision or visual acuity globally each year from contact lens infection.
Other areas are wound care, general medical equipment monitoring, various procedures in hospital, dialysis and IV lines. We have CDAs in place [confidential disclosure agreements] so I can't say too much. But areas where it's crucial that levels of infection are low.
When might this hit the market?
We have an SBRI grant, basically a UK Department of Health contract, to develop the technology in the renal care area and a Phase 1 six-month project is about to start. If successful, then there is a good chance of securing a further 18-month Phase 2 contract after that, which would take us almost to market.
What did you learn from your first Ai2 venture that you put into the second?
I think there are many ways that fundamental research can be applied, and have uses that you didn't think would be closer to market than you expect. We wouldn't have expected that neuroscience research we were doing would lead to a new disinfectant for contact lenses. If you can develop an awareness of unmet clinical needs, then this can enable you to find surprising ways you can apply curiosity-driven biological research to make products that could be useful to people.
The anti-viral use was the most obvious for the anti-infective peptides at first, but it was not the right answer. Learning from this, enabled us to go ahead with the second project so quickly: I was thinking of the unmet need first and working backwards, thinking laterally, to how unrelated work we were doing in the lab might solve this.
When did you first realise you wanted to be a scientist?
I suppose when I was at school, about the time I was doing 'O' levels. I was always interested in science primarily because of the usefulness of it, rather than just as a puzzle to solve. I'm not saying I don't enjoy that part of it, but I was really driven by the potential science had to change people's lives; other disciplines did not seem to offer that direct connection.
It's fantastic to come up with an idea on a whiteboard and then a few years down the line its being used to benefit millions of people around the world – that's the inspiration.