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An interview with Professor John McGeehan

Gribbles

Professor John McGeehan
(Credit: University of Portsmouth)

Professor John McGeehan is Director of the Institute of Biological and Biomedical Sciences at Portsmouth (IBBS). He’s been involved in ground-breaking research involving enzymes and their use to degrade plastic waste made from Polyethylene terephthalate (PET) and the breaking down of waste products to provide building blocks for sustainable materials, a story that made the headlines in early 2018.

John and the team at IBBS have received funding from various UK Research and Innovation councils, including BBSRC. John and his team have shown how successful cross-council research funding can be. Here, we ask him about his important work.

Can you explain what your research is about?

I currently lead the Centre for Enzyme Innovation (CEI) at Portsmouth University which targets major global challenges including the development of solutions for plastic pollution, and clean growth for sustainable chemicals, materials and biofuels. We have a focus on the discovery, characterisation and development of natural enzyme systems, and through understanding the mechanisms of these powerful and selective biological catalysts, we are engineering their activities towards practical applications.

I believe we are just scratching the surface of what can be achieved with enzymes. In relation to plastics for example, while we are making progress we need to explore biological chemistries that can tackle the wide variety of plastics that are polluting our environment.

Professor John McGeehan

What drives you in your research and quest for answers?

I am passionate about molecular biology and I am constantly amazed by the diversity and innovation that can be found in nature. Most of the chemistry of life centres around key reactions that are facilitated by enzymes, so for me this is such an exciting space to be working in. As Director of the Institute of Biological and Biomedical Sciences at Portsmouth (IBBS), I get to see the wide roles that enzymes play in everything from the environment to human health and wellbeing. A major personal driving force is the benefits that a detailed and fundamental molecular understanding of enzymes can provide to the wider scientific community, no matter what the discipline. I feel incredibly fortunate to have access, not only to our extensive in-house biophysical equipment but also to the world-leading expertise available on our doorsteps such as the Diamond Light Source and the Research Complex at Harwell. The wealth of instrumentation provides incredible state-of-the-art research possibilities, but my inspiration always comes from the brilliant researchers that I meet.

Could enzyme science be used to deal with environmental issues?

I believe we are just scratching the surface of what can be achieved with enzymes. In relation to plastics for example, while we are making progress on the depolymerisation of aromatic polyesters such as PET and PEF, we need to explore biological chemistries that can tackle the wide variety of plastics that are polluting our environment. This will involve searching in extreme and unusual environments and a great deal of innovation will be required to find, characterise and deploy these ‘yet to be found’ activities. In parallel, our most abundant polymers; cellulose, lignin and chitin, have the capacity to provide us with long-term building blocks to generate sustainable materials that can feed a circular economy globally, reducing our carbon footprint, and mitigating the consequences of our impact on climate change. I see a very promising future for biological enzymes, particularly when coupled and integrated with chemical catalysis to upcycle monomers to materials with enhanced properties.

What about international collaboration?

Our main international collaborators are in the USA, although we also have strong networks in Europe. We have a highly productive collaboration with the National Renewable Energy Laboratory (NREL) in Golden, Colorado. Following an introduction to Dr Gregg Beckham by Prof. Mike Himmel in 2012, I have worked with many members of their team. Gregg, an inspiring young scientist with a large team of researchers and a recently awarded UK Royal Society Beilby Medal in his pocket, has co-authored and led some of my favourite papers on enzyme research. Indeed, US research in general in this area has always been strong, exemplified with Frances Arnold receiving a share in the 2018 Nobel Prize for Chemistry on ‘the directed evolution of enzymes.’ It is therefore reassuring that the UKRI are continuing to support such joint-funded international opportunities.

Is this collaboration part of an internationally funded consortium?

We are fortunate to have a wide network of superb international collaborators, some of which were formed based on BBSRC-funded partnering awards. These networks are clearly evidenced in our latest publication on plastic digesting enzymes with 21 authors from 5 institutions, and on lignin-active enzymes, with 14 authors from 7 institutions. These large teams from multiple UK, US and Brazilian groups worked together, in what is for me, an exciting multi-disciplinary approach. I currently lead the UK part of a BBSRC-NSF grant, while my colleague Prof. Ellen Neidle leads the US component. This grant, which funds my group, 3 US groups, and also supports our partnership with NREL, has allowed us to explore the enzyme pipeline, from fundamental discovery, molecular characterisation and simulation, through to the development of novel bacterial strains utilising our engineered enzymes and pathways.

Which projects have BBSRC been involved in funding ?

My initial work on DNA binding and modifying enzymes, led by Prof. Geoff Kneale, was my introduction to BBSRC responsive mode funding and continued support allowed us to produce 25 joint papers. Subsequently, working with Prof. Simon Cragg at Portsmouth, and colleagues at the University of York, we had a BBSRC partnering award and two successive sLoLa grants allowing us to explore the natural diversity of lignocellulose enzymes found in woodboring organisms. More recent BBSRC-NSF joint funding has enabled the development of new enzymes targeted towards valorising lignin and also the characterisation and engineering of the PETase plastic-degrading enzyme . My colleague Prof. Anastasia Callaghan has a strong track record in BBSRC funding and has recently been awarded funds to progress her RNA array systems, a technology which we are now integrating into  our enzyme research within the CEI. We have also made productive use of the BBSRC networks, particularly LBNet and P2PNet, which I am delighted to see reincarnated for the next 5 years in the newly developed NIBB Phase II. Utilizing the BBSRC Business Interaction Voucher scheme was instrumental in striking up a productive collaboration with Novozymes on challenging marine enzyme production and these networks have really facilitated great interactions.

Gribbles

Portsmouth PhD research students Tom Shakespeare and Harry Austin receive the first enzyme preparations from GlaxoSmithKline
(Credit: University of Portsmouth)

Have any projects gone forward to feed into commercial methods?

Following the publication of our PET degrading enzyme paper, and publicity reaching an audience of over 200 million, we received wide-ranging commercial interest. I am particularly excited about the commercialisation opportunities after being approached by Ted Chapman and Ben Huckle at GlaxoSmithKline, who invited us to their impressive Biotechnology and Environmental Shared Services facility in Worthing, not far along the coast from Portsmouth. With a suite of 100-4,000 litre fermenters and extensive downstream processing capabilities, we are excited to be doing initial trials with them on the production of our engineered PET-digesting enzymes. Success here opens possibilities to work with companies to develop recycling solutions that integrate biological catalysts. Our collaboration with GSK has already reduced the timeline towards enzyme production at scale, but significantly, I believe that working with industry at the earliest stages of development will allow us to target relevant enzymes for relevant processes. We have several recent patents on engineered versions of enzymes that are active on plastics and lignin polymers, and Prof. Callaghan is making significant progress in the commercialisation of her array technologies.

 

How is the UK placed in the field of enzyme research?

The UK has always punched above our weight in terms of our international research outputs with respect to the percentage of GDP we rely on for funding, and I am happy to report that enzyme research is no exception. While my own focus is driven toward environmental aspects, I have also published with my wife, Dr Rhiannon McGeehan, who leads a group targeting enzymes for mitochondrial disorders and brain tumours. Targeting the medical aspects of enzymes is another area of significant growth in the UK research base. The UK scientific community continues to lead in the publication of fundamental and high-impact research in these areas, but we need to be aware that the competition is strong and growing. In order to maintain our lead, we need continued investment in fundamental research and I am hopeful that the creation of UKRI will generate more synergistic routes to the timely commercialisation of these discoveries.

Do you work with any of the other research councils?

Our Institute (IBBS) spans the majority of these research councils and we attract BBSRC, EPSRC, MRC and NERC funding. My own research team has been generously funded by the BBSRC and we make extensive use of STFC funded infrastructure. We are currently developing substantial bids for Research England, EPSRC and Innovate UK.

Tell us one unusual thing about you we wouldn’t expect?

When I first became a Professor, I made the decision to be open about mental health, and at my inaugural lecture, revealed my struggles with depression over the years. With my enthusiastic and generally smiley demeanour, it did surprise many of my colleagues, but of course, those who suffer from depression will be quite aware of the façade that we often hide behind. I am encouraged that mental health awareness is increasing for our students and staff at UK universities and research institutes. I have come across many exceptional scientists who have chosen to hide their battle with depression. Personally, I find the ability to be open and transparent a huge help, but it is not a route for everyone. Thus, I strive for the day when all stigma is removed from mental health and those that suffer, some of our most precious people and some of our most creative scientists, receive the understanding and support they deserve.