Russell Cox discusses with Nina Notman his fiery introduction to chemistry, his work on polyketide biosynthesis and Bristol's ChemLabS programme                    

Russell Cox is a reader in organic and biological chemistry at the University of Bristol, UK, and a Bristol ChemLabS University Teacher Fellow. He is currently investigating programming in fungal iterative polyketide synthase, by applying molecular genetics, enzymology and synthetic chemistry. Russell is a member of the Natural Product Reports editorial board.

 

 

Who inspired you to become a scientist? 

Two of my uncles moved to the US when I was a young child and they would send me really great presents - chemistry sets, yes, but also kits to make radios, aeroplanes that really flew and robots. When I attended junior school in the New Forest, there was a specialist science teacher - Mr Stevens - who visited on Wednesdays. We did all sorts of science projects such as collecting fungi and flying kites. My best friend at school had a garage stuffed full of old electronic instruments and components, and I vividly remember making simple telephones and connecting early computers together to send messages with wires stuck together with tape! 

Do you remember your first experiment? 

As a young child, while living in Southampton, I remember filling an air-raid shelter in a friend's garden half an inch deep with methylated spirits and setting fire to it [Ed: we don't recommend you try this!]. This was definitely an experiment, but more designed to see whether the friend's mother would notice, or not. She didn't!

Later, in the New Forest, another friend and I dammed up a local stream to try to recreate a scene from The Dam Busters - we flooded a huge area before the dam burst without anyone noticing.

What attracted you to research in biological chemistry?

Being in the right place at the right time. I did a final year research project with Ken Wade during my undergraduate degree at Durham, in the area of inorganic materials. This really switched me on to the possibility of research, but it was a new young lecturer, David O'Hagan, who attracted me towards biological chemistry. I started a PhD with him combining synthesis and fungal biology and was hooked from then. I have always been grateful to have studied chemistry - the ability to synthesise and analyse compounds has underpinned all the advances in my area of research, but the questions of biology remain the biggest. 
 
What are you working on at the moment?

Our biggest project is investigating programming in fungal iterative polyketide synthases. These enzyme systems are responsible for the biosynthesis of a huge range of biologically active compounds. The enzymes responsible are true nano-machines that are programmed to perform a choreographed sequence of reactions. We can change the reactions - but not yet rationally. We are applying molecular genetics, enzymology and synthetic chemistry to investigate this problem. I have great collaborators in Bristol: Tom Simpson in chemistry and Colin Lazarus and Andy Bailey in biology and we have a truly multidisciplinary collaboration. At the moment we are attempting to shuffle genes encoding proteins with closely related programmes in order to dissect the programmes and discover which parts of the proteins are involved.

When was the last time you went into the lab to do an experiment, and what was it?

Last week - I'm developing an experiment for our level II undergraduate labs in which the students set up a computer model of an epoxide opening reaction and examine the transition states for the two regioisomeric possibilities. Later they do the real reaction in the lab and find out whether the modelling got the right answer. I did the reaction to test it out and got a 96% yield! 
I am always tinkering in my lab - we have an aged LCMS system that needs lots of attention and I am the chief engineer. I don't have time to do any proper chemistry now, but the benefit of being a group leader is that there is always something interesting happening in the lab.

What are the wider aims of Bristol's new ChemLabS other than the teaching of the university's undergraduates?

ChemLabS is a truly innovative programme. We were lucky enough to win funding from the Higher Education Funding Council for England to set up a centre of excellence in teaching and learning focussed on practical chemistry. We have invested in our teaching labs to make them world-class, and have brought the level of infrastructure and equipment up to industrial standards. Simultaneously, we have rebuilt all of our practical teaching material and developed a fully integrated digital system (called the Dynamic Laboratory Manual, DLM) to support all of our practical teaching. Students now are encouraged to use simulations of techniques, equipment and individual experiments before they go into the labs. The simulations allow (and encourage) mistakes to be made, as learning from mistakes is a powerful tool. Having used the on-line simulations, students are then prepared to actively learn from their lab experience and make the most of their time in the lab. We now use this methodology at all levels in the School of Chemistry at Bristol, but we are expanding with commercial partners, to make a DLM for AS and A level study. We are also rolling out our ideas to other departments at Bristol in other subject areas, and have plans to introduce post-graduate versions in the near future.

Which historical scientific figure would you most like to have dinner with and why?
 
One of my favourite books as a child was Man Must Measure by Lancelot Hogben. It's a history of mathematics. It still amazes me that Eratosthenes, from Alexandria, calculated the circumference of the Earth using a well, a pillar and sunshine to within 1% of the true value more than 200 years before the birth of Christ. To be able to use abstract mathematics to envisage the Earth as a globe and calculate its size in an age when most people were illiterate and innumerate was a spectacular feat. And I like Mediterranean food!

What advice would you give to a young researcher who wants to forge a career in biological chemistry research?

Move to Germany or the US! The UK has a truly great history of scientific discoveries, especially in biological chemistry, and some great scientists, but we make life difficult for ourselves. Researchers in British universities have to fit research interests in around a full schedule of teaching and administration so time is at a premium, and the funding situation for chemistry is pretty tough in the UK at the moment. At the August EPSRC chemistry panel, just 3 out of 43 grants were funded - a success rate of 7% - that means that 93% of all the grant-writing and refereeing effort was wasted. Grant bodies are increasingly taking money away from responsive mode and spending it in 'priority' areas. If biological chemistry (chemical biology) is a priority area, then fine, but if it's not, then the area will struggle to compete with groups abroad. Groups in the US and Germany have the scale and funding to tackle the really big questions. On the plus side, I do get to work with terrific students from the UK and adversity does tend to breed innovation.

You are a keen and successful teacher of undergraduates (having recently won the Faculty of Science Teaching Prize at Bristol), and were heavily involved in the launch of ChemLabS. What do you view as the necessary ingredients to be a good teacher?

The ability to see problems from different perspectives - our students vary tremendously in their backgrounds and approaches to learning. Being able to find the right approach to help individuals is important. Also having a strong structure in which to embed concepts and skills is important. I am lucky to be working with a very skilled and experienced team at Bristol, and I have learned as much, or more, by being a teacher as any other aspect of my career.

What do you like to do in your spare time?

I've given up setting fire to air-raid shelters, but I still like knocking things down. I am currently working on my house in the Mendips, knocking bits down and building new bits. I recently sawed a huge oak beam out of the loft to create space for a new room, and I enjoy plumbing, wiring and carpentry. I have two young sons and we spend a lot of time together, fishing, sailing and even doing the odd scientific experiment.

Finally, if you weren't a scientist what would you like to be?

I'd be a gardener. Chemistry and gardening have much in common: one has to have a plan and vision and see far ahead. Gardens require patience, nurture and constant attention, and the results are very rewarding - but you don't need to write grant applications!