Changing the subject
Scientists today often do research in esoteric areas, but even though this may divide them in terms of their specialist knowledge, they need to work closer and closer together and not just learn new skills but relearn their old subject over and over again – in an environment which also changes year after year...…
The fact he's not a pharmacist may actually have been a big advantage for Professor Graham Coombs in undertaking his role as the head of the School of Pharmacy at the University of Strathclyde. “Instead of training pharmacists for the job as it is,” he explains, “we want them to be able to adapt and ask, what if it changes?”
Coombs, who until April was also head of SIPBS (the Strathclyde Institute of Pharmacy and Biomedical Science), has seen dramatic changes in the course of his own academic career, in terms of scientific knowledge, drug development and the technologies used in research. He has also collaborated with numerous colleagues in the UK and beyond, in academia and industry, and this experience was crucial in preparing him for his role at the Institute, which was formed by the amalgamation of five departments from the Faculty of Science and also works in partnership with some of the biggest names in pharmaceuticals.
SIPBS was founded in 2006 and the idea behind it was simply to make it easier for scientists in different disciplines to work with each other and learn from each other. Its research projects focus on everything from mental health to cancer, and according to Coombs, with the construction of its new building, costing some £36 million, nearing completion, work at the Institute is “coming to fruition” and already making headlines for its breakthroughs in research (see sidebar).
The next generation of pharmacists will therefore emerge from an environment which emphasisesthe importance of multi-disciplinary teamwork and practical research rather than a school which simply teaches them how to dispense a prescription.
As well as being head of SIPBS, Coombs is the Professor of Biochemical Parasitology, and his own research focuses on two unicellular parasitic protozoa –Leishmania, which causes the killer disease leishmaniasis, and Trichomonas, a sexually transmitted pathogen which causes vaginitis and urethritis and may also have a role in HIV transmission. According to Coombs, both these diseases cause widespread suffering and the long-term aim of his work is to “underpin the development of novel therapies, either drugs or vaccines, which exploit unique biochemical aspects of the parasites.”
Coombs developed his interest in parasitic protozoa during his studies at University College London (UCL), and later at the University of Kent, where he did his post-doctoral research on the mode of action of anti-malarial drugs. His general aim was to understand the parasites at the molecular level and “how they are adapted to their environment and live in the host,” which enables biochemists to identify drug targets and develop vaccines.
“I was enthralled with these organisms,” Coombs says, “because they tell us a lot about evolution as well as how they cause diseases.” Studying protozoan cells, he explains, allows you to see the huge differences between them – for example, Leishmania and Trichomonas– and how they have adapted over time in the fight for survival.
Fundamental science is important, says Coombs, but the quest to cure killer infectious diseases continues to drive his research. “I always felt that doing biochemistry had very clear aims,” he adds. “It was not just clever science but had applications.” The international “community” of parasitologists also appealed to Coombs – because there are relatively few of them compared to many other disciplines, it is easier to get to know other parasitologists in countries all over the world and therefore work together beneficially.
Since moving to the University of Glasgow in 1974 to establish his own research group specialising in biochemical parasitology, Coombs has focused on “elucidating biochemical adaptations of a range of parasitic protozoa, including pioneering studies on Leishmaniaamastigotes and peptidases of trypanosomatids,” publishing more than 200 original papers, five books and several patents. In 1986, he was awarded the Seymour H. Hunter prize by the Society of Protozoologists, and in 1993 he was elected as a Fellow of the Royal Society of Edinburgh.
During his career in biochemistry, Coombs has seen dramatic technological advances and the emergence of various trends. There was a time, he says, when biochemical approaches in parasitology “went into a dip” as genetics began to attract greater interest. “The ability to manipulate genes makes it easy to create mutants to investigate the roles of the parasite’s proteins and processes,” Coombs explains, but the focus on genomics can also lead to the neglect of other studies and applications. Whatever is current or “sexy” will always attract lots of funding and followers but the integration of different approaches, and collaboration of biochemists with other scientists with complementary expertise, is the key to long-term progress. In some ways, says Coombs, cloning is actually simple. “I like to do difficult things and take on challenges,” he continues.
In recent years, Coombs has developed an interest in another new technology called metabolomics, using mass spectrometry to produce “super-accurate” measurements of metabolites. For example, to understand the mechanisms used by a parasite like Leishmaniato become resistant to drugs, mass spectrometry techniques are used to study the metabolome– very rapidly and in great detail – of parasites isolated from patients with leishmaniasis. The data generated show the differences between the isolates of drug-resistant parasites compared with drug-sensitive parasites, and this helps to point towards possible cures.
According to a recent paper co-authored by Coombs, “Research at the metabolic level is particularly relevant for parasite biology, where metabolic processes are among the major drug targets. Metabolic biomarkers could ultimately be reliable predictors of treatment outcome... because the concentration of metabolites integrates changes happening at both the genomic and environmental level.”
Metabolomics is playing an increasingly critical role in research, but all these new technologies have key roles to play in the fight against killer diseases. Ultimately, Coombs says, the integration of genomics (the study of genes), proteomics (the study of proteins) and metabolomics (the study of metabolites) will lead to major breakthroughs in research and understanding of pathogens and the development of cures for infectious diseases.
“I'm a great believer in collaboration,” says Coombs, suggesting that all successful research needs the right combination of skills. “We still need broad experience and knowledge – a better understanding of the organisms opens up a better possibility of targeting them with vaccines and drugs.”
Research in biochemistry does not always directly lead to the development of new drugs per se but does provide a better understanding of the mechanisms involved -, which will ultimately lead to new therapies, usually working in collaboration with industry. “There needs to be industry involvement,” Coombs says. “We are primarily doing the science, working at the fundamental level, but we also develop candidate vaccines and diagnostics which industry can then take to fruition of the product.”
Much of the focus of SIPBS is on helping industry improve existing products and discover new ones but Coombs also feels very strongly that the Institute should also help pharmacists prepare to play a new and changing role in society – for example, more clinically focused on patients. “There is also a need for many pharmacists to become involved in research, to provide the evidence base for better use of therapies,” says Coombs. And by creating an environment which brings together different disciplines and is also engaged in internationallyleading research, Coombs hopes the next generation of pharmacists will also be more aware of the need to collaborate – and more aware of the challenges faced by researchers.