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Researcher Spotlight: Professor Mike Barrett

8 Sep, 2014

Professor Michael BarrettMike Barrett is Professor of Biochemical Parasitology and Director of Glasgow Polyomics and a member of the Wellcome Trust Centre for Molecular Parasitology at the University of Glasgow. His work involves interpretation of enormous datasets, with a core focus on drug action and resistance in protozoa. We asked Michael to explain his work and share some of the highlights of his career…

What are you working on?

My core research revolves around identifying how protozoa become resistant to drugs and how drugs work.

This work lead to me founding “Glasgow Polyomics”, where we use state of the art technology to collect data on genomes, proteomes and metabolomes. We do this in an informatics-rich environment, enabling us to optimise interpretation of these huge datasets.

Genomics is the best known of these technologies – most people are familiar with the fact we can now systematically generate sequence information on whole genomes relatively easily. Proteomics looks at all of the proteins in a given system and metabolomics quantifies the small chemical building blocks from which everything is built. We really can dissect life down to its constituent pieces. The great strides in reductionist biology are more or less complete.

The challenge, however, has been to understand how these component pieces fit together to create “life”, which is very much more than the interaction of numerous inanimate chemicals. We now apply polyomics at every level of biological research. I am fortunate in having two fantastic teams in parasitology and in polyomics, teams of people with absolute dedication and amazing skills sets.

What does your average day involve?

As I’m split across two campuses, one where my parasitolgy research team works, the other where Glasgow Polyomics resides, I carry my time between sites. Mornings are usually spent strategically planning research at either site, talking to team members about experiments and prioritising timetables. Afternoons then give me the opportunity to write papers, grant proposals or deal with the myriad of queries stemming from our research.

Why is your work important?

Learning how drugs work against protozoa and how parasites become resistant to drugs is necessary given the importance of drugs in our efforts to control the devastating diseases caused by parasitic protozoa.

Trypanosomes in blood

Scanning electron micrograph of trypanosomes in blood, courtesy of Dr Laurence Tetley

Human African trypanosomiasis, sleeping sickness, reached staggering levels by the end of the 20th Century, an with estimated 300,000 people infected.

I was privileged to be involved in bringing a new compound forward through the early part of the 21st Century, and was amazed to see that the implementation of serious clinical trials alone was enough to have a major impact on the disease.

Since then other new compounds have come forward, money has been raised, and a concerted international effort has bought reported cases of sleeping sickness down to fewer than a total of 7,000 reported cases.

As part of our efforts to understand how drugs worked we introduced the new technology of metabolomics to trypanosome research about ten years ago, and have steadily introduced ever more sophisticated techniques to gain information on the inner workings of parasites.

The technology, though, is generic and we quickly began to use metabolimics to look at biological changes associated with drug action in a multitude of systems, as well as to see how biochemistry is perturbed in different disease states. Since genes and proteins are also part of the information cascade that leads to these changes in biochemistry we also incorporated genomics, proteomics and metabolomics into a single site, called “Glasgow Polyomics”.

Michael Barrett with metabolomics data emerging on an Orbitrap Q-Exactive

Over the last three years we have carried out several hundred projects ranging from the discovery of new biomarkers for stroke, and how drugs act in a multitude of diseases (including rheumatoid arthritis, malaria and bacterial sepsis) to investigating the fluctuating state of health of wildebeest by analysis of metabolites found in their tail hairs.

The metabolomics team are using mass spectrometry to study the authenticity of Burns’s poetry and have even been asked to study Martian rocks for isotopes that might indicate life on Mars!

As a Scottish-based facility, showing the public how whisky can be described in terms of its chemical composition – determined using the same machinery we use to look at the chemical composition of people’s body fluids – has been fun too.

What do you hope the impact of your work will be?

My immediate hope is that our work on sleeping sickness will make a positive contribution to the international effort underway with a hope of eliminating that disease by 2030. Longer term I hope that in having set up Glasgow Polyomics we can contribute to the amelioration of numerous other diseases.

How did you come to be working on this topic/in this field?

As an undergraduate in Zoology at UCL I went on an expedition to the Usumbara mountains in Tanzania in 1985. The inequalities in health I witnessed there were eye-opening. This was at the beginning of the molecular revolution, and it seemed we should be readily able to understand the causes of disease and also to defeat them. I decided then to carry out a PhD in Parasitology and have continued in this area until now.

How has Wellcome funding helped you/your research/your career?

Wellcome Trust funding has been critical throughout my career. From my first post-doc, my first project grant as an independent investigator, through to today the Trust has been a key funder in my research.

Of course this goes back to Sir Henry Wellcome’s own interest in tropical diseases which has meant the Trust continued to back research in this area even when it had become unfashionable elsewhere. Today, the funding the Trust provides through its Institutional Strategic Support Fund (ISSF) award is the cornerstone of our developments at Glasgow Polyomics. The core funding of the Wellcome Trust Centre for Molecular Parasitology has also been vital on enabling us to apply new technologies such as those in Polyomics to diseases associated with the world’s poorest people.

Whats the most frequently asked question about your work?

“Can you really do that?”

The mass spectrometry based approach to untargeted metabolomics reveals the relative quantities of hundreds or even thousands of individual metabolites in a given system in just a single experiment.

Which question about your work do you most dread – and why?

“Is 2030 a realistic target for the elimination of sleeping sickness?”

The gains made against trypanosomiasis have been incredible in the twenty first Century. However, the end games for other infectious diseases, like polio and Guinea worm, show how difficult elimination can be. Yet we are already witnessing funding agencies turning their backs on the disease when confronted with choices on where to put their resource.

Trypanosoma brucei metabolic network present at the trypanocyc database

Trypanosoma brucei metabolic network , present at the trypanocyc database

Tell us something about you that might surprise us…

I climbed Mont Ventoux as the last of a series of high mountains in France by bicycle this summer. (I’ve always loved sport although my contemporary physique offers few clues to this!).

What keeps you awake at night?

Excitement about a new discovery and its meaning can keep me awake with an energised buzz. Worries about deadlines, sustainability targets and the like can keep me awake in a less energised state too.

Whats the best piece of advice youve been given? 

Decide what it is you want to do and pursue that irrespective of what others tell you about its worth.

The chain-reaction question, set by our previous spotlighted researcher Dr Faith Osier, is: What makes you really happy about your work and research?

Finding something new and of obvious impact and then validating the finding. Such discoveries are happening at an accelerated rate in Glasgow Polyomics, and telling our partners that they appear to have a really significant observation in their data is hugely gratifying.

You can find out more about Professor Mike Barrett’s work on his University of Glasgow researcher page and by visiting the Glasgow Polyomics website.

 

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