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Team TFS
Team TFS

capturePhenome Centre Birmingham

The Phenome Centre Birmingham is one of only a few institutes in the world set up as, in their own words, ‘a state-of-the-art metabolic phenotyping facility to conduct small-scale and large-scale studies in medical research and stratified medicine.’ Opened on May 23rd of this year by Professor Sir Mark Walport, Government Chief Scientific Advisor and Head of the Government Office for Science in the UK, Phenome Centre Birmingham has big goals.

Sir Mark delivered a talk to kick off the day’s proceedings entitled ‘Precision Medicine: The challenges and opportunities’ which I think would be worth your time to watch if you have an interest in precision medicine. There are several other talks worth watching from that day’s proceedings.

Precision Medicine, the NIH and a Small Rant

Before I continue to describe the aims of the Phenome Centre and why you and I should be interested in the phenome, I will take a moment to remind us all of what precision medicine (also stratified medicine) is all about and to have a very small rant. According to the National Institutes of Health (NIH) precision medicine is ‘an emerging approach for disease treatment and prevention that takes into account individual variation in genes, environment, and lifestyle for each person.’ Both the UK and USA have recently funded initiatives to develop precision medicine for their populations.

These are lofty goals – to treat people as if they were different from each other and with different needs, and to treat disease that is, but also disease that is yet to be (and may never be if we are clever), based on the principle of ‘the five rights of medication administration’ of right patient, right drug, right route, right time and right dose. People are not the same and treating them as if they are, as if a statistic, has never been the best way to deliver healthcare.

Why metabolomics?

Short rant over and back to Phenome Centre Birmingham and its currently rare research focus.

Firstly what do we mean by phenome? Well, just as the genome signifies all of an organism’s genes and the proteome similarly so for protein (although a proteome can be at the level of an organism, type of tissue, cell type, etc.) then the phenome represents the sum total of an organism’s phenotypic traits, such as for you and me, eye colour (mine are usually grey). While a phenotype has a basis in the genome (genotype), phenotypic expression may also be influenced by other factors such as the environment, and for people, life style and realistically, simple chance. Something might just happen to me that might not happen to you.

Why are we interested then in metabolomics - the study of the complete collection of metabolites, the metabolome - as a tool for phenotyping? Why don’t we simply investigate the genome to tell us about the phenome? Simply put, because the genome is not the phenome. They are not the same. They are not even equivalent. You will know the paradigm of DNA makes RNA makes protein. It is a fundamental (although simplistic) tenet of biology. The genome acts to provide information to, for example, create structures such as muscle and enzymes to catalyse reactions in the cell. It is relatively constant during your lifetime, with only small changes, such as mutations, generally occurring. Therefore, the genome is relatively static and unchanging. But if, for example, we wish to detect changes as we age that might be precursors of illness or be in some other way informative about our current state of health and maintaining that health then we need to look elsewhere than the genome.

The metabolome, unlike the genome, is not static but rather is responsive, and rapidly responsive, to change. That makes the metabolome extremely interesting. Metabolites are key biochemicals in all living systems. They are central to metabolic activities in the cell, including the breakdown of food into metabolites (catabolism) and the synthesis of other metabolites and biochemicals, including proteins, RNA and DNA (anabolism). Metabolites are also important in the regulation of biochemical processes, signalling processes, and in the making of cellular structures. As with the proteome, there are many metabolomes. For example, the blood metabolome will be different to the urine metabolome and both of these metabolomes are readily accessible for measurement of metabolite levels.

Back to the original question: why metabolomics? The metabolome changes in response to environment and lifestyle. Thus, and now to the point, we can use this dynamic nature of the metabolome to our advantage to understand mechanisms of disease, to identify markers that can be applied to prognosis, diagnosis and in treatment response to disease in stratified or precision medicine and ultimately change people’s lives for the better.

Why am I interested in Phenome Centre Birmingham?

Perhaps you can guess? I love technology. I love science. I love when science and technology lead to change that improves our lives. One of the biggest problems facing us all today (among a few such) is that we live longer lives. Problem... how is that a problem? Because although we live longer lives, those extra years come with a burden, a severe burden - morbidity. We are often not healthy in our old age. Many of us, as we age, are aging in a thoroughly unhealthy way – for example, we get diabetes, we get inflammatory diseases like rheumatoid arthritis, we suffer from hypertension and its consequences and I can go on and on. If I am lucky enough to live a long life, although with my family history I am not sure of that, I would dearly love those extra years to be mostly spent in good health, not suffering and pain. So an institute like Phenome Centre Birmingham presents an opportunity for us all to enjoy improved future good health. In Birmingham they apply cutting edge technology like liquid chromatography-mass spectrometry (LC-MS) applied to metabolomics to perform studies, involving hundreds or even thousands of samples, that will lead to a better understanding of how to stay healthy into old age. Their goals are these:

‘Phenome Centre Birmingham conducts metabolic phenotyping studies with the following objectives

  • To understand molecular mechanisms associated with human ageing, disease onset and progression  

  • To identify molecular targets for nutritional, exercise or drug interventions

  • To identify metabolic biomarkers for stratification of the human population to be applied in risk stratification of developing a specific disease, in diagnosis of a disease, in defining progression or remission from a disease, and in the identification of responders and non-responders to nutritional, exercise or drug interventions’

These are lofty and worthwhile goals.

A fun day out in Birmingham

I recently visited Phenome Centre Birmingham at the University of Birmingham, UK to talk to Dr. Warwick Dunn, Director of Mass Spectrometry there and Senior Lecturer, and Prof. Mark Viant, Chair in Metabolomics and Executive Director of Phenome Centre Birmingham, about what their aims are for metabolic phenotyping. Prof Viant: ‘Phenome Centre Birmingham was developed in the UK in response to a need to increase the capability for and the capacity for large scale metabolic phenotyping so that instead of studying a few tens or hundreds of subjects we can study thousands of subjects. This greatly increases our statistical power and ability to conduct clinical research.’ So, in brief, this larger scale of analysis is likely to produce better data to understand metabolic changes associated with ageing and disease that could then lead to advice on how to intervene to stay healthy, through for example diet or exercise, and how to identify changes to health with metabolic biomarker assays.

One of the forward-thinking ways in which Prof Viant and his colleagues are working is that they have placed a mass spectrometer at the Institute for Translational Medicine nearby (it is literally a short walk away) so that the research findings of the Phenome Center can then be more readily translated towards clinical practice. This is a pragmatic model of how to move research findings efficiently from the bench to the bedside.

Prof Viant explained what he hopes to achieve in the next few years, ‘Our goals at Phenome Centre Birmingham are ambitious, within 5 years from now we want to have analysed literally hundreds of thousands of subjects and to have contributed significantly to the UK’s vision for stratified medicine.’ Health services are experiencing ever increasing cost. Metabolomics is a powerful technology for precision medicine which shows promise, particularly in cancer with its distorted metabolism, of improved outcomes but also there is expectation that healthcare costs can be controlled by the adoption of precision medicine approaches.

Both Prof Viant and Dr Dunn describe their work, their hopes and expectations for metabolic phenotyping at Phenome Center Birmingham in this video.

And finally

Precision medicine is a big deal. It isn’t about completely different types of medicine or new technology but is more about a different way of ‘performing’ medicine. It is about treating people more uniquely although it isn’t really completely personalized. One person is not the same as the next. One size does not fit all. One drug will not treat all people with a specific illness successfully. Precision medicine/personalised medicine (while not literally the same, many of us interested in applying medicine more effectively and more personally are to some extent using the terms interchangeably) could, should and will lead to longer lives lived more healthily. We probably all have relatives who are older and who suffer ill health pretty much all the time. They have several chronic complaints that cause them discomfort, immobility and perhaps even downright pain, not just aches. We cannot live forever but we want that living to be well lived.

For more information on metabolomics I refer you to another article.

For Phenome Centre Birmingham click here.

A video with my interview with Prof. Viant and Dr. Dunn is here: Phenome Centre Birmingham.

A webinar from Dr. Dunn is also available here: The Promise of Mass Spectrometry-Based Metabolomics for Clinical Research.
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