Manager of the CTU: Dr Olivier Chevallier
Academic Lead for the CTU: Dr Brian Green
Our mass spectrometry facility is one of 5 Core Technology Units (CTUs) for the Faculty of Medicine, Health and Life Sciences and it is housed within the Advanced ASSET laboratory at IGFS. We are part of the Waters Centers of Innovation Program and possess a range of state-of-the-art hyphenated MS instruments. Various LC-MS/MS and GC-MS are available for tailored measurements of predetermined analytes such as toxins, pesticides or targeted metabolomic, as well as high resolution instruments (QTof) coupled to UPLC for non-targeted metabolomic analysis, or to ambient sampling interfaces such as Rapid Evaporative Ionization Mass Spectrometry (REIMS) or to Direct Analysis in Real Time Mass Spectrometry (DART-MS) which allow holistic profiling of tissue samples with minimal sample preparation.
Examples of some Advanced Mass Spectrometry:
Current forensic testing approaches to detect both emerging and existing drug abuse are inadequate in many respects with recent high profile examples in athletics and horse racing a clear indication of testing regime failure. Testing is problematical, costly and inefficient, and whilst mass spectrometry analysis has enabled the targeted analysis of samples for the presence of multiple compounds, effective testing still requires prior knowledge on the types of compounds being used. This thereby limits the range of hazardous and illegal chemicals which can be detected and consequently MET-A-FOR ITN project (2015-19) funded by the Horizon 2020 Framework Programme of the European Union (grant agreement no. 642380) aims for a major scientific breakthrough towards applying current and emerging technological developments in the field of mass spectrometry and metabolomic profiling to this issue. Using the combined expertise of academic and industrial beneficiaries a unique advance in drug abuse detection in animals will be developed based on initial indirect screening to identify biological responses in animals to exogenously administered drugs, followed by targeted confirmatory analysis of drug metabolite presence in suspect samples. This approach will facilitate more comprehensive screening for the abuse/misuse of a vast array of drugs as it will not be solely reliant on the targeted detection of single or selected compounds of abuse, but on the detection of the metabolic effects of these compounds in their totality on animal biological systems. This will enable detection of the use of illegal and health threatening compounds in food producing and performance sport animals irrespective of whether these chemical agents are of known/unknown structure. Advances in this field will ensure that European animals are thoroughly tested for the presence of harmful/illegal substances and that the integrity of our performance sport and food production animals are of the highest level.
Food fraud has become a topic of major concern over the past few years mostly due to major incidences such as the 2008 Chinese melamine scandal and the 2013 European horsemeat scandal. Like many food commodities, fish supply has succumbed to food fraud on a global scale. A recent review identified that on average 30% of products sold are either misrepresented or mislabelled. Rapid evaporative ionisation mass spectrometry (REIMS) is one of the newest forms of Ambient Mass Spectrometry (AMS) technique and it was created for medical research purposes such as tissue identification and bacterial identification applications. A collaborative project supported by Waters Corporation and BBSRC was recently initiated in order to evaluate the potential of REIMS technology for food fraud application. In our current study, REIMS was applied to five commercially popular white fish species (cod, coley, haddock, pollock and whiting) and investigated as to whether REIMS based lipidomics could be applied to fish speciation by measuring and comparing the phospholipid profiles of each species. A database with over 300 authenticated fish sample was developed alongside a chemometric model which is able to differentiate and classify accurately the various fish species studied. Further applications of REIMS technology such as meat speciation for instance are currently under development.
Colorectal and liver cancer are the third and sixth most common cancers globally. Genetic risk factors are being extensively researched, however the role that exposure to water and food toxins play is much less well understood. Increasing numbers of human poisonings globally are caused by freshwater microcystin toxins due to climate change and pollution. These toxins have been linked to increased cancer risks but there is no means of measuring the extent of human exposure and thus determining their importance. Funded under the Science Foundation Ireland-Department for Employment and Learning Partnership, the aim of the project is to identify and validate biomarkers of microcystin exposure and undertake epidemiological studies in high risk populations. Interrogation of blood and tissue samples will be performed in our state-of-the-art metabolomics facility using advanced techniques such as high resolution mass spectrometry and high performance computing bioinformatics. Specific antibodies will be generated to the identified biomarkers and incorporated into a high through-put microfluidics sensor platform with subsequent validation. Finally samples will be obtained from high risk cohorts and tested for the presence of both microcystin toxins and the biomarkers of exposure. This study will play a key role in investigating the role of these toxins in liver and colorectal cancer.
Dementia poses a significant challenge for our ageing population. Alzheimer’s disease is the single cause of dementia estimated to affect 4 to 6 million people in Europe, but also >35 million people around the world. The cause is not known and the ‘Holy Grail’ of dementia research is the discovery of a simple blood test enabling reliable, accurate and early diagnosis of disease. Some progress has been made in studying the changes in gene expression, protein profiles, and in brain images, however, metabolomics offers a powerful alternative to these methods as it makes use of exponential improvements in analytical technologies. Funded by Alzheimer’s Research UK and Invest NI we are one of a small number of laboratories in the world to have investigated Alzheimer’s disease using the wide range of metabolomics platforms currently available. For more than 8 years we have building our capabilities in this area and have been accessing local and international repositories of Alzheimer’s-relevant material tissue/blood/cerebrospinal fluid samples. We are working closely with clinical experts and scientists in NI, but also across the UK (Bristol) and internationally (US, Germany). During the course of our research we have systematically developed a method which accurately discriminates patients with Alzheimer’s disease from healthy volunteers. Initially, we have demonstrated that this approach works successfully in disease models, then in post-mortem human tissue samples, but more recently we have demonstrated that the approach also works with blood samples from living patients. In short, mass spectrometry-based metabolomics provides tool which captures the majority of metabolite changes in Alzheimer’s disease, and work is now needed to convert this into a meaningful diagnostic test for pre-symptomatic disease.
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