Past and present
Metabolomics (including lipidomics) has matured significantly in recent years. So far, a trait of this field is that there is not one generic method to capture the very diverse and complex metabolome due to the large variation of physicochemical properties, biological function and concentration of metabolites present in biological samples. Therefore, a range of metabolomics methods based on NMR or MS are used to analyze the metabolome. In most cases absolute concentrations are not yet reported, but rather relative concentrations. The relevance of metabolomics for the life sciences has been demonstrated by addressing some important clinical and biomedical questions: (i) inborn error of metabolism were identified by combining genomics and untargeted metabolomics, (ii) Early metabolic biomarkers for Alzheimer were identified that could be replicated in several cohorts and (iii) metabolomics has identified key pathways in metabolic syndrome, cancer and immunology. These findings can help to identify novel treatment options (evidenced by e.g. drug companies directing focus on metabolic targets). In recent years, metabolomics has become able to capture the cumulative effect of the environment, the so-called exposome, on health and disease, and is therefore ideally complementary to genomics to assess someone’s actual health status and predict the onset of diseases.
Metabolomic data can be now modelled at the cell level, multi cell/organ level, and even in complex systems such as the gut microbiome and include cell-cell interaction via the microenvironment. The use of metabolomics in research approaches has strongly increased, yet the metabolome cannot be studied by one analytical method alone due to the biochemical and physicochemical diversity of metabolites and lipids. Therefore, extended metabolite coverage requires employing NMR- and a variety of MS-based approaches. Most labs do not have the critical mass of infrastructure and expertise with well-trained personnel to develop and support a high throughput metabolomics lab capable of advancing metabolomics technology and enabling novel applications.
Although it is now widely seen that measuring and analyzing the complex longitudinal high-dimensional data is mandatory to make progress in research, current metabolomics platforms have limited throughput, making it difficult to analyze time-resolved data. Also, obtaining an in-depth metabolic profile is still challenging, as many metabolites are not identified yet. Metabolomics has been applied in the last decade for mechanistic studies in cell and animal systems. Methods have been developed to study dynamics of metabolism using stable isotopes. To enable novel, integrative studies, making use of large cohorts and multiple time points, we need to continuously develop means to achieve – clinically applicable – higher throughput.
Challenges to be addressed by the infrastructure
Metabolomics will be used to detect the onset of diseases, to reveal disease mechanisms, and to choose the proper prevention and treatment strategy.
To make this possible, we will address the following main challenges:
(1) higher throughput, lowering costs and sample needed to enable single cell and population-based metabolomics analyses
(2) absolute quantitation for more metabolites enabling the combination of different studies and additional data analysis strategies such as fluxomics
(3) studying the dynamics within and between cells and tissues and the human body.
(4) translation and implementation of metabolomics findings into the clinic
Thomas Hankemeier is professor of Analytical Biosciences and head of the Division of Analytical BioSciences at the Leiden Academic Centre of Drug Research at Leiden University and Medical Delta Professor of Translational Epidemiology at the Erasmus MC. Pioneering innovation in metabolomics technology as well as analytics, he has developed novel technology to miniaturize the setup and advance metabolomics methods towards high throughput using microfluidics. Thomas is initiator and scientific director of the Netherlands Metabolomics Centre; a €53M public-private research program (2008-2013). He was chairman of the 2010 Metabolomics conference in Amsterdam, member of the Board of Directors of the International Metabolomics Society. He aims to realize personalized medicine and prevention by translating changes in pathways and biochemical networks during diseases to possible treatment options. He has developed a microfluidic 3D cell culture technology, and is cofounder of MIMETAS, the worldwide first organ-on-chip company.