Metabolomics

Metabolomics can be broadly regarded as the measurement of the thousands of metabolites present in a biological system at any given time. This can provide a sensitive snap-shot of the physiology of the cell (or biofluid) and how it is impacted by environmental and genetic factors. More than that, metabolomics is a powerful method for revealing novel or unanticipated metabolites and metabolic pathways, while exquisite detail of metabolic flux activity can be measured. 

Bespoke approaches

Here at the Crick, we are dedicated to the development and implementation of cutting-edge, tailored metabolomics techniques. Metabolomics-based projects are designed on a case-by-case basis, allowing you to achieve the answers you need to your biological question. Metabolite profiling, metabolic foot-printing, and stable isotope labelling techniques can be employed for the specific needs of a given study. We have considerable experience in metabolomics project workflows, including study design and development, metabolite extraction techniques, sample preparation, data acquisition, and data analysis. We use bespoke analytical approaches, chemometrics, bioinformatics, and statistical rigour to ensure that the data provided can be interpreted easily and with confidence. 

Repertoire

The field of metabolomics is as broad as it is young, and at the Crick we are focussed on a number of key areas.

Targeted and Untargeted Analyses: We specialise in targeted metabolomics, using tailored methods in order to study specific metabolites or metabolic pathways. We also perform untargeted analyses, employing more global profiling approaches in order to determine difference between biological samples and their causes. We are developing methods in order to improve our coverage of metabolite detection.

Metabolic Flux Analysis: An exceptionally powerful tool that we regularly use is stable isotope labelling. Here, we can add an isotopically-labelled form of a substrate (often a carbon or nitrogen source, such as 13C-glucose or 15N-glutamine) and trace incorporation into metabolic pathways. This provides invaluable information on the metabolic activity of the cell and enables the delineation of complex metabolic pathways.

Lipidomics: Analysis of polar metabolites accounts for approximately two-thirds of the Metabolomics STP workload, with lipidomics making up the remaining amount. We primarily study fatty acids, DAGs, TAGs , and sterols, and we are currently developing further lipidomics techniques in order to enable detection of further classes of lipids.

Data analysis: Data analysis is a sophisticated and necessary aspect to metabolomics projects. The methods used can vary considerably depending on the experimental requirements and can vary from the initial data extraction (peak-picking, integration, and identification), right through to data processing (quantifications, label incorporation, isotopologue analyses), pattern recognition (principal component analyses, hierarchical cluster analyses, component variability analyses), and statistical approaches (t-tests, ANOVA analyses, Volcano plots, Z-transformations, etc).

Data analysis

Data analysis (Click to view larger image)

Method development: Metabolomics is still very young and method development is still very much ongoing for many aspects of this research. Along with methods we are developing in-house, we are also interacting with some of the World's leading metabolomics groups in order to maintain excellence of operation, while continuing to develop bespoke methodology and integrate cutting-edge techniques into our workflows. This includes sample preparation, statistical rigour, and - especially - data analytics and chemometric techniques. 

Instrumentation

The Metabolomics STP represents a recent and substantial investment in the scientific future of the Francis Crick Institute. Metabolomics is a multi-platform and multi-disciplinary science and the Crick is home to some of the world's leading mass spectrometry (MS) and nuclear magnetic resonance (NMR) instruments dedicated to this purpose. The Metabolomics STP is currently based at the Mill Hill site and consists of 2 Thermo Fisher liquid chromatography (LC)-MS (Q-Exactive Orbitrap and Exactive-plus) systems and 3 Agilent gas-chromatography (GC)-MS (GC-MSD and GC-triple quadrupole, with additional chemical ionisation capabilities) systems. Also at our disposal are 4 Bruker NMR instruments. The MRC Biomedical NMR Centre houses Avance III 600 MHz, 700 MHz, 800 MHz, and 950 MHz NMR instruments. Each of these instruments has their own specialisation and together they provide a wide metabolite coverage. 

Contact

We are always happy to discuss metabolomics and how this exciting field can be used to advance your science. If you have any questions or would like advice on any aspect of the Crick Metabolomics STP, please contact James MacRae (james.macrae@crick.ac.uk).

James MacRae 

james.macrae@crick.ac.uk
+44 (0) 20 8816 2071