Babraham scientists contribute to international effort to produce maps of human metabolism
Babraham scientists, collaborating with an international consortium of researchers from 35 institutions across the world, have produced an instruction manual for the human genome that will provide unparalleled insights into the relationship between an individual’s genetic make-up and their lifestyle. The paper, published online this week in Nature Biotechnology, provides the best model yet to explain why individuals react differently to environmental factors such as diet or medication. It represents the most comprehensive resource on the biochemistry of human metabolism currently available. This knowledge will have a direct impact on strategies for personalised healthcare, ultimately bringing treatments that are tailored to an individual’s biochemistry closer to the clinic.
“This research is the second, important stage of our understanding of the human genome,” said Professor Pedro Mendes, from The University of Manchester’s School of Computer Science, which led the study along with the University of San Diego in the US. “If the sequencing of the human genome provided us with a list of the biological parts then our study explains how these parts operate within different individuals. “The results provide a framework that will lead to a better understanding of how an individual’s lifestyle, such as diet, or a particular drug they may require is likely to affect them according to their specific genetic characteristics. The model takes us an important step closer to what is termed ‘personalised medicine’, where treatments are tailored according to the patient’s genetic information.”
The research, which involved scientists from Manchester, Cambridge, Edinburgh, Reykjavik, San Diego, Berlin amongst others, mapped 65 different human cell types and half of the 2,600 enzymes that are known drug targets in order to produce the network model. Co-author Professor Douglas Kell, Chief Executive of the Biotechnology and Biological Sciences Research Council (BBSRC) and Professor of Bioanalytical Science at the Manchester Institute of Biotechnology said, "To understand the behaviour of a system one must have a model of it. By converting our biological knowledge into a mathematical model format, this work provides a freely accessible tool that will offer an in-depth understanding of human metabolism and its key role in many major human diseases. This study offers the most complete model of the human metabolic network available to date to help analyse and test predictions about the physiological and biochemical properties of human cells.”
Dr Nicolas Le Novère, who led the team at EMBL-EBI and is now a Group Leader in Computational Biology at The Babraham Institute, developed the data infrastructure and the common language the scientists needed to link models and related information. He said, “This is a model that links the smallest molecular scale to the full cellular level. It contains more than 8,000 molecular species and 7,000 chemical reactions manually checked using a crowd-sourcing approach – no single researcher could have built this alone. Having large collaborations like these, using open standards and data-sharing resources, is crucial for systems biology.”
Although many human diseases are due to metabolic defects, understanding the endless complexity of human metabolism is a significant challenge. Having a complete, ‘gold-standard’ metabolic model represents a major milestone in systems biology, enabling researchers to use computers to test what happens in a human cell. This resource is a major step towards achieving that goal.
The Babraham Institute, which receives strategic support from BBSRC, last week opened its new research building, designed to integrate all of the Institute’s research groups in one contiguous building and facilitate greater cross-talk between ‘wet’ and ‘dry’ science. Professor Michael Wakelam, Director of the Babraham Institute said, “This metabolic map is a goldmine for systems biologists aiming to understand the relationship between metabolism, ageing and disease. The recent establishment of computational biology research groups at Babraham underscores the increasingly vital role that computational biology plays in addressing the basic bioscience underpinning health and disease through international research consortia such as this.”
Publication details: A community-driven global reconstruction of human metabolism. Ines Thiele, Neil Swainston et al., (2013) Nature Biotechnology dx.doi.org/10.1038/nbt.2488 The metabolic model is available in EMBL-EBI’s BioModels Database in many different formats (go to www.ebi.ac.uk/biomodels-main/MODEL1109130000). 'Mapping Metabolism' - press release on the EMBL-EBI website
Notes to Editors:
About the Babraham Institute:
The Babraham Institute undertakes world-class life sciences research to generate new knowledge of biological mechanisms underpinning ageing, development and the maintenance of health. Our research focuses on cellular signalling, gene regulation and the impact of epigenetic regulation at different stages of life. By determining how the body reacts to dietary and environmental stimuli and manages microbial and viral interactions, we aim to improve wellbeing and support healthier ageing. The Institute is strategically funded by the Biotechnology and Biological Sciences Research Council (BBSRC), part of UK Research and Innovation, through an Institute Core Capability Grant and also receives funding from other UK research councils, charitable foundations, the EU and medical charities.
The Biotechnology and Biological Sciences Research Council (BBSRC) is the UK funding agency for research in the life sciences. Sponsored by Government, BBSRC annually invests around £450 million in a wide range of research that makes a significant contribution to the quality of life for UK citizens and supports a number of important industrial stakeholders including the agriculture, food, chemical, health and well-being and pharmaceutical sectors. BBSRC carries out its mission by funding internationally competitive research, providing training in the biosciences, fostering opportunities for knowledge transfer and innovation and promoting interaction with the public and other stakeholders on issues of scientific interest in universities, centres and institutes.
The EMBL-European Bioinformatics Institute (EBI) is part of the European Molecular Biology Laboratory (EMBL) and is located on the Wellcome Trust Genome Campus in Hinxton near Cambridge, UK. The EBI grew out of EMBL's pioneering work in providing public biological databases to the research community. It hosts some of the world’s most important collections of biological data, including DNA sequences (ENA), protein sequences (UniProt), the genomes of animals and plants, three-dimensional molecular structures, data from gene expression experiments, protein-protein interactions and reactions and pathways. EMBl-EBI's many research groups are continually developing new tools to support the biocomputing community. EMBL-EBI plays an important role in the 1000 Genomes Project and coordinates ELIXIR, the emerging research infrastructure for life science data in Europe. www.ebi.ac.uk