24 May, 2017
WormJam: A global community effort to build an in silico metabolic model that can help scientists elucidate how to slow down ageing A projected doubling in the global population of people aged ≥60 years by 2050 has major health and economic implications. Ageing was once thought to be a natural and inevitable process of decline, but scientists have discovered that there are genes and interventions that can slow down the ageing process. For example, genes related to nutrient sensing appear to slow down ageing when food intake is dramatically reduced. Despite this, we are still missing a clear picture of how metabolism can promote healthy ageing. A proper understanding of this link is important because it may be possible to prevent and/or delay unhealthy ageing using appropriate diets. It may also help to identify pharmacological interventions that can, for example, fool the body into acting as if nutrients were scarce even when they are not, slowing down ageing via nutrient sensing pathways yet avoiding the impracticalities of severe diets. Metabolism underlies every chemical reaction in the cell and is a highly complex process. Being so essential to life, core metabolic pathways are largely the same between complex organisms such as humans and much simpler organisms such as the versatile and tiny transparent worm C. elegans. Researching complex metabolic processes benefits from mathematical tools that can compute thousands of metabolic reactions quickly, and make overarching predictions. These tools are called “metabolic reconstruction models” and they have been built for single celled organisms, such as E. Coli, as well as for human cells, but are not yet widely available for multicellular organisms such as C. elegans. In April 2017, an international European network of C. elegans researchers (GENiE -- Group of C. Elegans New Investigators in Europe) held a workshop at the Babraham Institute, funded by COST (European Co-operation in Science and Technology) with the additional support of a Babraham Institute KEC grant. The workshop brought together around 30 scientists from 3 continents with the objective of building a comprehensive model to capture every metabolic reaction within the worm. To describe all reactions for a whole organism requires thousands of reactions and metabolites, joined together in complex pathways. Many gaps exist in our understanding of the details of metabolism across all organisms including C. elegans, and meticulous measurements are needed to identify missing components of the metabolic network. The effort required is too much for any one group, and that is why researchers from all over the world need to work together. Joining the predictive power of mathematical models with the genetic tools that allow experimental follow-up of key predictions will constitute a powerful 21st century workforce that will help to decode the best interventions that can slow down ageing. The workshop initiated a global interdisciplinary community to meet this challenge; the self-named community “WormJam”. Each participant is an expert in their own field, from bioinformatics to epigenetics, mass spectrometry to cell biology; together the community covers the full range of expertise needed for this ambitious project. WormJam is scheduled to meet again at the end of the year to continue the efforts towards metabolic reconstruction and will be open to a wider network of scientists. Watch this space for details of our progress.
24 May 2017