Gravitation grant for Exposome-NL with Sasha Zhernakova

26 million for research on the impact of non-genetic factors on health

Which groups of people are affected by certain chronic diseases, and which groups are not? The answer depends on both genetics (30%) and the exposome (70%). By exposome we mean all kinds of factors in everyday life, including what we eat and drink, the air we breathe, our social interactions and lifestyle choices such as smoking and exercise. Individuals’ biological response to these factors also forms part of this exposome. Much remains to be discovered about the exposome, and therefore about the development of chronic diseases.A consortium led by Professor Roel Vermeulen, affiliated with Utrecht University and University Medical Center Utrecht, will investigate which factors of the exposome are important for health and how these factors work. To this end, the consortium has been awarded 18 million Euros from the prestigious Gravitation Grant, with the participating institutes themselves contributing an additional 8 million euros.

Vermeulen: 'In their daily lives, people make all kinds of choices that have a major impact on their health. Thanks to the grant, we are able to identify all non-genetic risk factors for the health of the Dutch population.' Much is already known about the human genome, but researchers now also wish to systematically analyse the human exposome for the first time. 'We know that the disease burden of people with chronic illness is largely influenced by the exposome. That’s why this grant is so important. We will start by researching the causes of cardiovascular disease and type 2 diabetes. The techniques and insights from this study can also be applied to other chronic conditions.'

'This grant will allow us to make major progress in the systematic analysis of all non-genetic risk factors for the health of the Dutch population. These insights should lead to better prevention of chronic diseases.' Rick Grobbee, co-initiator (UMCU)

Collaboration
Vermeulen emphasises the complexity of the research, 'Unravelling the impact of non-genetic factors on our health is not easy, but with this unique collaboration between physicians, molecular biologists, epidemiologists, geographers and chemists, we think we should succeed.’ The research team will operate under Vermeulen’s leadership (Utrecht University and University Medical Center Utrecht) and includes five other top scientists: Mei-Po Kwan (Faculty of Geosciences, Utrecht University), Rick Grobbee (University Medical Center Utrecht), Thomas Hankemeier (Leiden University), Sasha Zhernakova (University Medical Center Groningen, RUG) and Joline Beulens (Amsterdam UMC).

Sasha Zhernakova leads research into internal exposome at UMCG

‘Within the Exposome-NL project, we at the UMCG will focus on the internal exposome – the environmental factors within our body.’ Sasha Zhernakova explains. 'The most active environmental factor inside us is the human microbiome, the community of microorganisms that live in our bodies. The majority of these microorganisms reside in the human gut, and this gut microbiome includes hundreds of unique bacteria, viruses and protozoa. Together, these organisms form a community that is highly variable between individuals. These microorganisms form a natural symbiosis with their human host, and are influenced by both environmental factors and host genetics and physiology.'

'We have previously studied how the gut microbiome mediates the effect of food and drugs on individuals and how it mediates the interaction between host diet and genetics (Zhernakova et al, Science 2016; Imhann et al, Gut 2015; Zhernakova et al, Nat. Genetics 2018; Bonder et al, Nature Genetics 2017). The new Gravitation project will enable us to investigate, on a large scale, the role of the microbiome in interaction with various environmental factors, including air pollution, the chemical environment and specific dietary and lifestyle factors.'

'Moreover, environmental factors can also affect other biological systems, such as epigenetics (e.g. methylation of our genes), gene expression, the levels of proteins and metabolites produced and other biological pathways. We will therefore perform extensive multi-omics studies to understand how environmental factors influence the host’s body and pathways and lead to diseases (and aging), applying so called “big data analysis” to integrate all host and environmental factors.'

This work will be done in collaboration with Lifelines, a unique large population cohort from Groningen, Drenthe and Friesland that is collecting extensive longitudinal data about the exposome. This data includes information on participants’ diet, socio-economic factors, lifestyle and environment, as well as many others factors. We will link this environmental data with microbiome, genetics and other multi-omics measurements to build a more holistic view of how environmental factors can impact the health of an individual.

Gravitation
By means of the Gravitation program, the government encourages research by groups of leading scientists in the Netherlands so that they become global leaders. To reach this level, researchers must carry out innovative and influential research in their field. The Ministry of Education, Culture and Science has asked the Netherlands Organisation for Scientific Research to carry out the selection procedure for this funding programme.