21 May 2021
What is the influence of non-genetic factors on our health, such as lifestyle, diet and exposure to harmful substances? The Exposome-Scan project, led by Leiden professor Thomas Hankemeier and Utrecht professor Roel Vermeulen, has been awarded 3.2 million euros from the NWO Investment Grant Large programme, to answer this question. With the grant, researchers from various Dutch institutes and medical centres will build a unique and large-scale open facility for research into the so-called exposome.
Nature versus nurture: the endless debate in science about hereditary and non-hereditary factors that influence our health. By now, scientists know a great deal about the influence of our hereditary factors. But environmental factors are at least as important, argues Thomas Hankemeier, who is a Professor of Analytical Biosciences. ‘They are responsible for seven out of ten chronic diseases. That is why we want to know which external factors have a major influence on our health and how these factors work together. Our ultimate goal is to use this knowledge to help people live healthier lives.’
We won't be using the grant to do our own research, but rather to build a laboratory in Leiden that will give researchers from all over the Netherlands the opportunity to study the exposome.
Exposome-Scan was founded to make that dream come true. The new project builds on the knowledge gained in the Exposome-NL and X-omics research programmes. Hankemeier: ‘We won't be using the grant to do our own research, but rather to build a laboratory in Leiden that will give researchers from all over the Netherlands the opportunity to study the exposome.’
And such a facility is unique in Europe. Even worldwide, there are few places where large-scale research into the environment and health takes place. ‘We want to make the Netherlands a worldwide pioneer in this field.’
What's also special is that the facility focuses on two types of research. ‘Firstly, studies in which we can measure thousands of chemical substances and nutrients in blood and urine on a large scale,’ says Hankemeier. Researchers can link the results to measurements of signalling substances that describe the biological consequences of these exposures. ‘That way, we can start to understand how diseases are influenced by our environment and lifestyle. We call that a Life-Scan. It allows us, for example, to look for chemicals that can later lead to dementia.’
The second type of research is aimed at uncovering the underlying mechanisms, Hankemeier explains. ‘For this, we use computer simulations, but also organs-on-chips: mini-organs that mimic the conditions in a person's body. This allows us to track in real-time what certain molecules are doing in our bodies.’
Anyone who submits a good research request will have access to the research facility and will be able to conduct research at Exposome-Scan at cost price. ‘This may include researchers associated with the NWO Gravitation programme Exposome-NL, but also other experts. Everyone is welcome. We provide the platform that makes high-quality research possible and guide the researchers with the measurements and how to interpret the data.’
‘Interpreting the data from the new lab is complicated. That is why we must develop a data infrastructure that makes it possible to properly identify the chemical and signal substances, in order to subsequently interpret all the data.
One thing is certain: the research at Exposome-Scan will generate mountains of data. Utrecht University will be responsible for analysing them, says Professor Roel Vermeulen, coordinator of the Exposome-NL Gravitation programme.
‘Interpreting the data from the new lab is complicated. That is why we must develop a data infrastructure that makes it possible to properly identify the chemical and signal substances, in order to subsequently interpret all the data. The application of artificial intelligence (AI) plays an important role in this. AI can help us not only to understand the complex data but also to understand how new insights relate to everything we already know.’
Sylvia Le Dévédec manages the research taking place at Leiden's Cell Observatory. ‘In the Cell Observatory, we zoom in on living cells using advanced microscopes. We will study the effect of the exposome on mini-livers and mini-kidneys.’ With this grant, a dream finally comes true, says Le Dévédec: ‘A state-of-the-art microscope that allows us to look live at signalling and metabolic changes, and that at the cellular level!’
Bob van de Water, Leiden Professor of Drug Safety, will measure biological disruptions at the cellular level. He uses fluorescent substances for this purpose.
‘We can now map the activity of a large number of chemical substances to which people are exposed at the cellular level. The unique thing about this programme is that we can now link the information about the exposome to cell biology. This will ultimately allow us to make a statement about the possible adverse health effects of individual chemicals. This puts us in a leading position worldwide.’
Hankemeier envisions a future where everyone can have his or her personal health profile drawn up. ‘That way you can offer the best personal care. An overly active immune system is sometimes not good, but neither is an inactive immune system. The balance is crucial, which is why we want to better understand what conditions throw our biological system off balance and how we can restore that balance. It would be great if we could offer each person such a personalised approach.’
NWO is supporting Exposome-Scan with a contribution of 3.2 million euros from the NWO Investment Grant Large. With this programme, NWO funds large scientific facilities in which scientists from across the Netherlands collaborate, often with international partners. Leiden University and Utrecht University lead Exposome-Scan. Other institutions involved are Erasmus MC, VU Amsterdam, LUMC, UMC Utrecht and the University of Groningen.
We know far less about the exposome than we do about the human genome. So far, we only understand about half of the disease burden for which we know the environment plays a role. If we want to prevent people from becoming ill, then we need to understand the other half too. We therefore want to systematically analyse the exposome for the first time. We will start with research into the causes of cardiovascular disease and type 2 diabetes. The techniques and insights from this research will also be applicable to other chronic conditions.Read More