Award for fundamental research2021
Ammodo Science Award
Fundamental scientific research is essential for extending the limits of our knowledge. The Ammodo Science Award therefore stimulates specifically fundamental science. The Award covers all scientific disciplines, divided into four fields: Biomedical Sciences, Humanities, Natural Sciences and Social Sciences.
Nomination & selection
The Ammodo Science Award for fundamental research consists of eight sums of money, each of 300.000 euros. The advisory committee selected for each scientific domain puts forward two candidates for the Award chosen by them out of all the nominations received within that domain. The next nomination round for the fifth edition of the Ammodo Science Award will start in the spring of 2022.
The Ammodo Science Award is for outstanding, internationally recognised mid-career scientists working in the Netherlands who were awarded their PhD no more than fifteen years ago. In 2015 the first eight laureates received the inaugural Awards.
DNA could rightly be called the molecule of life. It ensures that all processes in our body function properly. We have a lot of it: every microscopic cell in the human body contains as much as two metres of DNA. And if you could put the DNA of all the cells of one human being in a line, such a line would stretch back and forth to the moon 50,000 times. But DNA is vulnerable: it is almost continually being damaged. Merely through breathing, tens of thousands of instances of damage occur in each cell in the body every day – even without additional environmental risk factors such as UV light, cigarette smoke or adverse substances in our food.
In short, keeping all our DNA in good shape is an enormous challenge, and yet it is very important to do so because cells with damaged DNA can mutate and, may for example, develop into tumours. Fortunately, every cell also has all kinds of DNA damage repair mechanisms. For decades the Guardians and Caretakers of the Genome research team at the Erasmus MC in Rotterdam has been focusing on how exactly cells do in fact repair themselves. What is unique about this team is that they study this process, in relation to ageing and cancer, at difference levels of complexity: In relation to cancer and ageing, for example, they are looking atfrom single individual molecules to as well as at complete physiological processes within the cell or the patient.
If you could put the DNA of all the cells of one human being in a line, such a line would stretch back and forth to the moon 50,000 times.
The team’s research has led to many ground breaking discoveries, as a result of which the Rotterdam research group has been at the forefront of this field worldwide for many years. Thus, whereas in the 1980s very little was known at all about DNA repair and which proteins or genes were involved in the process. This changed when the research team identified the very first human gene proven to be involved in repairing DNA damage. In the years that followed, more and more DNA repair genes were discovered. It also became clearer which proteins are involved in DNA repair, what their role is and how they are constructed. Almost all the main factors involved in DNA repair have now been clearly identified and described.
The Rotterdam researchers have also discovered that a malfunctioning DNA repair system can lead not only to mutations and cancer, but also to accelerated ageing. Normally almost all damage to DNA is repaired but if the repair does not succeed for example because the repair system itself breaks down, a cell has only a few options. It may die and must then be replaced with a new cell, or it will remain alive in a damaged state. But if too many cells in a single organ become damaged the functioning of that organ deteriorates, and this is the basis of ageing.
The team carries out fundamental research: their primary focus is on understanding how the processes described above work. The importance of this knowledge for patients is not always immediately clear but the discoveries made have ultimately proven to be extremely relevant to medical practice. For example, they have led to the development of a method that allows doctors to determine whether or not a particular DNA repair system in the tumour cells in an individual patient with breast cancer is working. If it isn’t, the patient can benefit greatly from a drug that shuts down only tumour cells with a defect in their DNA repair system, while leaving healthy cells alone.
A malfunctioning DNA repair system can lead not only to mutations and cancer, but also to accelerated ageing.
Having received the Award, the research group can now take a new and ambitious further step forward with almost all the main elements involved in DNA repair known, the team wants to understand how the different DNA repair processes are interrelated. To be more precise, they want to know how the molecular chaos of random molecular interactionsand dynamic interactions can give rise to can give rise to biological reactions and cellular structuresproperties. It can seem as if everything that happens in a cell is random and yet at the same time, we now know that orderly repair processes can arise from this apparent chaos. How this is possible and how these processes are interconnected is the ‘avant-garde challenge’ that the team is now embarking upon.
While the focus of the team’s research in the 1970s was limited to somatic cell genetics, their multidisciplinary focus is now on the interface of biology, chemistry and physics. Over the years the research group has always been able to bring in the relevant experts and to create the technologies needed for their new research questions. For example, there are researchers who can custom build exactly the microscopes needed to answer their current research questions. Another team member has developed special techniques in electron microscopy which make it possible to look at DNA molecules in higher resolution.
Another special achievement was that in the absence of a science faculty in Rotterdam, the team established and developed its own completely new Nanobiology course, in collaboration with Delft University of Technology (TU Delft). As far back as 2012, the researchers realised that it was going to be important for future success to have team members trained in physics and mathematics in addition to those who specialised in biology. Moreover, new ways of thinking and a new language were needed to understand these sorts of complex molecular interactions. So Nanobiology students are now learning to use concepts from physics and the language of mathematics to fathom the complexity of biology, of great benefit to the team as a whole.
In the longer term, the research the team is doing now may not only lead to enhanced scientific knowledge but may also lead to major advancements in medicine as well.
The outstanding quality of the research team and the ground breaking achievements of its previous research is known worldwide, as well as the importance of their new research project into how biological reactions and cellular properties arise out of random and dynamic molecular interactions. If they can discover how molecular behaviour is disturbed by illness and how it operates when human beings are healthy, then this may lead to doctors being able to intervene in time if something does go wrong. In the longer term, the research the team is doing now may not only lead to enhanced scientific knowledge but may also lead to major advancements in medicine as well, not only in the form of more specifically tailored treatments for patients with cancer, but also of the slowing down or prevention of premature ageing diseases. As the team itself says: “We are constantly feeding ideas into the pipeline, ideas without a predictable application. But we are convinced that some of these ideas will ultimately lead to a more successful fight against diseases such as cancer and Alzheimer’s.
Team members (f.l.t.r.): Claire Wyman, Jurgen Marteijn, Wim Vermeulen, Arnab Ray Chaudhuri, Joyce Lebbink, Roland Kanaar, Jan Hoeijmakers, Miao-Ping Chien.