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Biochemists Ruedi Aebersold and Matthias Mann will be awarded the Dr H.P. Heineken Prize for Biochemistry and Biophysics 2024. The jury commends their pioneering work in proteomics, and especially their prolific and seminal contributions to new techniques to study proteins in a system-wide context. As a result of their achievements, we better understand how healthy cells work and what goes wrong in disease. Never before has the prize been awarded to two independent scientists.

In 2024, it will be 60 years since Alfred Heineken introduced the very first Heineken Prize: the Dr H.P. Heineken Prize for Biochemistry and Biophysics. On this special anniversary edition, the jury has decided to nominate not one but two top scientists. In doing so, the jury honours not only the work of Aebersold and Mann, but also the field of proteomics. Previous laureates of the prize include Nobel laureate Carolyn Bertozzi (2022) and Bruce Stillman (2020).

Drivers of proteomics
Proteins are involved in all processes in the body. Without proteins, for example, there is no cell division, metabolism or growth. For a long time, it was thought that one protein performs one specific function. We now know that biology is much more complex. For example, it has become evident that one protein interacts with many different proteins to perform various functions. To understand how processes in our bodies work, it is not only necessary to identify proteins but also to uncover their interactions with each other. Large-scale research into this is called proteomics.

The jury believes that Ruedi Aebersold, professor emeritus at the ETH Zurich Technical University in Switzerland, and Matthias Mann, professor at the Max Planck Institute for Biochemistry in Germany, are drivers of this field. Their work has made essential contributions to identifying and analysing proteins and offered new insights into how they interact. Both scientists have developed new, innovative techniques that, among other things, have enabled accurate, quantitative measurements of thousands of proteins simultaneously, a method that has become a standard in the research field.

Although the two laureates have primarily followed their own paths over the past decades, they have significantly benefited from each other’s work. Moreover, they share a common goal: to identify the partnerships between all 8 billion proteins in a cell.

Applicability in medicine
As a result of the contributions of Aebersold and Mann, we better understand how healthy cells work and what goes wrong in disease. For example, we can now detect certain diseases early, such as liver disease. When someone is developing liver disease, the amounts of protein in the blood change. By detecting this early on, they can change their lifestyle and avoid becoming ill. Another important medical application is Mann’s research into allergic skin reactions to drugs. By studying patients’ affected skin cells, he discovered the cause and thus laid the foundation for treatment. He is currently analysing the differences in the interactions between proteins in cancer cells and normal cells within a single patient – an approach that could lead to personalised tumour treatments in the near future.

Key milestones over the years
Aebersold was among the first to recognize that our understanding of biological processes hinges not on genes but on proteins – the true workhorses of our cells. His advocacy for large-scale protein research was a testament to his visionary approach. He emphasized that a protein never operates in isolation, but is always part of a larger network, a concept that has since become a cornerstone of our understanding.

To understand how proteins work together, however, you must first know which proteins are present in the cell. One of the main techniques used to study this is mass spectrometry, which measures the masses of protein fragments. With this information, you can identify which protein you are dealing with. Mann was the first to develop an algorithm that could solve this puzzle. Thanks to this algorithm, many vital proteins were discovered. In doing so, Mann made a crucial contribution to analysing proteins in living systems. He did this with his supervisor and inspiration John Fenn, who received the Nobel Prize in chemistry in 2002.

Aebersold also made several essential technical contributions to mass spectrometry. For example, he made mass spectrometry suitable for a very targeted and accurate comparison of the protein composition of different cells. This enables the identification of the processes that are disrupted in a cell in disease. To apply this method optimally, Mann developed a mass spectrometer specifically for this technique. By joining forces, they created a method that almost everyone in the research field uses today.

About Ruedi Aebersold
Ruedi Aebersold (1954, Oberdiessbach) studied cellular biology at the University of Basel in Switzerland, where he also obtained a PhD in cellular biology. After two postdoctoral positions at the California Institute of Technology, he was appointed associate professor at the University of British Colombia in Vancouver in 1989. In 1993, he left for Seattle, where he was appointed professor of molecular biotechnology at the University of Washington in 1998. In 2000, he co-founded the world’s first Institute of Systems Biology there. In 2004, he moved back to Switzerland and became a professor of systems biology at the technical university ETH Zurich in Switzerland.

About Matthias Mann
Matthias Mann (1959, Thuine) studied physics and mathematics at the Georg August University in Germany. In 1988, he received his PhD in chemical engineering from Yale University in the United States. After a postdoctoral position at the Southern Danish University, he became group leader at the European Molecular Biology Laboratory in Heidelberg in 1992. In 1998, he was appointed professor of bioinformatics at the Southern Danish University, and he has been director of the Max-Planck Institute for Biochemistry in Martinsried since 2005. He has simultaneously been director of the proteomics programme at the University of Copenhagen since 2007.

Biochemists Ruedi Aebersold and Matthias Mann will be awarded the Dr H.P. Heineken Prize for Biochemistry and Biophysics 2024. The jury commends their pioneering work in proteomics, and especially their prolific and seminal contributions to new techniques to study proteins in a system-wide context. As a result of their achievements, we better understand how healthy cells work and what goes wrong in disease. Never before has the prize been awarded to two independent scientists.

In 2024, it will be 60 years since Alfred Heineken introduced the very first Heineken Prize: the Dr H.P. Heineken Prize for Biochemistry and Biophysics. On this special anniversary edition, the jury has decided to nominate not one but two top scientists. In doing so, the jury honours not only the work of Aebersold and Mann, but also the field of proteomics. Previous laureates of the prize include Nobel laureate Carolyn Bertozzi (2022) and Bruce Stillman (2020).

Drivers of proteomics
Proteins are involved in all processes in the body. Without proteins, for example, there is no cell division, metabolism or growth. For a long time, it was thought that one protein performs one specific function. We now know that biology is much more complex. For example, it has become evident that one protein interacts with many different proteins to perform various functions. To understand how processes in our bodies work, it is not only necessary to identify proteins but also to uncover their interactions with each other. Large-scale research into this is called proteomics.

The jury believes that Ruedi Aebersold, professor emeritus at the ETH Zurich Technical University in Switzerland, and Matthias Mann, professor at the Max Planck Institute for Biochemistry in Germany, are drivers of this field. Their work has made essential contributions to identifying and analysing proteins and offered new insights into how they interact. Both scientists have developed new, innovative techniques that, among other things, have enabled accurate, quantitative measurements of thousands of proteins simultaneously, a method that has become a standard in the research field.

Although the two laureates have primarily followed their own paths over the past decades, they have significantly benefited from each other’s work. Moreover, they share a common goal: to identify the partnerships between all 8 billion proteins in a cell.

Applicability in medicine
As a result of the contributions of Aebersold and Mann, we better understand how healthy cells work and what goes wrong in disease. For example, we can now detect certain diseases early, such as liver disease. When someone is developing liver disease, the amounts of protein in the blood change. By detecting this early on, they can change their lifestyle and avoid becoming ill. Another important medical application is Mann’s research into allergic skin reactions to drugs. By studying patients’ affected skin cells, he discovered the cause and thus laid the foundation for treatment. He is currently analysing the differences in the interactions between proteins in cancer cells and normal cells within a single patient – an approach that could lead to personalised tumour treatments in the near future.

Key milestones over the years
Aebersold was among the first to recognize that our understanding of biological processes hinges not on genes but on proteins – the true workhorses of our cells. His advocacy for large-scale protein research was a testament to his visionary approach. He emphasized that a protein never operates in isolation, but is always part of a larger network, a concept that has since become a cornerstone of our understanding.

To understand how proteins work together, however, you must first know which proteins are present in the cell. One of the main techniques used to study this is mass spectrometry, which measures the masses of protein fragments. With this information, you can identify which protein you are dealing with. Mann was the first to develop an algorithm that could solve this puzzle. Thanks to this algorithm, many vital proteins were discovered. In doing so, Mann made a crucial contribution to analysing proteins in living systems. He did this with his supervisor and inspiration John Fenn, who received the Nobel Prize in chemistry in 2002.

Aebersold also made several essential technical contributions to mass spectrometry. For example, he made mass spectrometry suitable for a very targeted and accurate comparison of the protein composition of different cells. This enables the identification of the processes that are disrupted in a cell in disease. To apply this method optimally, Mann developed a mass spectrometer specifically for this technique. By joining forces, they created a method that almost everyone in the research field uses today.

About Ruedi Aebersold
Ruedi Aebersold (1954, Oberdiessbach) studied cellular biology at the University of Basel in Switzerland, where he also obtained a PhD in cellular biology. After two postdoctoral positions at the California Institute of Technology, he was appointed associate professor at the University of British Colombia in Vancouver in 1989. In 1993, he left for Seattle, where he was appointed professor of molecular biotechnology at the University of Washington in 1998. In 2000, he co-founded the world’s first Institute of Systems Biology there. In 2004, he moved back to Switzerland and became a professor of systems biology at the technical university ETH Zurich in Switzerland.

About Matthias Mann
Matthias Mann (1959, Thuine) studied physics and mathematics at the Georg August University in Germany. In 1988, he received his PhD in chemical engineering from Yale University in the United States. After a postdoctoral position at the Southern Danish University, he became group leader at the European Molecular Biology Laboratory in Heidelberg in 1992. In 1998, he was appointed professor of bioinformatics at the Southern Danish University, and he has been director of the Max-Planck Institute for Biochemistry in Martinsried since 2005. He has simultaneously been director of the proteomics programme at the University of Copenhagen since 2007.

‘Your personality changes even when you are an adult’

For a long time, it was thought that our personalities are pretty much fixed from the age of 30. We now know that they can change throughout our lives. Manon van Scheppingen, a developmental psychologist at Tilburg University, studies what factors lead to personality change. She focuses particularly on young adults – people aged between 20 and 40.

‘Many young adults acquire a more mature personality over time, including more self-control and emotional stability,’ says Van Scheppingen. ‘But it is not yet clear what causes these changes. I therefore explore whether specific life transitions can explain this. For example, I expected the transition to parenthood to be one of the factors.’

Van Scheppingen had people who had their first child fill in a questionnaire about their personality at different times. She compared the results with a control group. ‘People who had a child did not, on average, appear to develop a more mature personality during that period than people who did not have a child.’ She did notice that some new parents, especially mothers, temporarily had lower self-confidence.

Although, on average, Van Scheppingen did not see a major personality change due to parenthood, some people do change significantly because of it. ‘For example, some people gain much more self-confidence, others much less,’ says Van Scheppingen. ‘In the near future, I will be studying what factors could explain these differences. In addition to the first child, I will also examine two other life events: the first job and cohabitation. Besides pre- and post-measurements of their personality, I will also explore how people experienced these events: did they perceive them as positive or negative? How was their stress level? That way, I hope to find out why some people change more than others.’

Van Scheppingen has also studied the role personalities play in romantic relationships. ‘We often hear that opposites attract. But our research found that people tend to select a partner who has similar personality traits, including a similar level of self-control.’

‘My research is quite fundamental,’ says Van Scheppingen. ‘But if we better understand how and why people change, this could help develop therapies in the field of personality change. However, I think we should also celebrate the fact that everyone has a different personality. I hope that my research can ensure that people get a better understanding of their personality and can organise their lives in the way that best suits it.’

‘Flowers Adapt Evolutionarily to Their Pollinators’

Plants need pollinators for reproduction, and they attract these pollinators with colourful flowers. Casper van der Kooi, an evolutionary biophysicist at the University of Groningen, studies how these colours form and evolve.

‘The colour and brightness of flowers change through evolution to be optimally visible to the pollinator,’ says Van der Kooi. Not all pollinators can see all colours equally well. Many insects, for example, cannot see red. As a result, flowers that rely on insects for pollination are rarely red. Many red flowers rely on birds, which can see red well, for their pollination. ‘The poppy is an exception, but it “cheats” because it also reflects ultraviolet,’ explains Van der Kooi. ‘Insects can see that very well.’

Van der Kooi showed that the colour of a flower is not only determined by its pigment, but that the internal structure of the flower is equally important. ‘A yellow flower, for example, has a pigment that absorbs blue light and reflects the rest,’ he says. ‘As a result, we see the remainder of the spectrum as yellow. But the way in which the flower reflects that remaining light is also important. A flower consists of several layers of cells, which scatter light in different ways. I study how this cell structure leads to the visual signal that animals and humans see.’ An example of a flower with an exceptional structure is the buttercup. ‘It has an outer layer that makes it very shiny.’

Lately, Van der Kooi has also been focusing on butterflies. He studies how the colours of their wings form and evolve to best attract a mate. ‘What makes butterflies so fascinating is that they have the most brilliant colours found in nature. They are also very dynamic – they fly around each other, continuously reflecting light in different ways. We want to study how butterflies’ colours combined with their behaviour determine how attractive they look to a potential partner.’

Van der Kooi’s research helps to better understand communication between animals, as well as between plants and animals. ‘Colour is a wonderful way to visualise biodiversity. I hope to make the abstract concept of biodiversity more concrete with my research and thereby inspire others to get involved in protecting plants and animals.’

‘Reconciliation between countries often requires uncomfortable compromises’

Historical research on international relations often focuses on wars and conflicts. Instead, Lorena De Vita, a historian at Utrecht University, focuses on how countries can reconcile afterwards. ‘I want to know how people and countries deal with the aftermath of horrors such as wars and genocides,’ says De Vita. ‘In addition, I am exploring what we can learn from this for the present.’

De Vita aims to discover what the conditions for reconciliation are, why it has succeeded in some cases and not in others, and who the protagonists are. In doing so, she looks beyond obvious individuals such as prime ministers and foreign ministers. ‘Of course, I did a lot of research in the official archives of ministries. But I also try to look at people who do not usually end up in the history books. In some cases, among the real diplomats there also turned out to be scientists, lawyers, and journalists.’

Among other things, Vita studied how Germany and Israel reconciled after World War II. ‘An important lesson I learned is that such a reconciliation is full of uncomfortable compromises. One of the reasons why the reconciliation finally succeeded is that there were concrete interests on both sides. For Germany, it was important to show other countries that it was taking responsibility for the past. It did so partly by negotiating reparations to Israel. And Israel was in a dire situation in the early 1950s – almost on the brink of economic collapse and politically extremely isolated in the Middle East. Also important was that there were enough people who felt it was worth pursuing dialogue. Not just at the highest level: there were also groups of citizens from both sides restarting the dialogue.’

In addition to reconciliation between countries, De Vita studies other forms of reparations. ‘Today, there is still a strong call to “repair” various events in history, such as slavery, colonialism, and genocide,’ says De Vita. She is currently researching what this ‘repair’ might look like, including by studying the diaries of German lawyer Otto Küster. He negotiated reparations for Holocaust survivors after World War II. ‘I am analysing these unique historical sources in the hope that this will help us better understand the ways in which you can right past injustices.’

‘Efficient lung cancer screening can prevent deaths’

Early detection of cancer can offer many health benefits. If a tumour has not yet metastasised, it can often still be removed or treated. However, it is not feasible to screen everyone continuously. That is why Kevin ten Haaf, an econometrician at Erasmus MC Rotterdam, is developing models to determine how to personalise screening programmes. He focuses specifically on lung cancer.

‘We want to identify who is at high risk of developing lung cancer,’ says Ten Haaf. ‘Using smoking history and age, we can already determine about 90 per cent of the risk. Important factors also include whether people have COPD and whether lung cancer runs in the family.’ It is important to screen high-risk individuals, while for low-risk individuals, the benefits sometimes do not outweigh the drawbacks, including the pressure this creates on healthcare. For example, screening might detect a tumour in someone of old age or with a limited life expectancy that would not have caused problems in their lifetime. ‘It is better to stop screening at some point.’

Ten Haaf’s research underpinned several screening programmes and recommendations, including those in Australia, Switzerland, the United States, and the province of Ontario in Canada. Currently, his research focuses on several European countries, including the Netherlands. ‘When developing a screening programme, we first map smoking behaviour in a country,’ says Ten Haaf. ‘With this, we calculate how many people are at high risk of developing lung cancer. We then compute thousands of strategies, evaluating different combinations of start and stop ages, time between screenings and risk levels. Suppose you scan this group of people every year from age 55 onwards: how many CT scans would you need? What would that cost? How many people would no longer die of lung cancer? And how long would they live after their cancer deaths are prevented?’ Using these scenarios, Ten Haaf determines the optimal strategy for a given country.

Screening programmes can help reduce deaths from lung cancer, but Ten Haaf stresses that preventing people from smoking and helping people to quit remains key. This helps prevent not only lung cancer but also other diseases. And if a person has already developed lung cancer, quitting smoking ensures that treatments are more effective.

In the future, Ten Haaf plans to also apply his knowledge to screening and treatment of other diseases, such as breast cancer, head and neck cancer, bladder cancer, and cardiovascular disease. ‘I hope to contribute to personalising screening and treatments in as many diseases as possible. That way, we can use the doctors and resources we have to help as many people as possible.’