Stefan Rüdiger appointed as Professor of Protein Chemistry of Disease
Research group develops novel strategies to target incurable diseases
Utrecht University has appointed Stefan Rüdiger as Professor of Protein Chemistry of Disease. Chemist Rüdiger and his group aim to tackle diseases that are caused by protein misfolding, such as Alzheimer’s disease and Huntington’s disease. They focus on how chaperones, proteins that aid other proteins to fold into their proper shape, control protein quality. Using this knowledge, they want to develop drugs and treatment strategies that prevent the negative consequences of protein misfolding at the earliest stage.
Proteins are molecular machines that run all vital processes in our cells, such as the metabolism, DNA replication or the transportation of molecules. For proteins to function properly, they first need to fold into their correct three-dimensional shape. If they fail to do so, proteins might disfunction or even become toxic. Also, misfolded proteins might interact with each other and form aggregates, which can also become toxic. Protein aggregates in the brain are associated with several fatal diseases, such as Alzheimer’s disease or Huntington’s disease.
Mimic protein machines
Chaperones are “protein machines“ that help other proteins to fold into their native shape. In doing so, they help to control protein quality and to prevent the aggregation of misfolded proteins. Rüdiger: “We are trying to understand how these machines work at the molecular level. We want to use this knowledge to develop small compounds that mimic these natural machines, so that we can target these aggregates at the earliest stage possible.”
Diseases like Alzheimer’s and Huntington’s usually start later in life. In most people, protein quality control works properly when they are born. Rüdiger: “Why do we lose control over the fate of our proteins when we get older? Actually, it is amazing how little we know. We do not even know why the aggregates are toxic.”
Being a pessimist and a scientist would not go together very well.
Yet, Rüdiger also emphasizes that a lot of progress has been made in the research area. Rüdiger: “Some milestones have been reached in recent years. Progress has been made in the understanding of the molecular shape of the aggregates, and of the mechanisms behind the functioning of chaperones. We do now know how proteins and protein aggregates look. My group is able to purify these aggregates out of patients’ brains and do biochemistry with it. This means that we can work with the real target. And we now have highly sensitive techniques that allow us to study these aggregates.”
Work by Stefan Rüdiger (acryl on hardboard). Rüdiger: “Our fate is enshrined in our ability to control diseases. In Greek mythology, three Moirai were working on the thread of life, determining our fate to better or worse. Our work is dedicated to breaking this frame by finding molecular solutions to regain control of the processes that determine our fate.”
The right time
According to Rüdiger, the time is right to go from understanding how the chaperones work, to applying that knowledge to the source of the problem. Rüdiger: “Ultimately, our goal is to cure these diseases. We are working on the first step, trying to develop compounds that target protein aggregates and make them disappear. But once you have a compound that works in the lab, the next step would be to make it work in a real-life situation. This is challenging and will only be solved based on sufficient molecular understanding. The compound has to go into the brain, where it has to find and destroy the target, without causing serious side effects. This is very ambitious. Statistically, the chances of dying of Alzheimer’s during your research career are higher than the chances of developing a cure.” Despite these odds, Rüdiger is optimistic. Rüdiger: “Being a pessimist and a scientist would not go together very well.”
Rüdiger has led his research group in Utrecht since 2004. According to the researcher, his appointment as professor will increase the visibility of the research done in his team. Rüdiger: “Funding for research on diseases is usually given to medical centers. This chair makes it explicit that work done at Utrecht University’s Department of Chemistry has a big impact on finding cures for diseases.”