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 machinesChaperones 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."
ProgressDiseases 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.
Prof. Stefan Rüdiger
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."