Franz-Ulrich Hartl: Illuminating the role of the chaperone of the proteins

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Franz Ulrich Hartl is the director of the Department for Cellular Biochemistry at the Max-Planck Institute for Biochemistry in Martinsried. Quelle: MPI for Biochemistry, Martinsried

31.03.2006  - 

For Franz Ulrich Hartl, butterflies and single-celled organisms were already a subject of great fascination as a child. Hours were spent dissecting these wonders, or examining them under a microscope. Today, Hartl is the director of the Department for Cellular Biochemistry at the Max-Planck Institute for Biochemistry in Martinsried and is an expert in the world of proteins. The 49-year old has breathed life into a fundamental mystery: How the long-chain molecules in the cell, which are essential for the body, actually assemble themselves into their three-dimensional form, in order to become active. Now, he has been distinguished for this discovery with the 2006 Körber European Science Award, worth 750,000 Euros.

Proteins are the body's molecular workhorses - no human could survive without them. Ever since scientists found out that there are far more proteins than genes, the importance and function of these many molecules has been the subject of intense scrutiny. Researchers such as Hartl hope to understand, in detail, how the lined-up molecular components become three-dimensional, and thus an active protein molecule. In specialized jargon this process is called protein folding and Hartl discovered early on in his career that a special sort of protein molecules - the chaperones - play a crucial role. "Chaperones are a kind of molecular accompaniment, which ensure that the long protein chains fold themselves up, and ultimately end up with the right sort of structure". So describes Hartl the research field to which he has been dedicated for decades.

From medicine to biochemistry

As a child in Essen, Hartl was already extremely enthusiastic about science. At 13 years of age his biology teacher taught to him how to collect insects and map them into their various biotopes. "I was inspired by this, and went into the forests again and again to find new insects ", remembers Hartl. Soon, it was clear that his later occupation would lie somewhere between biology and chemistry. Following his Abitur, the German high-school diploma, Hartl nevertheless decided to begin studying medicine in Heidelberg. "I did not want to commit myself exclusively to biochemistry, and at that time it was also simpler to take up the biochemical courses within the medicine studies", says Hartl. It was at that time that he first came into contact with the analysis of enzymes and cell organisms, in the laboratory of William Just, and from then on his future path was clear. After his graduation in Heidelberg, which he completed with summa cum laude, Hartl went into the laboratory of Walter Neupert at the Institute for Physiological Chemistry of the University of Munich, where he ultimately began his intensive work on the folding of proteins.

At the beginning it was only clear that folding is an elementary process, without which proteins would not be able to become active. It was also known that increased numbers of chaperones are formed with rises in temperature - a response by the cell to the stress situation. In the meantime, Hartl has uncovered how the folding process takes place in detail: In a first step, the unfolded protein chain is stabilized by the chaperone, in order to prevent knotting. In a second step this protein complex connects itself to a chaperone, which then initiates and converts the correct folding. Again, this is not merely achieved via a simple attachment. "Certain chaperones form a kind of cage, into which the protein chains to be folded are locked up", explains Hartl. In this reduced area the molecules have clearly no other choice than to fold in the correct way. For his innovative work in this area, Hartl has already been distinguished several times over: he received the Leibniz Prize from the German Research Council (DFG) in 2002, and won the 2006 Körber European Science Award, worth a cool 750,000 Euros.

Career leads ultimately to the ‘Holy Grail of biochemistry’

When the scientist looks back on his career development, above all, he is glad to have met the right people. "I am very grateful to Walter Neupert because, thanks to him, I was able to lead a working group at a young age and, through this, to make great progress," says Hartl today. Back then, the foundations were laid for an impressive career: Following his postdoctoral lecture qualification in Munich, Hartl went to the Sloan Kettering Institute in New York at the beginning of the 90's. Before this move, he had also received offers from Harvard, Berkeley and Princeton. "To be honest, I could have happily remained in the USA, but then in 1997, out of the blue, came the offer from the MPI for Biochemistry in Martinsried to lead my own new department - and I could not turn that down". Ultimately, the MPI had already fascinated him back in his doctoral and post doctoral days: "As a biochemist, it was the Holy Grail."

Using chaperones for drugs

Together with his wife, who likewise works as a biochemist, he finally returned to Germany. In the meantime, he has not limited himself purely to basic research. At the moment, the focus is on the role that chaperones could play in the development of new medicines. "With many neurodegenerative diseases such as Alzheimer’s or Chorea Huntington, disrupted protein folding plays a crucial role, possibly because the activity of chaperones in old age generally dies out or the chaperoness which allow for proper folding are missing in those patients". If it were possible to purposefully intervene in this process – using some sort of drugs that increase the quantity of the chaperones in a specific area - then the folding could possibly be improved and controlled. Working together with the scientist Erich Wanker at the Max-Delbrueck Center for Molecular Medicine in Berlin, Hartl has identified such a drug candidate for Chorea Huntington, which could be used to prevent the knotting of protein molecules in the brain.

Passionate collector of red wine

As a colleague, Hartl tries to organize the work with as little hierarchy as possible, and to always have an open ear as a boss. "Science requires a high level of self motivation, therefore the atmosphere must be right, otherwise you’re just not productive". Of this, he is convinced. During critical discussions, however, it’s not only his direct teammates taking part, but also his wife. "Colleagues are somewhat restrained when being critical of the man at the top," he says “but she’s certainly not shy about opening her mouth”. In this way, some evenings end with a scientific discussion, preferably with a nice glass of red wine. Hartl shares this preference with his wife, and both have developed a passion for collecting wine, which has already resulted in a substantial wine cellar. Another hobby however - making music with flute and piano – had to be put on the back burner for science. "It’s still fun for me to sit at the piano, but when faced with a Bach fugue, for example, I’m definitely made aware of the limits of my capabilities."