Section: Science Life
Laboratory visit |
“Now it’s a question of the details”
Teresa Fitzpatrick and her group at the Institute of Plant Sciences study how organisms produce vitamins. In the case of Vitamin B6 she has succeeded in making important breakthroughs in the last few years. Now she wants to understand the synthesis of this vital substance in even more detail.
Thomas Raschle smiles as he talks about his work and explains that “In the last three years I have spent about 80 percent of my working time in this laboratory.” He has almost completed his thesis – the examination takes place in the week beginning 26 March 2007. Using flasks and dishes, forceps and pipettes still fascinates him. He says “I enjoy working here. I have a great degree of independence and can also decide and try out many things by myself.” One reason for his happiness might be that his work has enabled him to contribute something to the success of the working group.
Thomas Raschle is one of Teresa Fitzpatrick’s doctoral students. Irish by birth, she has led a group of six young scientists at the Institute of Plant Sciences for the past four years. (1) Teresa Fitzpatrick’s main interest is currently Vitamin B6 (2), a substance on which all living organisms are vitally dependent, although by no means all of them can also produce it themselves. Animals and humans must obtain the vitamin to satisfy their needs through diet.
The model as an exception
For a long time people thought they understood how organisms produce vitamin B6 because it was possible to reconstruct the individual steps in detail for the model organism E. coli. A total of seven proteins are involved in the synthesis in this bacterium. It was all the more astonishing when Teresa Fitzpatrick showed a few years ago that a completely different and considerably simpler mechanism exists in plants. “E. coli turned out to be an exception. In fact the synthesis involves just two proteins, PDX1 and PDX2, in most of the other organisms that produce vitamin B6.”
When she first solved the structure of PDX1 and PDX2 with the help of German scientists at the University of Heidelberg she was slightly disappointed at seeing the results because the two proteins have a well-known basic shape that did not promise anything very spectacular. However, as the studies progressed it became apparent that the structure really did contain something. “Vitamin B6 is formed when PDX1 and PDX2 dock on one another.” Teresa Fitzpatrick holds up a three-dimensional model shaped like a double gearwheel to explain the process. She points to the inner part: “First of all PDX1 forms two hexagons arranged one on top of the other. Then the PDX2 molecules dock onto their outer surfaces. We have clear evidence that the ammonia which is the decisive factor in the synthesis can then reach the interior of the two rings through a channel.”
Chance as a helper
In the last few years the group has worked hard to characterise the interaction of the two proteins as exact as possible. Thomas Raschle explains that “Chance gave us a helping hand again and again. We suddenly discovered unexpected routes that carried us forward.” For example one decisive question is exactly which amino-acids in the two proteins are involved when they dock onto each other. Thomas Raschle explains the diagram on his computer screen: “I selectively blocked individual amino-acids and then looked to see how that affected the production of B6.”
As a layman looking at the graphics Teresa Fitzpatrick had compiled in a PowerPoint presentation for a conference, one gains the impression that the mechanism has now been fully solved. However, Teresa Fitzpatrick thinks she has still not reached her destination. In the near future she wants to know in even greater detail exactly what takes place when PDX1 and PDX2 come together. She thinks that “On the whole we understand what happens in the cells, but now it’s a question of the details, which are important not only for fundamental research.” In the context of a project funded by the EU, Teresa Fitzpatrick together with scientists from Heidelberg, Graz and Glasgow hope to find a starting point in the fight against malaria. She says that “The malaria pathogen also produces vitamin B6 using the mechanism we have discovered. Perhaps we can find a point in the reaction chain where the synthesis of this vital substance could be blocked.”
"Looking back over the last few years, the researcher says “The project really ran very well. There is enormous competition in this research field, but the pressure is also stimulating – most of all when one is in the lead!” She is also facing a personal radical change in the near future. The retirement of “her” Professor Nikolaus Amrhein due to age is a watershed moment for her. She explains that “Three doctoral students are currently finishing their studies with me at the same time. There is no question of employing new staff, because I myself must also look around for a new post. At any rate two of my doctoral students can continue working here for a few more months
Transport is also important
Immediately opposite to Thomas Raschle, Lukas Bürkle bends over the laboratory bench. German by birth, he has sown the model plant mouse-ear cress (Arabidopsis thaliana) in a dish and allowed it to germinate. Now he pulls the young seedlings out of the earth with forceps and freezes them in liquid nitrogen. In contrast to Thomas Raschle, who works on the production of vitamin B6 in bacteria, Lukas Bürkle’s work today involves a different vitamin. The scientist explains that “Later I am going to crush the plants in a mortar, digest them and extract the DNA from them.” Lukas Bürkle hopes this will give him information about how vitamin B1 is synthesized in the plant. He counters a related question by saying there is no reason to expect ground-breaking insights like those in the case of vitamin B6. “The corresponding reaction steps in E. coli are known, and we think we are sure that a similar process takes place in plants.” However, he is convinced that confirmation would in itself be an important discovery for the science.
Lukas Bürkle has been a post-doctoral student in Teresa Fitzpatrick’s group for eighteen months. He finds that working with vitamins is an extremely fascinating activity. He explains that “Finding out how these vital substances are produced is exciting. However, I want to understand not only more about their synthesis but also how vitamins are distributed afterwards and transported in plants.” He is now working on exactly this subject in a second project which he began a short time ago. He thinks that “In any event there is no lack of unsolved questions.”
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