27 May 2014 - A DISCOURSE: LEONARD KAYSSER AND TIMO NIEDERMEYER
Two Approaches – One Goal
One of them speaks of “treasures, waiting to be found” while the other focuses on new “compounds”, but both Timo Niedermeyer and Leonard Kaysser mean the same thing and have a mutual goal: As recently appointed assistant professors at the DZIF Thematic Translational Unit (TTU) “Novel Anti-infectives”, they both want to discover new natural agents against bacteria, viruses and fungi. Both researchers have been working for the DZIF at the University of Tübingen since November 2013.
Timo Niedermeyer works in the field of microbiology/biotechnology on the topic of “actinobacterial anti-infective compounds” and Leonard Kaysser is in the field of pharmaceutical biology working on the topic “synthetic biology of anti-infective agents”. Their workplaces in Tübingen are located near each other, and so it is no wonder that after a short time they decided to join forces to work for their common cause. “I am the pharmacist in biology; Leo is the biologist in pharmacy,” Timo explains, “And we need expertise from both to discover new active agents and develop them further.”
Both researchers concentrate their search for novel anti-infectives on natural agents, because most of the effective drugs currently available against infectious diseases are produced by bacteria or fungi. Nature has a lot of potential which certainly has not yet been fully exploited, mainly due to high costs and efforts required. This is why the pharmaceutical industry has largely withdrawn from conducting screenings. Here, the DZIF’s task is to try and bridge this gap and find, isolate and investigate new active agents.
For a long time, Tübingen has been focusing on a group of bacteria which has often delivered interesting agents: The actinomycetes group. Timo Niedermeyer will initially also concentrate his research on this group, cultivating strains and screening extracts for active agents and also deciphering the structures of novel substances. “Some believe that that there are no more gains to be made with this method,” Timo says with a grin and immediately adds: “I am of a completely different opinion here.” And the pharmacist is certain that actinomycetes have not yet been fully exploited. Tübingen has accumulated a historical collection of about 600 substances available for anti-infective agent screening. “This is also a treasure waiting to be found.”
The Pharmacist in Biology
Timo Niedermeyer has had an interest in natural products since early on. “I am interested in plants—in what nature can produce, be it medicinal or poisonous.” For a short period of time, he struggled with his decision of whether to pursue his scientific interests or his love of music. Then he decided: he studied pharmacy in Berlin and made music his passion and a successful hobby: Timo Niedermeyer now plays many instruments.
After his practical PhD in Greifswald from 2002 to 2004, he worked at Riemser Arzneimittel AG in the field of “Chemistry, Manufacturing and Controls” for a few years, and then moved to Cyano Biotech GmbH in Berlin in 2008 as “Head of Natural Product Research and Development”. There, he was responsible for the entire process for the last few years, from screening and isolation to deciphering molecular structures all the way to pre-clinical trials. The call for his professorship came at a good point in time, as he had been already been considering becoming a professor for a quite a while. Moving from Greifswald to Berlin and then on to Tübingen in southern Germany for this was not a problem for him. However, he still commutes, because “Moving with my wife and four children will take a bit longer.”
The Biologist in Pharmacy
Things were a little easier for Leonard Kaysser, who prefers just being called Leo. His wife and his eight month old baby had to come along with him, because San Diego in California, where he had been doing research on marine natural product chemistry and biosynthesis for the last three years, would simply have been too far away to commute. Leonard Kaysser’s stops in his career path have a globetrotter feel to them: Stuttgart – Zurich – Stuttgart – Sydney – Tübingen – San Diego – Tübingen…, but in reality he is very attached to his home region, he says. In the end, his scientific interest always dictated to where he had to move. This was also true for his last stop in California, where Leo learnt and applied the latest research methods at Professor B. S. Moore’s laboratory. Professor Moore is a pioneer in marine natural product research.
Leonard Kaysser’s career path began with his studies of technical biology in Stuttgart, where he started concentrating on microbial biotechnology and natural products. “How can living organisms produce such complex chemical substances?” This question has fascinated him from the start. After a research stay at the Swiss Federal Institute of Technology Zurich (ETH), he completed his diploma thesis at the University of Stuttgart. Subsequently, he went to Sydney, Australia for half a year where he investigated pathogenic bacteria and quality control. Occasionally, when time permitted, he went diving—a hobby which is now difficult to pursue in Tübingen. “But I don’t have enough time for it anyway, and since I have become a father, I have discovered a new hobby: sleeping,” he says.
Tübingen is “homeland” for the assistant professor. He completed his PhD there, in which he investigated the biosynthesis of bacterial secondary metabolites. He discovered the first gene cluster for antibiotic biosynthesis, and gained knowledge and experience in the biosynthesis of natural products as well as in molecular biology. Gene clusters are groups of genes which usually code for a specific metabolic pathway and are located close to each other on the genome.
From Gene Cluster to Novel Substance
Leonard Kaysser assumes that most actinomycetes could produce 10 to 30 times more natural products than we currently know about today. He would like to identify this potential wealth of new biosynthesis pathways by means of gene clusters. Once he has found interesting gene clusters, he will clone them in other bacteria and hopefully generate new substances in this way. “And this is where Timo becomes important again, because he can isolate substances and decipher structures.”
Natural Compound Libraries
The DZIF not only offers the young researchers a network of experts but also an extensive “Natural Compound Library” which has been built up by DZIF members and is available to all for screening campaigns. It already contains several hundred pure products and several thousand extracts from natural sources. Together with the 600 substances in Tübingen, the two professors certainly have enough work waiting for them. And besides this—Timo would also like to further investigate blue-green algae. “I have gained a lot of know-how in this over the last years and am sure that active agents can also be found in cyanobacteria. It would be a pity to waste this potential.”
During the subsequent photography shooting, the two quickly become engrossed in conversation: They talk about children and finding names for them, about how men gain weight during pregnancy and about other important things that count in the lives of two young successful researchers. And they do not lose sight of their goal: “We have to find new compounds,” Leo Kaysser says. “That is what it boils down to and what our performance will be measured by”.