Sergey B. Zotchev: Learning from nature

Nature knows best: Molecular genetisist Sergey B. Zotchev isolates microorganisms from nature to find those that could potentially be used in the development of new drugs. uni:view talked to him about genetic engineering, the development of antibiotics and about being a movie director in another life.

60 percent of the drugs on the market today are derived from or inspired by natural products. This sounds like a lot? Not according to Sergey B. Zotchev, who has been head of the research group on Pharmaceutical Biotechnology at the University of Vienna since September 2015: "Some of the microbes in nature produce compounds that bind to a particular molecule in other living organisms (target) – and this is exactly what drugs do to have an effect on disease-causing bacteria or cancer."

Inspired by nature

Sergey B. Zotchev's major field of expertise is molecular genetics of bacteria, with a focus on genetics and the biochemistry of antibiotic biosynthesis. Discovering new natural products and trying to developing new medications based on them is his daily business: "Various types of microbes can produce biologically active compounds – to communicate, to fight other microorganisms or even bigger organisms. We try to identify these compounds and use them for our purposes", explains Zotchev.

In order to find microbes that could potentially be used in the development of drugs, Zotchev and his team are isolating organisms from the ocean sediments, marine sponges and plants. Recently, they have been targeting Leontopodium alpinum, better known as Edelweiss. They had a permit to collect the protected mountain flower in the Austrian Alps and have so far isolated more than one thousand microorganisms from it.

"Some chemistry needs to be done"

"Since we are living in the genomic era, we also look at the genomes of the microorganisms producing natural products", says Zotchev. What he often discovers are so-called "silent" genes: They are only active in nature in certain conditions, but not in the lab. "They need a signal from the environment in order to produce a certain compound. We are trying to imitate these signals to activate them forcefully by using various chemicals or genetic engineering."

Actually, only a small number of natural products can be used as drugs in their original form. In most cases, these compounds have to be modified using chemistry or genetics – to be, for example, less toxic or more soluble. "Some chemistry always needs to be done", knows Zotchev.

Nystatin revisited

In 1950, Nyststin – an antibiotic to treat fungal skin infections – was discovered. Zotchev and his team reinvestigated the drug by applying biosynthetic engineering: they found the genes that are responsible for the biosynthesis of this antibiotic, manipulated them – and created a new drug. The antibiotic "revisited" turned out to be much better than many known anti-fungal antibiotics, and is now in the clinical development process.

How it all started …

Zotchev's interest in biology started in secondary school thanks to an excellent biology teacher from Moscow State University. "I fell in love with the subject", remembers Zotchev. He followed the path of microbes and bacteria, got a master’s degree in microbiology and a PhD in molecular genetics at the State Scientific Center for Biotechnology NIIGenetika in Moscow.

Sergey B. Zotchev taking a walk along the shores of a fjord during his time in Trondheim, Norway. (Photo: privat)

Driven by personal interest

He was, among other things, a postdoc fellow at the Department of Molecular Genetics in Osnabrück, at the School of Pharmacy in Wisconsin and at the Karolinska Institute in Sweden and held a faculty position (first as associate professor, then as full professor) at the Department of Biotechnology at the NTNU in Norway. "The path of researchers is quite uncertain and you need to move around a lot. What always pushed me was my personal interest, the satisfaction of my own curiosity", says Zotchev.

His personal interest brought him all the way to the University of Vienna. Since September 2015 he conducts research and teaches at the Department of Pharmacognosy: "Here I am part of a large Pharmacy Center. I work with excellent people from different fields, with different expertise – I find that this complements my research."

… in another life

He loves his job as Professor in Pharmaceutical Biotechnology, but he also gets excited when it comes to travelling, architecture and film. "I watch quite a lot of movies. Sometimes I cannot help it and I am disappointed: The script is good, the actors are good, but the direction is not. I would make it differently and it would be a great hit, but well … maybe in another life", smiles Zotchev. (hm)

Sergey B. Zotchev's inaugural lecture "New Drugs from Good Bugs, and How to Find Them" will take place on 9 June 2017 at 17:00 at the Small Ceremonial Chamber (Kleiner Festsaal), University of Vienna, Universitätsring 1.