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Kerstin Otte and her specific interest in tiny RNA molecules

Molecular biologist Kerstin Otte is guided and inspired by content. “I like to do things I find exciting, whether they fit into my CV or not. This is not the key issue for me.”

This interest-based principle has brought Kerstin Otte to the Upper Swabian city of Biberach where she has found her professional niche. She has been professor of general, molecular and cell biology at the Faculty of Pharmaceutical Biotechnology at Biberach University of Applied Sciences since 2006. She is currently specifically focussed on a class of small RNA molecules that gives her immense pleasure and has already brought her in contact with Nobel laureates and government ministers.

The time is ripe for research

Prof. Kerstin Otte is the head of the Institute of Applied Biotechnology. © Biberach University of Applied Sciences

Otte has been the head of the Institute of Applied Biotechnology (IAB) at Biberach University of Applied Biosciences since 2006. “After years of development, the IAB is gradually taking shape,” said Otte with confidence. In 2012, the institute acquired more than one million euros in third-party funding and now has 14 professors, numerous doctoral students taking part in a cooperative doctoral programme, a BMBF-sponsored programme and others, master’s and bachelor’s students and a laboratory manager – all of them carrying out applied research along the entire biopharmaceutical value creation chain. 

The IAB also carries out basic research, a domain that is usually the realm of universities and other research institutions rather than universities of applied sciences, just as universities also reserve the right to train doctoral students. Kerstin Otte is well aware that her and her colleagues’ insistence on carrying out basic research is leading in some ways to a cultural change. Nevertheless, scientists from Ulm University, which is only a stone’s throw from Biberach, find it quite natural to work with their Biberach colleagues. The cooperation between the Ulm and Biberach researchers, which was initiated in 2006 with the establishment of the Pharmaceutical Biotechnology master’s course, appears to be developing into a lasting alliance.

Presentation of the miRNA project to Nobel laureates in Lindau

The invitation to participate in the 63rd Lindau Nobel Laureate Meeting in summer 2013 was like an academic accolade for Kerstin Otte, who, together with her PhD student Simon Fischer and the IAB’s laboratory manager, gathered with over 30 Nobel Laureates and 600 graduate and undergraduate scientists from almost 80 countries. They also had the opportunity to talk with a Baden-Württemberg minister. Kerstin Otte and her colleagues were invited to present their innovative research approach related to microRNA (miRNA) molecules.

Kerstin Otte decided to focus on miRNA when she began working at Biberach University of Applied Sciences, thus fulfilling her most heartfelt wish. She had closely followed the development of the Human Genome Project from her early biology studies and was specifically attracted by the tiny snippets of the genome that were long dismissed as “evolutionary junk” because they were transcribed from DNA sections that do not carry information for making proteins.

These miRNA molecules are around 21 or so nucleotides long and were discovered in the threadworm Caenorhabditis elegans in the laboratories of Gary Ruvkuns and Victor Ambros in 1993. It was long thought that these regulatory biomolecules were only found in C. elegant, which is why they were not recognised as a distinct class of small RNAs. This only changed in 2001 when the molecules were found in both eukaryotes and prokaryotes.

The new idea: using miRNA as research tools

The IAB researchers’ idea of using miRNA to optimise production cells is very work intensive. © Otte, Biberach University of Applied Sciences

MicroRNAs are ubiquitous, encoded by normal genes, transcribed in the nucleus and cut into tiny snippets by enzyme complexes. A single miRNA molecule can regulate up to one hundred genes in the cytoplasm by binding to mRNA, thereby preventing the biosynthesis of proteins. Many researchers use this property for exploring the use of miRNAs in the treatment of tumours, not so Kertin Otte who is pursuing the idea of using miRNAs as tools for augmenting the productivity of cells. It goes without saying that this idea fits well into a region which is a hotspot of biopharmaceutical production.

Her PhD student, Simon Fischer, used Chinese hamster ovary (CHO) cells as host cell lines to identify mouse miRNA molecules capable of increasing productivity, cell growth and apoptotic capacity. The researchers will now stably integrate these miRNA molecules into the genome of the CHO cells using plasmid vectors with the goal to increase the number of miRNA molecules in the CHO cells. CHO cell lines are regarded as the biopharmaceutical industry’s workhorses for therapeutic protein production. The genome of the Chinese hamster was sequenced in 2011.

The molecular mechanism of miRNAs first has to be deciphered and understood in detail before the miRNAs can be used as ‘biopharmaceutical production assistants’ in the highly regulated world of pharmaceutical production. This is basic research par excellence and is very work intensive. The researchers from Biberach only have a few international competitors. “Our current data suggest that we have enough work for the next 20 years or so,” Otte said, visibly pleased. The first comprehensive screen has led to the identification of many interesting miRNA candidates, including miRNAs that induce apoptosis. These are suitable for tumour research and might already broaden the research field at this early stage.

Otte assumes that she will eventually end up screening human cell lines for miRNAs as she cannot foresee spending all her research life on a particular cell or gene. As mentioned earlier, this once again shows that her academic vita does not follow a specific line, but that she loves variety.

Lost her heart to molecular biology in California

Small double-stranded RNA molecules (red) in CHO cells. GFP reveals the cytoskeleton in green; the nuclei are stained blue. © Otte, Biberach University of Applied Sciences

Kerstin Otte began her scientific career as a biology student at the University of Marburg in 1986. She interrupted her studies in 1989 to spend 12 months in the USA doing a biochemistry bachelor’s degree at one of the well-known east coast colleges and an internship in a San Diego company (she still has the company mug on her desk) where she discovered her passion for molecular biology. On her return to Marburg in 1990, Otte decided to change from botany and animal physiology to molecular biology. She completed her degree thesis on the isolation and characterisation of an insect gene in 1993 and started looking for European universities where she could do her PhD. 

She chose Uppsala, a university with many ancient traditions, where she completed her PhD on insulin-like growth factors in cell culture in 1997. Meanwhile, many papers had been published on imprinting, which hugely fascinated Otte due to the fact that ‘her’ gene was also subject to parental genomic imprinting (ed. note: epigenetic process that leads to monoallelic gene expression). This emerging interest also meant she needed to find a new supervisor, which she found in a professor at the Wellcome - CRC Institute in Cambridge, UK. She spent two years exploring the phenomenon on genomic imprinting in the mouse model before returning to Germany at the turn of the millennium.

A part-time job becomes a full-time job

In 2000, Otte moved from Cambridge to Heidelberg where she found a job at Lion bioscience AG (later SYGNIS AG) and spent around three years on scientific projects and the development of a cellular test system for new drugs. In 2003, Otte became senior scientist in another Heidelberg-based company, Graffinity (later Santhera), where she was in charge of developing biochemical preclinical test systems and also of customer projects related to drug research. In addition to her job at Graffinity, the versatile molecular biologist accepted a position as lecturer in biotechnology at the Mannheim University of Applied Sciences.

Kerstin Otte soon realised that she loved working with students and eventually found the combination of this and research far more attractive than a purely academic position at a university. She therefore applied for positions at universities of applied sciences and ended up in Biberach, where she was one of the first professors to join Jürgen Hannemann, the founding dean of the Pharmaceutical Biotechnology course at Biberach University of Applied Sciences, in 2006.

Kerstin Otte would love to stay in Biberach as she sees the combination of scientific work and teaching as well as the region’s biopharmaceutical industry as being the ideal conditions for her work. Over the next five years, she will continue research into miRNA, concentrate on acquiring third-party funds and move into the new technology centre. It goes without saying that a research grant from the German Research Foundation (DFG) in the not-too-distant future would be another excellent achievement that she would be extremely pleased with.

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