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Merckle Research Prize for excellent research

Three of the four scientists from the University of Ulm who have been awarded the 27th Merckle Research Prize are in the field of life sciences. The prizes, each with a purse of 5,000 euros, were awarded to Richard Schlenk, Bernd Baumann and Dirk Volkmer.

Richard Schlenk (Department of Internal Medicine III) received the award for his achievements in leukaemia research. Schlenk discovered that certain gene modifications or their combinations predict how well AML (acute myeloid leukaemia) patients respond to chemotherapy, the probability of AML recurrence and the chances of cure.

Molecular genetics technique allows better outcome prediction

Dr. Richard Schlenk (Photo: University Hospital Ulm)
AML is the most common type of acute leukaemia in adults. The outcome of the disease in those affected is usually assessed on the basis of the chromosomal alterations in leukaemia cells. Traditional diagnoses involve the analysis of the chromosome bands, which however, fails to reveal any mutations in 50 per cent of all AML patients. In such cases, leukaemia is classified as AML with normal karyotype.

For many years, the light microscope has been the principal tool for classifying the various forms of AML, but it has never been suitable for the detection of genomic alterations in cytogenetically normal AML patients or for the assessment of the clinical importance of such alterations. Molecular genetics techniques make this distinction possible. Scientists and doctors from the Department of Internal Medicine III at the Ulm University Hospital and colleagues from the Hanover Medical School also participated in the study.

Schlenk’s results have shown that AML patients with genomic alterations of unfavourable prognostic significance have a greater chance of cure following the transplantation of allogeneic bone marrow or haematopoietic stem cells. On the other hand, good-prognosis patients did not benefit from this intensive therapy and can be spared from unnecessary transplant-related morbidity. The genomic alterations identified by Schenk and his colleagues and their prognostic significance have been taken into account in the WHO’s current AML classification.

How do gene regulators work in diseased cells?

Dr. Bernd Baumann (Photo: University of Ulm)
Bernd Baumann from the Institute of Physiological Chemistry received the award for the development of transgenic mouse models. Such mice can be used to analyse the functions of specific gene regulators (NF-κB) in stroke and pancreatitis.

The NF-κB transcription factors, which are found in almost all body cells, control gene expression. Sustained NF-κB activity has emerged as the hallmark of a number of human diseases. Baumann succeeded in creating transgenic mouse strains in which these transcription factors could be selectively changed in disease-associated neurones and pancreatic acinar cells almost arbitrarily at any time.

This highly selective modulation is advantageous because the suppression of these gene expression regulators in all cells would lead to severe and even fatal consequences for the organism.
Transgenic mouse models with active and inactive system for the modulation of NF- B activity in brain neurones (left) and pancreatic acinar cells (right). (Photo: University of Ulm)
Transgenic mouse models with active and inactive system for the modulation of NF-κB activity in brain neurones (left) and pancreatic acinar cells (right). (Photo: University of Ulm)
The mouse model allows the researcher to find out how these transcription factors affect gene expression. This might enable the development of therapies that preclude the need to interfere with the physiological functions of NF-κB. The method enables researchers to use living animals to assess whether the NF-κB modulation machinery is active in a given organ. Baumann found out that the mouse neurones are more severely damaged, with fatal consequences, in cases where NF-κB is overactive. In contrast, damaged neurones survived far better when the NF-κB transcription factors were blocked. The scientists even found that the neurones recovered and were still alive several days after stroke.

Use of inhibitors is being assessed

According to Baumann, the influence of NF-κB on the development and course of acute pancreatitis is still unclear. Using mouse models, Baumann nevertheless succeeded in showing that experimental pancreatitis could be considerably attenuated by suppressing NF-κB gene activity in pancreatic acinar cells. The selective activation of NF-κB in acinar cells is detectable very early in the course of experimental pancreatitis.

Based on these findings, the researchers are assessing the therapeutic application of NF-κB gene inhibitors in stroke and acute pancreatitis. Baumann’s team is investigating the effect of the long-term modulation of NF-κB activity on the physiology of neurones and acinar cells.

Nature as role model: biomimetic materials

Prof. Dirk Volkmer (Photo: University of Ulm)
Dirk Volkmer, chemist at the Institute of Inorganic Chemistry II at Ulm University, received the Merckle Research Prize for the development of biomimetic materials. His team focused on the transfer of biological structures and syntheses to technical systems.

In the course of evolution, biological organisms have developed many materials that are interesting as models for novel construction materials, and also for medical applications. Biomimetic materials are generally characterised by multifunctional properties that always represent a (sensible) compromise. According to Volkmer, nature only uses a combination of a few, easily available constituents in a building-block system to make new materials. The specific modification of interfaces often plays a decisive role in this process.

Trying to unveil the secret of nacre

Biomineralisation is a clear example of such strategies. Mineralised hard tissues are common in the animal kingdom. Examples of such hard tissues include vertebrate bones and mollusc shells.

The iridescent interior of mussel shells is a difficult nut to crack: The nacre layer consists of a composite material composed of aragonite and a small but decisive proportion of specialised organic molecules.

Despite intensive research, the researchers have so far not succeeded in unveiling the secret of nacre biosynthesis. However, recent investigations, by researchers in Volkmer’s laboratory amongst others, have provided new insights into how this might be possible. Volker’s team used simple models to show that biomimetic strategies are used to produce nacre-like surfaces. The Ulm scientists are currently advancing these model studies in pilot projects to make biomimetic processing and process technologies available for technically relevant systems.

From coatings to new bone substitutes

Biomimetic materials can be used for a broad range of applications, e.g., corrosion-resistant coatings for offshore building constructions, to anti-scratch car varnish and medical applications like innovative bone replacement materials, for example.

The use of mussel shells as a model for innovative materials is only one example of biomimetic processes. Volkmer’s team is currently focusing on other projects, for example the development of structured surfaces based on the model of butterfly wings or the imitation of viruses using self-organising supramolecular containers that can be used to transport pharmaceutically active substances into cells.

Source: University of Ulm press release - 11 November 2008 (wp - 28 November 2008)
Website address: https://www.gesundheitsindustrie-bw.de/en/article/press-release/merckle-research-prize-for-excellent-research