What are unique properties of cell membranes

Research: off through the cell membrane

The ÖAW Institute for Biophysics and Nanosystem Research was divided into three groups and linked to the TU, Med-Uni and Uni Graz. The research continues there.

The “super antibiotic” made the Institute for Biophysics and Nanosystem Research (IBN) famous last year: An active ingredient was developed here that perforates the cell wall of bacteria, i.e. kills bacteria quickly without them being able to develop resistance. This week was another milestone in the lives of the 30 or so researchers who work at the IBN on the outskirts of Graz: The institute, which has existed since 1968 (then specialized in X-ray research), will no longer be supported by the Austrian Academy of Sciences (ÖAW) from October , but is now divided between three universities in Graz (TU, Med-Uni and Uni Graz).

This happened as part of the reorganization of the Academy, which is based on a performance agreement with the Ministry of Science: The federal government will provide the Academy with a budget of around 224 million euros from 2012 to 2014. The resulting budget gap of 40 million euros will be filled by integrating individual OeAW institutes into universities. In this way, the employees keep their jobs, can continue all projects and continue to make the generated knowledge available to the world (see also article on the right).

Hammer effect.
The group around the former IBN director Karl Lohner, who caused a sensation with the super antibiotic, moves to the Karl-Franzens-Universität Graz (Institute for Molecular Biosciences). "Our research focuses on cell membranes: the shell that surrounds cells makes life possible because it separates the inside from the outside," reports Lohner. Many diseases have to do with processes on the cell membrane. This is exactly what drives the researchers: the hope of making disorders more recognizable and treatable. “We are looking for approaches that combat the major problem of antibiotic resistance and prevent the associated sepsis (colloquial: blood poisoning; note). Research is also being carried out on cancer and atherosclerosis, ”says Lohner.

Cell membranes are made up of two layers of fat molecules and regulate, among other things, the exchange of substances between the cell interior and blood, lymph, etc. "Changes in the physical properties of the cell membrane can influence its function," says Lohner. Georg Pabst in his team discovered, for example, that anesthetics that have been used successfully for 100 years (without knowing how they work in a molecular way) build themselves into the membranes at very specific points and thus inhibit the transmission of signals between nerve cells.

Lactoferrin, a protein from breast milk, served as a model for the development of the super antibiotic: “We have recreated an ancient defense mechanism.” The antibacterial effect of breast milk is due to the fact that lactoferrin makes small holes in the cell wall of bacteria. In the laboratory, the team synthesized small protein molecules that also “hammer holes” in bacterial walls. This is the big difference to conventional antibiotics: They attach to the bacteria with a "key" that has to fit into the "lock" of the bacterial receptors. However, bacteria can quickly change the lock through mutation. “The new antibiotic doesn't need a lock because it mechanically destroys the membrane,” enthuses Lohner.

His team is continuing the development of the new drugs in the spin-off company pba3. "Further research on similar active ingredients is now being carried out at the University of Graz," says Lohner. The great thing about how it works is that not only are bacteria destroyed, but toxins (endotoxins) of the bacteria are also bound. This prevents the deadly sepsis from which 200,000 people die every year in the United States. The new active ingredients also penetrate biofilms, which can lead to chronic inflammation on implants and which were previously difficult to access for antibiotics.

Dagmar Zweytick is now also doing research at the University of Graz: She is concentrating on the surface of cancer cells in order to identify which active substances can dock efficiently there. Precisely on the cancer cells and not on any other: This enables the development of new chemotherapeutic agents with fewer side effects. “The implementation of the approach for new therapies is to be tested in the mouse model. For the time being, we are concentrating on skin cancer, as the active ingredients can be administered superficially and thus reach their goal more easily, ”explains Lohner.

Targeted to the site of action. His IBN colleague Ruth Prassl took her team to the Medical University of Graz, where the ten employees will be part of the Institute for Biophysics from October. She is pleased that the newly formed research cooperation "BioTechMed" in Graz, which is supposed to make the Styrian life science sector even more visible internationally, will be strengthened by the connection. Prassl's team is dedicated to personalized medicine and develops “drug carriers”: that is, nanosystems that bring drugs to the target site in a more targeted manner and better adapted to the patient. This also increases the efficiency and reduces side effects. The current focus is on the early detection of atherosclerosis and the treatment of obesity and diabetes - the three diseases are mostly related.

When it comes to determining the structure of natural nanoparticles, Prassl's group is world class: Nobody knows the structure of the “bad” cholesterol carrier LDL in human blood as well as they do. This and similar natural nanoparticles serve as a model for synthetic carrier systems for drugs. For example, in cooperation with the Ludwig Boltzmann Institute for Pulmonary Vascular Research in Graz, we are looking for carriers that deliver active ingredients via inhaler directly into the lungs when they are inhaled.

("Die Presse", print edition, October 7, 2012)