How do lipids, proteins, ions and water act together in biological membranes? How can we design medical drugs that specifically modulate membrane function? Questions like these are in the focus of our interdisciplinary biophysics team in the framework of our program “membrane medicine”. Research is motivated by pressing needs in human health care, regarding in particular the rapid increase in pathogenic bacteria that are multi-resistant to antibiotics or the treatment of cancer with poor prognosis.
To accomplish our goals we exploit the biophysical principles of (patho) physiological processes in biological membranes, viewing membranes on the one hand as meeting and interaction place of lipids, proteins and membrane active compounds, and on the other hand as complex, multifunctional interface for diverse cellular processes. Special attention is paid to the functional role of membrane lipid architecture. This approach is innovative and distinct from current high-throughput strategies in industrial research. Our vision is to derive novel compounds that will be finally used in medical treatment. First compounds are currently intensively tested for medical-technical applications.
To create an integrative approach from basic research to the design of membrane specific drugs we team up from three groups: the Lohner group works on peptides (= small proteins) to treat bacterial infections and related sepsis. The Zweytick group uses a similar approach. Here the goal is to kill specifically cancer cells. The Pabst group, finally, focusses on the physical principles of these applications.
Aim of our research is to elucidate the molecular mode of action of antimicrobial peptides to design novel antibiotic agents that combat bacteria which are multi-resistant to conventional antibiotics. Our knowledge is fundamentally based on understanding how these peptides discriminate between host and bacteria at which lipid composition of plasma membrane plays an essential role. Thus we have been studying the interaction of natural and synthetic antimicrobial peptides with membrane mimetic systems and cell membranes using thermodynamic, spectroscopic and structural techniques. Within the framework of an EU-project coordinated by myself a world-wide patent was granted to a family of peptides derived from lactoferrin, a protein highly concentrated in human colostrum (“first milk”).
Research is focused on physical principles that pertain to the function of biological membranes with the aim to aid the development of specific membrane active compounds (peptides). For example we are studying the role of physical properties of membrane domains (rafts) in protein (ion channels, receptors) sorting and functioning, effects of the aqueous environment (pH, ion specificity, etc.), or the elastic response of membranes to peptide insertion. The approach involves a broad selection of biophysical techniques, such as small angle x-ray (neutron) scattering, calorimetry, or fluorescence microscopy to name but a few.
We work on the development of new therapies for cancer, which are derived from human host defense peptides. They act independently of cancer type and can be even used to treat cancer with poor prognosis and treatability, such as glioblastoma or malignant melanoma. Their targets are lipids specifically exposed by cancer cells. The selective peptides are optimized in model- and in vitro systems, revealing mechanism as induction of apoptosis or necrosis. To illuminate the differences between neoplastic and non-neoplastic cells as well as peptide interaction with lipids of cancer membranes diverse methods are used such as fluorescence spectroscopy and -microscopy, calorimetry, small angle x-ray scattering and others. The results gained so far enabled us to submit an international patent application for a specific set of antitumor peptides.
Start: October 2020, IMB, Biophysics division, working group Zweytick