The research in the Membrane Biochemistry & Biophysics group is focused on biological membranes. These membranes form the barriers that separate the inside from the outside of living cells and that define organelles within cells. They are essential for life.
Our main aim is to understand how membranes are built up and how they function at a molecular level. We investigate this by using a variety of systems, ranging from simplified self-assembled model membranes of lipids and proteins to membranes of living cells, and by using different complementary approaches, including molecular biology, chemical synthesis, analytical chemistry and advanced biophysical methods. Membrane proteins are vital for almost all cellular functions.
In more applied lines of research we investigate how membranes and membrane proteins are involved in the method of action of drugs, antibiotics and amyloid forming proteins and how this knowledge can be applied to combat diseases such as cancer, diabetes or resistance to antibiotics.
The main aim of the research of prof. dr. Antoinette Killian is to understand how membrane proteins are modulated by lipids in the membrane. This is accomplished on one hand by using a bottom-up approach involving simple, artificial model systems of designed transmembrane peptides in synthetic lipid bilayers. In a new and complementary line of research, the group explores the use of amphipathic polymers of styrene and maleic acid, which have the ability to solubilize membrane proteins directly from their native membrane in the form of nanodiscs. This allows the proteins to be captured, purified and studied together with their native lipids.
A more applied research line concerns the interaction of membranes with amyloid forming proteins, which have been associated with a wide range of diseases. The focus here lies on the mode of action of inhibitors of amyloid formation and how their effect is modulated by membranes.
Dr. Eefjan Breukink studies the bacterial cell wall synthesis pathway, which is the most accessible essential pathway of bacteria and hence a very important target for antibiotic development. Still little is known how the bacterial cell wall synthesis is regulated and part of his research is to to elucidate mechanism of regulation of the cell wall synthesis. The bacterial cell wall also provides a interesting target for antibiotics. With the ever-increasing prevalence of antibiotic resistance and the almost empty antibiotic pipelines of the pharmaceutical industry, there is a great need for the development of new antibiotics. In designing such new antibiotics, it is generally viewed optimal to look at the antibiotics that bacteria themselves use in their fight for survival. Evolutionary forces have shaped and continue to shape these antibiotics into excellent weapons. By learning how they work, new targets can be identified and we might be able to design better versions or even completely new antibiotics and so keep ahead in the arms race against resistant bacteria.
Dr. Toon de Kroon focusses on membrane lipid homeostasis. Membrane lipid composition determines the physical properties of biological membranes that are crucial for maintaining the membrane barrier and for the functioning of membrane proteins. Research in the group is aimed at understanding the principles that govern bulk membrane lipid composition and at identifying the underlying sensor-effector modules. These topics are investigated in the model eukaryote S. cerevisiae using biochemical, molecular biological, genetic and chemical biological approaches.