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Structure and Function of Biological Membranes
The laboratory is dedicated to advancing to a better understanding of the structure, function, and role of biological membranes in cells and cellular organelles. We put a special emphasis on the study of the structure and function of membrane molecules (lipids and proteins) and on the investigation of the mechanism by which these molecules control membrane permeability and cellular functions. We provide a multidisciplinary training and research environment including cell biology, physiology, biochemistry, proteomics, cell and molecular spectroscopy, biophysics and structural bioinformatics. As membrane component s are the targets for most pharmaceutical compounds, our studies include hot topics such as cancer diagnostic and treatment, cholesterol and lipid transport, Alzheimer's disease, cell transfection, heavy metals detoxification. Our group has contributed to the development of methodologies that allow the investigation of the structure-activity relationship of membrane proteins at a molecular scale in a well-defined environment. One of our main purpose is to stimulate and coordinate high-level graduate education in membrane biology, and foster career development of membrane scientists in an environment of research excellence. The laboratory develops Basic and Applied Research projects. Our laboratory belongs to the ''Structural Biology and Bioinformatics Center'' at the University of Brussels, and is member of the ''Structure and Function of Biological Macromolecules, Bioinformatics and Modelling'' graduate college. Our laboratory is also part of several European (Early Stage Training (EST)'' networks.
Exchangeable apolipoproteins play a critical role in plasma lipoprotein metabolism, first as structural components of lipoproteins, but also as activators of lipid metabolic enzymes at the surface of the lipoproteins and as ligands for cell surface receptors. These functions are extremely important in the transport and the metabolism of lipids and cholesterol into the blood stream. While the high-resolution structure of some of these proteins is known in the lipid-free state, much less is known about their lipid-bound conformations. Yet, these lipid-bound conformations are the most important ones because an essential step in the activation of these exchangeable apolipoproteins is their association with lipoprotein particles. Apolipoprotein E (apoE) is one of the most important exchangeable apolipoproteins. In the lipid-bound state, apoE is a ligand for most of the receptors of the low-density lipoprotein (LDL) receptor family. This makes apoE an extremely important anti-atherogenic component of the lipoprotein metabolism. We study apoE lipid-bound conformation(s) and its interaction with its receptor, using different biochemical and structural approaches (infrared spectroscopy, circular dichroism, NMR, and also bioinformatics). ApoE plays an extremely important role also in the central nervous system and seems to be involved in neuronal plasticity, repair and development. One isoform of apoE, apoE4 has been identified as one of the major risk factor in the development of Alzheimer's disease. ApoE is known to interact with the amyloid beta peptide, considered as one of the major culprits in Alzheimer's disease. One of our goals is to study, using different functional and structural approaches, the interaction of apoE with amyloid beta and to understand how apoE isoforms differentially modulates the amyloid beta conformation.