Molecular Interactions and Macromolecular Assemblies
Protein folding and assembly are processes governed by a large number of non-covalent protein-protein interactions as well as interactions between the proteins and their environment. Within this area of research we study the relative contribution of different types of non-covalent interactions to protein folding and oligomerisation. Furthermore, we study the functional consequences of protein-ligand interactions and the regulation of these interactions. An intriguing aspect of protein self-assembly is the formation of amyloid fibrils, underlying several human diseases. At the Department we study proteins from Alzheimer, Parkinson and Huntington’s diseases as well as diabetes and Frederich’s ataxia. By designing self-assembling polypeptides we test our knowledge of factors controlling protein folding and association.
Bioelectrochemical Studies of Direct and Mediated Electron Transfer between Redox Enzymes, Biological Membranes, Living Cells and Electrodes
It is natural to study electron transfer reactions with electrochemical techniques. However, when it comes to biological redox reactions, in most cases the distance between the site of the electron transfer and an electrode is too long to allow efficient electron transfer rates. Our studies are focused on understanding the processes of electron transfer between the electrodes and biological molecules, such as redox proteins, organelles, membranes, and whole cells. To optimise these processes we need, for example, to know how to arrange/orient the biomolecules on the electrode surface in a most efficient way. We also need to obtain thermodynamic and kinetic information on biological electron transfer reactions. The knowledge gathered in the basic science part of the project can be transfer to applications such as design of new biosensors and biofuel cells.
Principal investigator's involved in these projects: Lo Gorton.
Structural Biology of Enzymes and Large Macromolecular Assemblies
Within the area structural methods (X-ray crystallography, SAXS, cryo-EM) are used in the study of complex formation and dynamics of magnesium and cobalt chelatase, mechanism and allosteric regulation in ribonucleotide reductases and leukotriene converting enzymes, the role of metals in protein oligomerisation in various ataxias (neurodegenerative diseases) and structure-based design of new inhibitor compounds for enzymes from tropical parasites, particularly the malaria parasite. The group also plays an active role in running the protein crystallography beamlines at the MAX-lab synchrotron radiation facility, in planning the new beamlines at the MAX IV synchrotron, as well as in running the macromolecular crystallisation facility at Max-lab in collaboration with SARomics Biostructures AB. For educational material, please visit our educational site on protein structure and structural bioinformatics.
Membrane Protein Structure and Function
The area includes projects focused on the study of respiratory chain NADH:quinone oxidoreductase (Complex I), aquaporin membrane water channels and a technology platform for monitoring trans-membrane proton flux. This platform allows us to monitor proton translocation across a lipid bilayer quantitatively at ms time resolution and high sensitivity. The platform may be used for functional investigations of important membrane proteins, as well as investigating lipid bilayers of different composition.
RNA, DNA and Viruses
The work in the group focuses around studies of anticancer active drugs- and drug candidates and their interactions with DNA and RNA. We aim at identifying targets on DNA- or RNA-level that may facilitate the development of novel generations of highly efficient metal-based protocols for treatment of cancers. Current work in the group includes studies of platinum-, gold- and ruthenium-based anticancer active drugs and their influence on nucleic acid structure, transcription and protein translation. In a recently initiated project we are also investigating how short interfering RNAs (siRNA) might be used in combination with the metal-based drugs to optimize anticancer activity.
Principal investigator's in these groups: Sofi Elmroth; Alex Evilevitch.
Enzymology of hemicellulose hydrolysis
Hemicellulose polysaccharides, located in plant cell walls, are among the most abundant renewable resources on earth. We are studying the enzymatic hydrolysis of galacto(gluco)mannan, the major soft-wood hemicellulose polysaccharide. The aim is to understand the hydrolysis, which include several specific enzymes. We have been focusing on the structural and functional features of endo-mannanase, the major depolymerising enzyme, produced by the soil-fungus Trichoderma reesei. On the basis of the X-ray crystallographic 3D structure, an approach including site-directed and random mutagenesis is taken to determine functional important residues and regions.