Our laboratory studies the structure and function of enzyme complexes in the mitochondrial respiratory chain by 3D electron microscopy. Our main emphasis is on the structure of complex I (NADH:ubiquinone oxidoreductase). Complex I is one of the entry points in the respiratory chain. It oxidizes NADH and in this process translocates protons across the inner mitochondrial membrane. Eukaryotic complex I has a molecular weight almost 1 MDa and is one of the largest membrane proteins in the mitochondrial inner membrane. It consists out of more than 40 individual subunits. 14 of the subunits are conserved throughout all species and are also found in bacterial complex I. We have shown, that not only are the central subunits conserved for all species but also its basic shape is the same for the yeast Yarrowia lipolytica, for bovine complex I and bacterial complex I (Aquifex aeolicus).
A second topic of our research is the development of new methods for 3D reconstruction of macromolecular assemblies and sub-cellular components. Methods include 3D reconstruction algorithms for conical tomography, the random conical reconstruction techniques combined with algorithms for 3D reconstruction from randomly oriented projections and techniques for reference based 3D reconstruction and refinements using Radon transform / polar Fourier transform based correlation methods. A fast reconstruction algorithm we developed is the two-step 3D Radon inversion algorithm. Currently we are developing 3D multivariate statistical techniques applicable to volumes with missing data, for the analysis of conformational variations in 3D data sets.