Nikos Hatzakis' main research interest is to obtain a fundamental understanding of the parameters underlying regulation of enzymatic function. Enzymes regulate a plethora of vital cellular processes and aberration in their function can result in countless disease states. They are also essential components in multiple industrial applications including drug synthesis and detergent development. Harnessing the biomolecular insights of current single molecule experiments allows us to unmask the structural and functional dynamics of major drug metabolism enzymes. Understanding how these enzymes operate paves the way for the design of novel pharmaceutics.
In spite of their immense importance, current understanding on enzymatic behaviour relies primarily on static pictures and ensemble functional assays and thus dynamic characteristics remain masked due to ensemble averaging. We therefore employ single molecule techniques to interrogate the behaviour of individual enzymes and elicit a detailed understanding of the molecular level details underlying enzymatic function and regulation. Using state of the art fluorescent microscopy techniques, we investigate how the complex protein conformational dynamics facilitate catalysis, as well as the existence and life times of enzymatic functional states and how point mutations, posttranslational modifications or effectors, redistribute them.
Advancing our understanding of functional protein dynamics will lead both to the design of novel pharmaceutics and the in silico design of novel biocatalysts with tailor made functionalities for biotechnological applications.
|2014-present||Associate Professor, Department of Chemistry, NanoScience Center|
|2011- present||Assistant Professor, Department of Neuroscience and Pharmacology and NanoScience Center.|
|2006-2011||Post doc, University of Copenhagen, NanoScience Center.|
|2004-2006||Post doc, Department of molecular and materials, University of Nijmegen, The Netherlands|
|1999-2003||PhD, University of Crete, Greece|
|1993-1997||BSc in Chemistry and Biochemistry, University of Crete, Greece|
Selected Scientific Publications
Laursen, T., Singha, A., Rantzau, N., Tutkus, M., Borch, J., Hedegard, P., Stamou, D., Møller, B.L., and Hatzakis, N.S. Single Molecule Activity Measurements of Cytochrome P450 Oxidoreductase Reveal the Existence of Two Discrete Functional States. Acs Chem. Biology 9, 630-634, doi:10.1021/cb400708v (2014).
Hatzakis, N. S. Single molecule insights on conformational selection and induced fit mechanism. Biophysical Chemistry 186, 46-54, doi:10.1016/j.bpc.2013.11.003 (2014).
Christensen, S. M., Bolinger, P.-Y., Hatzakis, N. S., Mortensen, M. W. & Stamou, D. Mixing subattolitre volumes in a quantitative and highly parallel manner with soft matter nanofluidics. Nature Nanotechnology 7, 51-55, doi:10.1038/nnano.2011.185 (2012).
Elizondo, E., Larsen, J., Hatzakis, N.S., Cabrera, I., Bjornhorn, T., Veciana, J., Stamou, D., and Ventosa, N. Influence of the Preparation Route on the Supramolecular Organization of Lipids in a Vesicular System. Journal of the American Chemical Society 134, 1918-1921, doi:10.1021/ja2086678 (2012).
Hatzakis, N. S., Wei, L., Jørgensen, S.K., Kunding, A.H., Bolinger, P.-Y., Ehrlich, N., Makarov, I., Skjot, M., Svendsen, A., Hedegard, P., Stamou,D. Single Enzyme Studies Reveal the Existence of Discrete Functional States for Monomeric Enzymes and How They Are "Selected" upon Allosteric Regulation. Journal of the American Chemical Society 134, 9296-9302, doi:10.1021/ja3011429 (2012).
Larsen, J., Hatzakis, N. S. & Stamou, D. Observation of Inhomogeneity in the Lipid Composition of Individual Nanoscale Liposomes. Journal of the American Chemical Society 133, 10685-10687, doi:10.1021/ja203984j (2011).
Bhatia, V. K., Hatzakis, N. S. & Stamou, D. A unifying mechanism accounts for sensing of membrane curvature by BAR domains, amphipathic helices and membrane-anchored proteins. Seminars in Cell & Developmental Biology 21, 381-390, doi:10.1016/j.semcdb.2009.12.004 (2010).
Hatzakis, N. S., Bhatia, V.K., Larsen, J., Madsen, K.L., Bolinger, P.-Y., Kunding, A.H., Castillo, J., Gether, U., Hedegard, P., and Stamou, D. How curved membranes recruit amphipathic helices and protein anchoring motifs. Nature Chemical Biology 5, 835-841, doi:10.1038/nchembio.213 (2009).