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Hatzakis Group

Our groups 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.

Research

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.

Facilities

The Nano-Enzyme Group labs are equipped with everything needed to perform state of the art experiments on a variaty of protein, enzyme and related experiments. Most experiments in the group are build around fluorescent microscopy, performed on one (or both) of two microscopes:

An IX81 Olympus confocal microscope
An Olympus Total Internal Reflection Fluorescence microscope (TIRFm) set up for super resolution microscopy

Additionally, the state of the art Olympus SpinSR10 (Spinning Disk Confocal Super Resolution Microscope) will be installed in the lab primo 2019, thus allowing us to extend our research to live cells.

Projects

The primary focus of our lab is to provide the molecular level mechanisms that underlie and control protein behavior with emphasis on structure function correlations and biomolecular interactions. The ultimate target is to utilize the attained knowledge for improving human health and for the design of tailor made biocatalysts for biotechnological, green energy, solutions. To succeed in this, and often inspired by nature, we develop biophysical assays in native-like membrane environments and employ biophysical tools that allow molecular interrogations with the unprecedented sensitivity of single-molecule readouts.

Focusing on a spectrum of biological systems, we investigate how the personality of a nanometer-dimension enzyme propagates to biological phenomena. As such, interrogating the structural and functional dynamics of an enzyme allows us to provide links between nanometer motions and ultrafast structural dynamics to human diseases, clinical phenotypes and industrial performance (e.g. detergents in industry). In a way, we strive to provide links of protein landscapes to clinical and industrial phenotypes.

All our projects are in tight collaboration with industrial partners (e.g. Novozymes), medical doctors, and biological labs and are at the interface between chemistry, biology, medicine and clinical biochemistry.

In 2015, Nikos S Hatzakis was awarded the prestigious Villum Young Investigator funding, that is directed to especially talented up-and-coming researchers in science and technology with ambitions of creating their own, independent research identity. With this grant, we equipped our lab with state-ofthe-art super-resolution single-molecule microscopes along with hiring new members.

Nanoenzymes 1

Publications

Selected publications

Funding

2014: Villum Foundation, Young Investigator Fellowship

2016: Novozymes A/S & The Henning Holck-Larsen Foundation, Guest Post-doctoral Fellowship

2016: Novo Scholarship Programme

2017: Carlsberg Foundation, Most Distinguished Associate Professor Fellowship

2017: Marie Curie, Post Doc Fellowship

2017: Lundbeck fonden, Post Doc Fellowship

2017: Velux foundation Center: Advanced Biomolecular Engineering

2018: Innovation Foundation Denmark, Industrial Post-doc

People

Associate Professor, group leader

Nikos S Hatzakis

Nanoenzymes Group
Nano Science Center
Department of Chemistry
Faculty of Science
hatzakis@nano.ku.dk

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.