PhD student profiles

     
     
   
Felix Schumacher

Micha Kunze
Micha joined the ISMB's Wellcome Trust 4-year Interdisciplinary PhD Programme in Autumn 2010.

Project title
Structure-Dynamics-Function Relationship of Metalloproteins: Coupling Magnetic Resonance Spectroscopy and Simulation

Principal investigator: Dr D. Flemming Hansen
Co-investigators: Dr Christopher W.M. Kay and Prof Peter V. Coveney

 

Background
From 2006 to 2009 I studied physics at the University of Osnabruck in Germany, where I graduated as B.Sc. with the thesis topic “EPR Spectroscopy on Spin Labelled Anthrax Lethal Factor “ in the group of Prof. Dr. H.-J. Steinhoff.

After I graduated I joined the group of Dr. Christopher W.M. Kay at the ISMB as a research fellow, where I was concerned with the application of electron paramagnetic resonance in nano and life- science. During my time in Germany and in the group of Dr. Christopher W.M. Kay I was the holder of scholarship from the German National Academic Foundation. In 2010 I got a studentship by the Wellcome Trust on the 4-year interdiscplinary PhD programme in structural, chemical and computational biology, where I am currently in my third year.

 

Current research
Our research is concerned with the detailed understanding of enzymatic function of metallo proteins, especially the human histone deacetylase 8. This hydrolase is a key entity in gene- regulation via the charge modulation of N-terminal histone lysine side chains and has been recently identified as drug target for the treatment of several cancers. For such an enzyme, the global stucture and dynamics are important, which are characterized by its architecture spanning several nanometers and motions in the microsecond and millisecond regime. However, in the active site, where HDAC8 comprises a divalent metal ion, sub angstrom geometric structural arrangements and dynamics on the femtosecond to nanosecond regime are important to yield an optimized electronic structure of the metal site.

To get a wholistic view on the enzymatic function of these proteins we have to bridge gaps of several orders of magnitude in space and time. We try to achieve this by employing a cross- discplinary approach where we apply advanced magnetic resonance techniques, molecular dynamics simulation as well as quantum chemistry calculations.

This research relies on strong interactions of the disciplines involved, which is possible at the ISMB as it provides the expertise and resources all in close vicinity, fostering interdiscplinary work between disciplines and departments.

 
figure


Publications

Micha Ben Achim Kunze , David W. Wright , Nicolas Daniel Werbeck , John Kirkpatrick , Peter Vivian Coveney , and D. Flemming Hansen. Loop Interactions and Dynamics Tune the Enzymatic Activity of the Human Histone Deacetylase 8. J. Am. Chem. Soc., Just Accepted Manuscript DOI: 10.1021/ja408184x Publication Date (Web): October 30, 2013.

Balian, S. J.; Kunze, M. B. A.; Mohammady, M. H.; Morley, G. W.; Witzel, W. M.; Kay, C. W. M.; Monteiro, T. S. Measuring central-spin interaction with a spin-bath by pulsed ENDOR: Towards suppression of spin diffusion decoherence. Physical Review B 2012, 1–6.

Hansen, D. F.; Westler, W. M.; Kunze, M. B. A.; Markley, J. L.; Weinhold, F.; Led, J. J. Accurate structure and dynamics of the metal-site of paramagnetic metalloproteins from NMR parameters using natural bond orbitals. Journal of the American Chemical Society 2012, 134, 4670–82.

Valentini, S.; Cabreiro, F.; Ackerman, D.; Alam, M. M.; Kunze, M. B. A.; Kay, C. W. M.; Gems, D. Manipulation of in vivo iron levels can alter resistance to oxidative stress without affecting ageing in the nematode C. elegans. Mechanisms of Ageing and Development 2012, 133, 282–90.

Phan, G.; Remaut, H.; Wang, T.; Allen, W. J.; Pirker, K. F.; Lebedev, A.; Henderson, N. S.; Geibel, S.; Volkan, E.; Yan, J.; Kunze, M. B. A.; Pinkner, J. S.; Ford, B.; Kay, C. W. M.; Li, H.; Hultgren, S. J.; Thanassi, D. G.; Waksman, G. Crystal structure of the FimD usher bound to its cognate FimC-FimH substrate. Nature 2011, 474, 49–53.

 

 

*




   
     
Institute of Structural and Molecular Biology, University of London
ismb-admin@ismb.lon.ac.uk
ucl logospacerbirkbeck logo