piwik-script

Intern
Rudolf-Virchow-Zentrum für Experimentelle Biomedizin

Über die AG Thorn

The determination of macromolecular structures forms the basis of today's molecular biology and biochemistry. However, these structures cannot be obtained from experimental data alone - a model is needed to interprete the measured images, and hence, understanding of the underlying principles is crucial. This understanding is the driving force behind our work, as it will allow us to improve all known structures and solve more challenging ones in the future. We achieve this objective by wet-lab experiments, theoretical big data analyses and by writing our own algorithms.

Crystallography: Better models and better data

In crystallography, the gap between model and reality is clearly evident in hard to interpret maps and large R values. This gap hinders in particular the determination of challenging structures, such as membrane proteins, where often only low resolution data are available. In these cases, the poor models currently obtainable result in noisy electron density maps that are difficult or even impossible to interpret. Shortcomings in the measurement and processing of X-ray data compounds the problem. Here, the lack of suitable diagnostics is a major roadblock. The resulting structures may not only be flawed or fail to answer the biological question, but downstream applications such as structure-based drug design or moelcular dynamics calculations also suffer. We aim to find out what is missing from these structural models, and in parallel, seek to improve crystallographic data quality with our diagnostic software AUSPEX (www.auspex.de) so that more structures can be elucidated, and existing ones can be improved. For this, we are collaborating with researchers ar the synchrotrons DLS (Oxfordshire, UK), BESSY (Berlin), ESRF (Grenoble, France), the ESS (Lund, Sweden) and the EuXFEL (Hamburg).

New modelling methods for Cryo-EM

In cryo electron microscopy, high resolution data became available only very recently (resulting in the 2017 Nobel Prize). As Cryo-EM maps have higher information content than X-ray data, they should, in principle, be superior to electron density maps of comparable resolution. However, Cryo-EM maps are currently modelled using methods originally developed for crystallography, even if the underlying assumptions are not always justified. This limits the answers we can obtain from these new high resolution data. We develop tools directly based on the nature of the cryo-EM experiment, such as the neural network Haruspex, in order to overcome these challenges.

Dr. Thorn's group is embedded in the Schindelin research lab.

Mostosi, P., Schindelin, H., Kollmannsberger, P., Thorn*, A. (2019) Automated interpretation of Cryo-EM density maps with convolutional neural networks.www.biorxiv.org/content/10.1101/644476v1 DOI: 10.1101/644476 [preprint]


Thorn, A., Parkhurst, J.M., Emsley, P., Nicholls, R., Evans, G., Vollmar, M., Murshudov, G.N. (2017) AUSPEX: a graphical tool for X-ray diffraction data analysis, Acta Cryst D73 729-737.


Parkhurst, J.M., Thorn, A., Vollmar, M., Winter, G., Waterman, D.G., Fuentes-Montero, L., Gildea, R.J., Murshudov G.N., Evans, G. (2017) Background modelling of diffraction data in the presence of ice-rings, IUCrJ 4, 626-638.


Thorn, A. (2017) Experimental Phasing: Substructure Solution and Density Modification as Implemented in SHELX, in Protein Crystallography, Methods in Molecular Biology (series), 357-376 co-editors A. Wlodawer, Z. Dauter, and M. Jaskolski, Springer. [invited book chapter]


Knott, G.J, Panjikar, S., Thorn, A., Fox, A.H., Conte, M.R., Lee, M., Bond, C.S. (2016) A crystallographic study of human NONO (p54nrb): Overcoming pathological problems with purification, data collection and non-crystallographic symmetry, Acta Cryst. D72, 761-769


Deigan Warner, K.D., Chen, M.C., Song, W., Strack R.L., Thorn, A., Jaffrey S.R., Ferré-D’Amaré, A.R. (2014) Structural basis for activity of highly efficient RNA mimics of green fluorescent protein , Nature Structural & Molecular Biology 21, 658–663


Thorn, A., Sheldrick G.M. (2013) Extending Molecular Replacement Solutions with SHELXE , Acta Cryst. D. 69, 2251-2256


Cooper, R.I., Thorn, A., Watkin D.J. (2012) CRYSTALS enhancements: asymmetric restraints, J. Appl. Cryst. 45, 1057-1060


Thorn, A., Steinfeld, R., Ziegenbein, M., Grapp, M., Hsiao, H.H., Urlaub, H., Sheldrick, G.M., Gärtner, J., Krätzner, R. (2012) Structure and activity of the only human RNase T2, Nucleic Acids Res. 40, 8733-8742


Thorn, A., Dittrich, B., Sheldrick, G.M. (2012) Enhanced rigid-bond restraints, Acta Cryst. A68, 448-451


Thorn, A., Sheldrick, G.M. (2011) ANODE: ANOmalous and heavy-atom DEnsity calculation, J. Appl. Cryst. 44, 1285-1287


Tavcar, G., Sen, S.S., Azhakar, R., Thorn, A., Roesky, H.W. (2010) Facile syntheses of silylene nickel carbonyl complexes from Lewis base stabilized chlorosilylenes Inorg Chem. 49, 10199-10202


Vouffo, B., Dongo, E., Facey, P., Thorn, A., Sheldrick, G. M., Maier, A., Fiebig, H.H., Laatsch, H. (2010) Antiarol cinnamate and Africanoside, a cinnamoyl triterpene and a hydroperoxy-cardenolide from the stem bark of Antiaris africana, Planta Med. 76, 1717-1723


Fischer, A., Stern, D., Thorn, A., Abraham, S., Stalke, D., Klingebiel, U. (2010) From the Lithium-2-anilide-2-fluoro-1,3-diaza-2-sila-cyclopentene-GaCl3 Adduct to 1,4,6-Triaza-5-gallium-7-sila-cyclo-3-heptene - Experimental and Quantum-chemical Results Z. Anorg. Allg. Chem. 636 (2010), 1527-1532


Vollmar, D., Thorn, A., Schuberth, I., Grond, S. (2009) A comprehensive view on 4-methyl-2-quinazolinamine, a new microbial alkaloid from Streptomyces of TCM plant origin, J. Antibiot. 62, 439-444


Thorn, A., Egerer-Sieber, C., Jäger, C.M., Herl, V., Müller-Uri, F., Kreis, W., Muller Y.A. (2008) The crystal structure of 5β-Progesterone Reductase from Digitalis Lanata defines of a novel subfamily of short-chain dehydrogenases/reductases, J. Biol. Chem. 283, 17260-17269


Tampier, S., Müller, R., Thorn, A., Hübner, E., Burzlaff, N. (2008) Synthesis, Structure and Reactivity of Ruthenium Carboxylato and 2-Oxocarboxylato Complexes bearing the Bis(3,5-dimethylpyrazol-1-yl)acetato Ligand, Inorg Chem. 47 , 9624-9641

 

Philipp Mostosi

Doktorand/in
Rudolf-Virchow-Zentrum für Experimentelle Biomedizin
Universität Würzburg
Josef-Schneider-Str. 2
97080Würzburg
Deutschland
Gebäude: Haus D15
Raum: 00.042

Dr. Andrea Thorn

Rudolf-Virchow-Zentrum für Experimentelle Biomedizin
Universität Würzburg
Josef-Schneider-Str. 2
97080Würzburg
Deutschland
Gebäude: Haus D15
Raum: 00.042

Current position

Junior group leader in the lab of Prof. Hermann Schindelin at the Rudolf Virchow Center of  University of Würzburg (since 2019)

Research Experience

2017-2019

Postdoctoral researcher in the research group of Prof. Hermann Schindelin, University of Würzburg, Germany

2016-2017

Postdoctoral researcher, University of Hamburg, Germany

2016

Senior Research Scientist, Diamond Lightsource, Oxford, UK

2013-2016

Investigator Scientist, MRC Laboratory of Molecular Biology, Cambridge, UK

2013

Post-doctoral research associate, University of Cambridge, UK

2011-2012

Postdoctoral researcher, Georg-August University Goettingen, Germany

Education

2008-2011

Dr. rer. nat, Georg-August University Goettingen, Germany (supervisor: Prof. George M. Sheldrick)

Fellowships, Awards and External Funding

  • BMBF „Erforschung der Materie an Großgeräten“ (2019)
  • DFG Sachbeihilfe (2019)
  • Rising Star Award, Asian Crystallographic Association (2013)
  • Marie-Curie IEF Fellowship (2013)

Selected activities

  • Vice president Computing Interest Group of the European Crystallographic Association (since 2018)
  • Member  of the IUCr Computing Commission (since 2017)
  • Scientific program director for the European Crystallographic Computing Forum 2018, Spain
  • Scientific program director for the European Computing School in Germany 2016 and in Croatia 2015
  • Council Member of the British Crystallographic Association (2013-2016)
  • Secretary Computing Interest Group of the European Crystallographic Association (2013-2018)

Member -Graduate School of Life Sciences

Dr. Thorn is lecturing on a number of international courses each year:

  • SeaCoast workshop (South East Asia) (January)
  • RapiData at Stanford Synchrotron Radiation Lightsource, US (April)
  • Cold Spring Harbor Course "Diffraction Methods", US (October)
  • Diamond-CCP4 Data Collection and Structure Solution Workshop in Oxfordshire, UK (December)
  • International CCP4 courses (varying dates and places)