Mateusz Sikora – Dioscuri Centre for Modelling of Posttranslational Modifications

Leader of the Dioscuri Centre: Dr. Mateusz Sikora
Partner from Germany: Prof. Dr. Gerhard Hummer, MPI of Biophysics
Host Institution: Małopolska Centre of Biotechnology, Jagiellonian University Krakow

Introduction

Proteins, which are made following the instructions from our DNA, get modified after they are created. These modifications are like adding special tags to the proteins that can change how stable they are, where they go in the cell, and how they interact with other molecules. When these modifications, known as post-translational modifications (PTMs), go wrong, they can lead to various diseases like brain disorders, skin problems, or cancer. Also, harmful organisms like viruses can use PTMs to hide from our body's defense system.

To fight these diseases and protect against these harmful organisms, it's important to understand these modifications in detail at a molecular level. However, studying PTMs is tough because they are not only small, but also very dynamic, making them hard to see with traditional methods used in biology.

In our research centre, we use large supercomputers to simulate proteins with PTMs. By this “computational microscope” we can see how they impact proteins, and ultimately, the health of our cells. In the long run, by answering these questions, our research will lead to better therapies against pathogens and development of new classes of PTM-aware drugs.

Who We Are

Dioscuri Centres are research groups in Central and Eastern Europe, initialized by the Max Planck Society and jointly funded by German and Polish governments. Supported by partners from Germany, Dioscuri Centres are established at research institutions that offer an environment for cutting-edge research. Centres are funded for an initial five years and can be extended for a further five years after successful evaluation by external experts.

Open Position

Staff Scientist. This is a hybrid IT-research position. We are looking for an IT expert to help maintain our local HPC and IT resources, but also to participate in the research of the group. See [here] for more details.

If you are interested in working with us (even if no openings are announced) please drop a line to Matt Sikora, we are constantly searching for motivated individuals!

About the PI

Mateusz Sikora, previously a Postdoctoral Fellow at the MPI for Biophysics (Frankfurt) also affiliated with the University of Vienna, first studied at the Jagiellonian University in Krakow (Poland) and then earned his PhD at the Institute of Physics of the Polish Academy of Sciences in Warsaw. In 2012, he went to Austria as a postdoc at the Institute of Science and Technology (IST Austria). Since 2017, Sikora had been working at the MPI for Biophysics in Gerhard Hummer's Department for Theoretical Biophysics within the framework of an Erwin Schrödinger Fellowship abroad funded by the Austrian Science Fund FWF. From May 2023, Sikora established the Dioscuri Centre for Modelling of Posttranslational Modifications at the Małopolska Centre of Biotechnology (at Jagiellonian University).

Key Collaborators

Gerhard Hummer (partner group), MPI of Biophysics, Frankfurt, Germany
Cyril Hanus lab, INSERM Paris, France
Danny Hsu lab, Academia Sinica, Taipei, Taiwan
Peter Hinterdorfer, Johannes Kepler University, Linz, Austria

Selected Group Publications

Tsai, Y. X.; Chang, N. E.; Reuter, K.; Chang, H. T.; Yang, T. J.; von Bülow, S.; Sehrawat, V.; Zerrouki, N.; Tuffery, M.; Gech, M.; Grothaus, I. L.; Colombi Ciacchi, L.; Wang, Y. S.; Hsu, M. F.; Khoo, K. H.; Hummer, G.; Hsu, S. T. D.; Hanus, C.; Sikora, M.

Rapid simulation of glycoprotein structures by grafting and steric exclusion of glycan conformer libraries.

BioRxiv

DOI

von Bülow, S.; Sikora, M.; Blanc, F. E. C.; Covino, R.; Hummer G.

Antibody accessibility determines location of spike surface mutations in SARS-CoV-2 variants.

PLOS Computational Biology 19 (1), e1010822 (2023)

Zhu, R.; Canena, D.; Sikora, M.; Klausberger, M.; Seferovic, H.; Mehdipour, A. R.; Hain, L.; Laurent, E.; Monteil, V.; Wirnsberger,G.; Wieneke, R.; Tampé, R.; Kienzl, N. F.; Mach, L.; Mirazimi, A.; Oh, Y. J.; Penninger, J. M.; Hummer, G.; Hinterdorfer, P.

Force-tuned avidity of spike variant-ACE2 interactions viewed on the single-molecule level.

Nature Communications 13 (1), 7926 (2022)

Slováková, J.; Sikora, M.: Nur Arslan, F.; Caballero-Mancebo, S.; Krens, S. F. G.; Kaufmann, W. A.; Merrin, J.; Heisenberg, C. P.

Tension-dependent stabilization of E-cadherin limits cell–cell contact expansion in zebrafish germ-layer progenitor cells.

Proceedings of the National Academy of Sciences 119 (8), e2122030119 (2022)

Sikora, M.; von Bülow, S.; Blanc, F. E. C.; Gecht, M.; Covino, R.; Hummer, G.

Computational epitope map of SARS-CoV-2 spike protein.

PLOS Computational Biology 17, e1008790 (2021)

Turoňová, B.; Sikora, M.; Schürmann, C.; Hagen, W. J. H.; Welsch, S.; Blanc, F. E. C.; von Bülow, S.; Gecht, M.; Bagola, K.; Hörner, C.; van Zandbergen, G.; Landry, J.; de Azevedo, N. T. D.; Mosalaganti, S.; Schwarz, A.; Covino, R.; Mühlebach, M. D.; Hummer, G.; Locker, J. K.; Beck, M.

In situ structural analysis of SARS-CoV-2 spike reveals flexibility mediated by three hinges.

Science 370, pp. 203 - 208 (2020).

Tsai, T.Y.-C.; Sikora, M.; Xia, P.; Colak-Champollion, T.; Knaut, H.; Heisenberg, C. P.; Megason, S. G.

An adhesion code ensures robust pattern formation during tissue morphogenesis.

Science 370 (6512), pp. 113 - 116 (2020)

Sikora, M.; Ermel, U. H.; Seybold, A.; Kunz, M.; Calloni, G.; Reitz, J.; Vabulas, R. M.; Hummer, G.; Frangakis, A. S.

Desmosome architecture derived from molecular dynamics simulations and cryo-electron tomography.

Proceedings of the National Academy of Sciences 117 (44), pp. 27132 - 27140 (2020)

Schmalhorst, P. S.; Deluweit, F.; Scherrers, R.; Heisenberg, C. P.; Sikora, M.

Overcoming the limitations of the MARTINI force field in simulations of polysaccharides.

Journal of Chemical Theory and Computation 13 (10), pp. 5039 - 5053 (2017)

Sikora, M.; Sułkowska, J. I.; Cieplak, M.

Mechanical strength of 17 134 model proteins and cysteine slipknots.

PLOS Computational Biology 5 (10), e1000547 (2009)

Other Web Profiles

Our website in Krakow: https://mcb.uj.edu.pl/en_GB/sikora-lab

Twitter: https://twitter.com/BioPhysMatt

Software

GlycoSHIELD is a tool and a Web application (glycoshield.eu) that allows users to rapidly graft glycan conformers onto protein structures. The tool has been created in collaboration with Cyril Hanus lab and Danny Hsu lab.