Single Molecule Biophysics Laboratory
Chaperone mechanics
I was very fortunate to receive an offer of a Rosalind Franklin Fellowship to start my own research group at the University of Groningen in the Netherlands in the spring of 2020. Embedded within the Groningen Biomolecular Sciences and Biotechnology Institute (GBB), I am pursuing an independent research line in single-molecule biophysics. My major research goal is to further expand the capabilities of the optical tweezers for the study of protein structure, function and dynamics.
See also: https://www.rug.nl/research/gbb/research/pi/tych/
Publications
Aha1 regulates Hsp90’s conformation and function in a stoichiometry-dependent way, Tanumoy Mondol, Laura-Marie Silbermann, Julia Schimpf, Leonie Vollmar, Bianca Hermann, Katarzyna M Tych, Thorsten Hugel, Biophysical Journal 122(7), 2023
Book Chapter: Using Single-Molecule Optical Tweezers to Study the Conformational Cycle of the Hsp90 Molecular Chaperone, Katarzyna Tych and Matthias Rief, Optical Tweezers: Methods and Protocols pp. 401-425, Springer US, 2022
Controlling amyloid fibril properties via ionic liquids: The representative case of ethylammonium nitrate and tetramethylguanidinium acetate on the amyloidogenesis of lysozyme, Visakh VS Pillai, Pallavi Kumari, Srikanth Kolagatla, Victoria Garcia Sakai, Svemir Rudić, Brian J Rodriguez, Marina Rubini, Katarzyna M Tych, Antonio Benedetto, The Journal of Physical Chemistry Letters 13(30), 2022
Unbiased Data Analysis for the Parameterization of Fast Translocation Events through Nanopores, Florian LR Lucas, Kherim Willems, Matthijs J Tadema, Katarzyna M Tych, Giovanni Maglia, Carsten Wloka, ACS Omega 7(30), 2022
Perspective: A stirring role for metabolism in cells, Jose Losa, Simon Leupold, Diego Alonso-Martinez, Petteri Vainikka, Sebastian Thallmair, Katarzyna Tych, Siewert-Jan Marrink, Matthias Heinemann, Molecular Systems Biology 18 (4), 2022
Bioconjugation Strategies for Connecting Proteins to DNA-Linkers for Single-Molecule Force-Based Experiments, Lyan van der Sleen and Katarzyna Tych, Nanomaterials 11 (9), 2424, 2021
Mechanism of action of ionic liquids on the amyloidogenesis of lysozyme. Visakh Pillai, Katarzyna Tych, Marina Rubini, Brian Rodriguez, Antonio Benedetto, European Biophysics Journal with Biophysics Letters 50, p. 149, 2021
Observing the Regulation of the Hsp90 Chaperone by Co-Chaperones and Nucleotides. Katarzyna Tych, Markus Jahn, Hannah Girstmair, Thorsten Hugel, Johannes Buchner, Matthias Rief, Biophysical Journal 120 (3), 8a, 2021
Details of the Conformational Cycle of Hsp90 Probed using Optical Tweezers. Katarzyna Tych, Markus Jahn, Hannah Girstmair, Thorsten Hugel, Johannes Buchner, Matthias Rief, Biophysical Journal 118 (3), 198a, 2020
With personal funding through a prestigious Human Frontier Cross-Disciplinary Fellowship, KT used a custom-built optical tweezers setup combined with kinetic and mechanical biophysical models to study the details of the conformational cycle of the heat shock protein 90 (Hsp90) chaperone system.
Hsp90 is a molecular chaperone, meaning that it assists in the correct folding of other proteins. It is a dimeric ATP-driven molecular machine, and is one of the most abundant proteins found in eukaryotic cells. This specialised chaperone is known to function as part of several complexes to assist in several essential cellular functions, although the exact mechanisms by which these functions occur is not yet known.
Working in the lab of Prof. Matthias Rief, in collaboration with the lab of Prof. Johannes Buchner, KT worked towards delineating the specific domain orientations and forces that are required for the function of Hsp90. This will help us to understand how the conformations and mechanics of Hsp90 are influenced by co-chaperones and client proteins.
Publications
* indicates equal author contributions
The Hsp90 isoforms from S. cerevisiae differ in structure, function and client range
Hannah Girstmair, Franziska Tippel, Abraham Lopez, Katarzyna Tych, Frank Stein, Per Haberkant, Philipp Wener Norbert Schmid, Dominic Helm, Matthias Rief, Michael Sattler, Johannes Buchner
Nature Communications, 2019 doi: 10.1038/s41467-019-11518-w
Nucleotide-Dependent Dimer Association and Dissociation of the Chaperone Hsp90
Katarzyna Tych, Markus Jahn, Florian Gegenfurtner, Vera Hechtl, Johannes Buchner, Thorsten Hugel, and Matthias Rief
Journal of Physical Chemistry B, 2018 doi: 10.1021/acs.jpcb.8b07301
Stable sub-structures in proteins and how to find them using single-molecule force spectroscopy
Katarzyna Tych and Gabriel Zoldak
Protein Supersecondary structures (2nd Ed.), Methods in Molecular Biology, In Press, Springer, 2018
Folding and Domain Interactions of three orthologues of Hsp90 studied by single molecule force spectroscopy
Markus Jahn* and Katarzyna Tych*, Hannah Girstmair, Maximilian Steinmaßl, Thorsten Hugel, Johannes Buchner and Matthias Rief
Structure 26(1), 95 — 105, 2018
Extremophilic proteins
Extremophilic organisms are adapted to live and thrive under the most extreme conditions on Earth. For example, hyperthermophilic extremophiles have optimal growth temperatures of over 80°C. However, the protein-level adaptations that enable this remarkable thermal stability are not fully understood.
To study these fascinating proteins, KT designed and constructed an AFM with high precision temperature control and the capability to perform a variety of force application protocols. KT also developed a method to optimise calculation of energy landscape parameters from single molecule unfolding experiments.
Publications
* indicates equal author contributions
Differential effects of hydrophobic core packing residues for thermodynamic and mechanical stability of a hyperthermophilic protein
KM Tych, M Batchelor, T Hoffmann, MC Wilson, ML Hughes, E Paci, DJ Brockwell and L Dougan
Langmuir 32 (29), 7392-7402, 2016
Tuning protein mechanics through an ionic cluster graft from an extremophilic protein
KM Tych, M Batchelor, T Hoffmann, MC Wilson, E Paci, DJ Brockwell and L Dougan
Soft matter 12 (10), 2688-2699, 2016
Rapid and robust polyprotein production facilitates single-molecule mechanical characterization of β-barrel assembly machinery polypeptide transport associated domains
T Hoffmann* and KM Tych*, T Crosskey, B Schiffrin, DJ Brockwell, L Dougan
ACS nano 9 (9), 8811-8821, 2015
Life in extreme environments: single molecule force spectroscopy as a tool to explore proteins from extremophilic organisms
KM Tych, T Hoffmann, M Batchelor, ML Hughes, KE Kendrick, DL Walsh, M Wilson, DJ Brockwell and L Dougan
Biochemical Society Transactions 43 (2), 179 — 185, 2015
Optimizing the calculation of energy landscape parameters from single-molecule protein unfolding experiments
KM Tych, ML Hughes, J Bourke, Y Taniguchi, M Kawakami, DJ Brockwell and L Dougan
Physical Review E 91 (1), 012710, 2015
Single molecule force spectroscopy reveals the temperature-dependent robustness and malleability of a hyperthermophilic protein
KM Tych, T. Hoffmann, DJ Brockwell and L Dougan
Soft Matter 9 (37), 9016 — 9025, 2013
A single-molecule approach to explore the role of the solvent environment in protein folding
KM Tych and L Dougan
Proteins in Solution and at Interfaces: Methods and Applications in Biotechnology and Materials Science, John Wiley and Sons, 315 — 334, 2013
Towards design principles for determining the mechanical stability of proteins
T Hoffmann* and KM Tych*, ML Hughes, DJ Brockwell, L Dougan
Physical Chemistry Chemical Physics 15 (38), 15767 — 15780, 2013
Single-molecule force spectroscopy identifies a small cold shock protein as being mechanically robust
T Hoffmann* and KM Tych*, DJ Brockwell and L Dougan
The Journal of Physical Chemistry B 117 (6), 1819 — 1826, 2013
A small cold shock protein as a model for force spectroscopy studies of extremophilic proteins
T Hoffmann, KM Tych, DJ Brockwell and L Dougan
The FEBS Journal 279, 514, 2012
Terahertz time-domain spectroscopy
My PhD research focused on terahertz time-domain spectroscopy (THz-TDS). The THz region of the electromagnetic spectrum, usually defined to span from 0.1 - 10 THz, is sensitive to intramolecular motions
associated with the internal chemical structure of molecules and from intermolecular motions on time scales of 0.1 - 10 ps. Clear differences between THz spectra of crystalline and amorphous samples can be observed, because of the long-range lattice vibrations in crystalline samples.
In biological molecules, THz-TDS can distinguish between DNA hybridisation states, between different proteins and even mutants of the same protein, and most interestingly THz-TDS can detect changes in absorption coefficient of a sample when a large-scale conformational change occurs.
I successfully modified existing THz-TDS equipment to allow the first reported measurements of protein crystals and developed a transfer-function-based method for the analysis of THz spectra.
Publications
Oxygen activation switch in the copper amine oxidase of Escherichia coli
TG Gaule, MA Smith, KM Tych, P Pirrat, CH Trinh, AR Pearson, PF Knowles and MJ McPherson
Biochemistry 57 (36), 5301 — 5314, 2018
Probing temperature-and solvent-dependent protein dynamics using terahertz time-domain spectroscopy
KM Tych, CD Wood, AD Burnett, AR Pearson, AG Davies, EH Linfield, JE Cunningham
Journal of Applied Crystallography 47 (1), 146 — 153, 2014
A simple transfer-function-based approach for estimating material parameters from terahertz time-domain data
KM Tych, CD Wood, W Tych
IEEE Photonics 6 (1), 1 — 11, 2014
Measurement and analysis of the diffuse reflectance of powdered samples at terahertz frequencies using a quantum cascade laser
P Dean, AD Burnett, K Tych, SP Khanna, M Lachab, JE Cunningham, EH Linfield, AG Davies
The Journal of chemical physics 134 (13), 134304, 2011
Applying broadband terahertz time-domain spectroscopy to the analysis of crystalline proteins: a dehydration study
KM Tych, AD Burnett, CD Wood, JE Cunningham, AR Pearson, AG Davies and EH Linfield
Journal of Applied Crystallography 44 (1), 129 — 133, 2011
Terahertz pulsed spectroscopic imaging using optimized binary masks
YC Shen, L Gan, M Stringer, A Burnett, K Tych, H Shen, JE Cunningham, EPJ Parrott, JA Zeitler, LF Gladden, EH Linfield and AG Davies
Applied Physics Letters 95 (23), 231112, 2009
Terahertz vibrational absorption spectroscopy using microstrip-line waveguides
MB Byrne, J Cunningham, K Tych, AD Burnett, MR Stringer, CD Wood, L Dazhang, M Lachab, EH Linfield and AG Davies
Applied Physics Letters 93 (18), 182904, 2008