Biosketch

A truly multi-disciplinary scientist, Katarzyna (Kasia) Tych started her academic career as an electronic engineer, completing her PhD in 2011. During her PhD, she developed methods to enable the use of terahertz time-domain spectroscopy for measurements of high frequency vibrational modes in proteins. During her postdoctoral work with Prof. Lorna Dougan and Dr. David Brockwell (University of Leeds), she developed her passion for single-molecule protein biophysics through her studies of proteins from extremophilic organisms using atomic force microscopy (AFM). She went on to receive a prestigious cross-disciplinary fellowship from the Human Frontier Science Program to study the heat shock protein 90 (Hsp90) chaperone system using optical tweezers in the laboratory of Prof. Matthias Rief (Technical University of Munich, Germany). In 2020 she obtained a Rosalind Franklin Fellowship and tenure-track assistant professorship in single-molecule biochemistry at GBB (University of Groningen). Her research involves single-molecule characterisation of proteins using mass photometry (iSCAT), force spectroscopy and fluorescence with the optical tweezers and optical microscopy. In combination with structural work and biochemical studies, her group uses single molecule techniques to gain an in-depth understanding of structure-function-dynamics relationships in biological macromolecules. Her main current research interests include:

• Chaperone biophysics – answering fundamental questions about the function of the Hsp90 chaperone, among others;

• Transmembrane transporters – developing new methods by which we can access the dynamics and therefore understand the functions of these challenging, yet essential molecular machines;

• Single-molecule enzymology – watching enzymes in action and learning about how their functions are regulated.

Three top publications 2017-2022

1. Tych KM*, Jahn M*, Girstmair H, Steinmassl M, Hugel T, Buchner J & Rief M (2018) Folding and domain interactions of three orthologues of Hsp90 studied by single-molecule force spectroscopy. Structure 26(1): 96-105; DOI: https://doi.org/10.1016/j.str.2017.11.023

In this publication we were able to show clear differences in the inter-domain interactions and mechanical stabilities of three different orthologues of Hsp90, observing a surprisingly stable linker between the N-terminal domain and the middle domain of the endoplasmic reticulum Hsp90 (Grp94). We suggest that this plays a role in the mechanical coupling of the structure for Grp94 which, unlike Hsp82, does not have cochaperones which are known to regulate its large-scale conformational changes.

2. Tych KM, Jahn M, Gegenfurtner F, Hechtl VK, Buchner J, Hugel T & Rief M (2018) Nucleotide-dependent dimer association and dissociation of the chaperone Hsp90. The Journal of Physical Chemistry B 112(49): 11373-11380; DOI: https://doi.org/10.1021/acs.jpcb.8b07301

We demonstrated that nucleotide binding in the N-terminal domain of Hsp82 has a stabilising effect on the dimerization interface in the C-terminal domain.

3. van der Sleen LM & Tych KM (2021) Bioconjugation strategies for connecting proteins to DNA-linkers for single-molecule force-based experiments. Nanomaterials 11(9): 2424; DOI: https://doi.org/10.3390/nano11092424

We describe various methods for preparing proteins to be studied using the optical tweezers.