Přehled

Doctoral study program: Life Sciences (Faculty of Science, Masaryk University)

Supervisor: doc. Mgr. Lukáš Trantírek, Ph.D.

Consultant: RNDr. Silvie Trantírková, Ph.D.

Annotation: 

In-cell NMR spectroscopy has emerged as a unique and powerful approach for probing biomolecular structure, dynamics, and interactions directly within living human cells under near-physiological conditions. It holds transformative potential for both basic biomedical research and pharmaceutical development, enabling direct analysis of drug-target engagement, binding affinities, and structural validation in the cellular context. However, current applications of in-cell NMR remain largely confined to asynchronous, 2D monocultures of immortalized or cancer-derived cell lines. This narrow experimental window limits both biological relevance and translational potential.

In our previous work, we successfully addressed key limitations of in-cell NMR by establishing two innovative strategies: (1) structural characterization in cell cycle–synchronized cells and (2) in-cell NMR within 3D human tissue spheroids. These efforts provided essential proof-of-principle for expanding the applicability of the technique to more complex biological systems.

Building on this foundation, the proposed project aims to take a critical step forward by developing and applying in-cell NMR spectroscopy in 3D human organ models derived from pluripotent stem cells. These models represent the current gold standard for replicating organ-level physiology in vitro, offering unprecedented opportunities to study molecular events within realistic tissue architecture and differentiation contexts. The PhD candidate will develop protocols for isotope labeling, sample handling, and NMR acquisition in stem cell-derived 3D tissues.

Recommended literature:

  • Theillet FX, Luchinat E. In-cell NMR: Why and how? Prog Nucl Magn Reson

Spectrosc. 2022 Oct-Dec;132-133:1-112.

  • Theillet FX. In-Cell Structural Biology by NMR: The Benefits of the Atomic

Scale. Chem Rev. 2022 May 25;122(10):9497-9570.

  • Luchinat E, Banci L. In-cell NMR: From target structure and dynamics to drug

screening. Curr Opin Struct Biol. 2022 Jun;74:102374.

  • Rynes J, Istvankova E, Dzurov Krafcikova M, Luchinat E, Barbieri L, Banci L,

Kamarytova K, Loja T, Fafilek B, Rico-Llanos G, Krejci P, Macurek L, Foldynova-

Trantirkova S, Trantirek L. Protein structure and interactions elucidated with

in-cell NMR for different cell cycle phases and in 3D human tissue models.

Commun Biol. 2025 Feb 7;8(1):194.

Research area: cellular and structural biology, NMR spectroscopy;

Keywords: in-cell NMR spectroscopy; protein; organoid; 3D cell culture; drug screening;

Funding of the PhD candidate: GACR LA grant (GF24-10605K) & IP (0151) (PI: Lukas Trantirek)

Requirements for candidate:

Master’s degree in Molecular or Cellular Biology/ Biochemistry /Chemistry / Biophysics

Prior experience with organoid production, induced pluripotent stem cells (iPSCs), or protein NMR spectroscopy is considered an asset.

Information about the supervisor

Supervisor: Prof. Lukas Trantirek (senior Research group leader Non-Coding Genome) supervised > nine PhD students at Masaryk University.

Research output summary

Research publications: 85
Reviews/books chapter: 4
Patent: 1 (US & EU), 1 pending patent application
Total citations: 2600+
H-index: 30
Publication highlights: Cell, J. Am. Chem. Soc., Angewandte Chemie, Nucleic Acids Res., PNAS, Nature Comm.
Reviewing activities: Nature Protocols, Nature Communications, Angewandte Chemie, Nucleic Acids Research, PNAS, Chemical Science, Chemical Reviews, J. Am. Chem. Soc., Chem. Sci…

Information about the application process: https://www.ceitec.eu/ls-mm-phd/

Application webpage:https://www.ceitec.eu/protein-in-cell-nmr-spectroscopy-in-3d-stem-cell-derived-human-organ-models/t11589

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