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Biochemistry and Molecular Biology

Tutor Josef Lazar, Ph.D.

Josef Lazar

Topic Genetically encoded optical probes of activity of receptor kinases: development and applications in drug discovery

Receptor kinases (EGFR, FGFR, IGFR, insulin receptor and others) are membrane proteins crucial for many cell signaling processes. Using techniques of molecular biology, we will try to develop fluorescently labeled receptor kinase molecules that would allow observations of receptor kinase activation by two-photon polarization microscopy, an advanced optical microscopy technique developed by our laboratory. The ability to observe activity of the studied receptor kinases will be applied towards improvement in our understanding of receptor kinase function, as well as towards development of novel pharmaceutical drugs, such as antidiabetics.

Leading references:
Lazar J., Bondar A., Timr S., Firestein S.J.: Two-photon polarization microscopy reveals protein structure and function. Nature Methods 8: 684-690, 2011.
Bondar, A., and Lazar J.: The G protein Gi1 exhibits basal coupling but not preassembly with G protein-coupled receptors. Journal of Biological Chemistry 292: 9690-9698, 2017
Křížková K., Chrudinová M., Povalová A., Selicharová I., Collinsová M., Vaněk V., Brzozowski A.M., Jiráček J., Žáková L.: Insulin-Insulin-like Growth Factors Hybrids as Molecular Probes of Hormone:Receptor Binding Specificity. Biochemistry 55: 2903-2913, 2016.