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Thesis title: Pharmacometrics of nuclear receptor-regulated gene expression dynamics

Annotation:
Pharmacometrics is a dynamically evolving interdisciplinary science that exploits mathematical and statistical modelling to describe, quantify and predict the effects of therapeutics on individual and groups (populations) of biological preparations, animals, or human subjects from data generated during pre-clinical (both in vitro and in vivo) and clinical studies. The analysis of such data requires an understanding of the underlying science and includes methods, such as pharmacokinetic/pharmacodynamic modelling, statistics, and parameter estimation methods. The role of pharmacometrics has become vital in decision making regarding drug development and translational research.

Our interdisciplinary research focuses on the development of novel, biologically based mathematical models of nuclear receptor activation and associated target gene regulation. Nuclear receptors are drug- or hormone-activated transcription factors which are essential for drug metabolism in the liver and intestine. We are looking for a Ph.D. student who will develop mathematical models to describe pharmacodynamic effects of drugs binding to nuclear receptors with respect to a variety of conditions, such as variable or repeated drug dosage. The results of the student’s work are expected to be published in high-level international journals.

The student will study at the Faculty of Pharmacy of Charles University in Hradec Králové in the Pharmacology and Toxicology doctoral program (https://www.faf.cuni.cz/Studium/Doktorske-studium/Farmakologie-a-toxikologie/) and will closely collaborate with the research group Clinical and molecular pharmacology (https://portal.faf.cuni.cz/Groups/Group-of-Clinical-and-Molecular-Pharmacotherapy/). Informal inquiries about the position are encouraged and welcome. Application deadline to the Ph.D. program is November 30th, 2021.

Funding: Funding will be provided by the faculty as a monthly stipend of 15,000 CZK. The student will also receive additional monthly stipend of approximately 11,670 CZK from the PRIMUS grant. The stipend will be further increased after completion of the state doctoral exam (+2,000 CZK) and after a three-month long research internship abroad (+500 CZK per completed internship) in accordance with the internal funding policy. The student will be welcome to apply for additional funding via the internal grant agency of Charles University GAUK (https://cuni.cz/UK-9291.html). Monetary bonuses will be granted for high-quality publications. Altogether, this Ph.D. stipend is highly competitive in the Czech Republic and enough to provide a comfortable student life in Hradec Králové.

Housing: The Ph.D. student can apply for accommodation at the dormitories. Alternatively, we will be happy to help with finding private housing.

Recommended literature:

  1. Duintjer Tebbens, Jurjen, Malek Azar, Elfriede Friedmann, Martin Lanzendörfer, and Petr Pávek. 2018. „Mathematical Models in the Description of Pregnane X Receptor (PXR)-Regulated Cytochrome P450 Enzyme Induction“. International Journal of Molecular Sciences 19, no. 6: 1785. https://doi.org/10.3390/ijms19061785
  2. Duintjer Tebbens, J., Matonoha, C., Matthios, A. et al. On parameter estimation in an in vitro compartmental model for drug-induced enzyme production in pharmacotherapy. Applications of Mathematics 64, 253–277 (2019). https://doi.org/10.21136/AM.2019.0284-18
  3. Smutny, T., Bernhauerova, V., Smutna, L. et al. Expression dynamics of pregnane X receptor-controlled genes in 3D primary human hepatocyte spheroids. Archives of Toxicology (2021). https://doi.org/10.1007/s00204-021-03177-y

Qualifications:

  • Masters degree or equivalent in mathematics, statistics, biostatistics, mathematical biology, pharmacometrics or related field
  • Good programming skills or willingness to learn (MATLAB, Python or related)
  • Good command of English (spoken and written)
  • Good communication skills and willingness to work in interdisciplinary and international environments

Net monthly stipend: 26,670 CZK

Application should include: A CV, a scanned copy of the Masters diploma or an official letter certifying its upcoming completion, brief motivation letter and contact information of two references should be sent via email to bernhauve@faf.cuni.cz before November 25th, 2021.
Informal inquiries to be sent to: Mgr. Veronika Bernhauerová, Ph.D. (bernhauve@faf.cuni.cz)