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Supervisor:  Assoc. Prof. Marek Mraz, MSc., M.D., Ph.D.

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We are looking for a motivated PhD student that would like to work on the following project funded by the ERC (European Research Council) Starting grant  (Marek Mraz lab, www.ceitec.cz/mrazlab). Follicular lymphoma (FL) is a type of blood cancer that originates from B-lymphocytes, and it is the most common type of indolent non-Hodgkin lymphoma. The clinical course of FL patients can be surprisingly variable (survival from months to decades) and FL still remains incurable. The course of the disease is characterized by repeated relapses leading to the evolution of resistant disease or to the high-grade transformation to a more aggressive diffuse large B-cell lymphoma (DLBCL). This is associated with remarkably poor prognosis and a high risk of early death. Number of studies showed that multiple genetic lesions are associated with FL transformation (tFL); however, precise molecular mechanisms underlying this process is largely unclear. Importantly, the role of long non-coding RNAs in this process is completely unknown. However, we have recently described the role of short-noncoding miRNAs roles in transformed FL (Musilova et al…Mraz, Blood, 2018). The aim of the project is to reveal the molecular mechanisms involving lncRNAs and/or miRNAs responsible for FL transformation. The primary samples collected before and after high-grade transformation will be analyzed on the level of protein-coding as well as non-coding genes (NGS with Illumina, preliminary data available). This will be followed by searching for function of tFL-associated lncRNAs. This will help to better understand the disease biology and possibly to identify novel molecular targets that could be used therapeutically.

Recommended literature:

  • Sharma et al. …Mraz. miR-29 Modulates CD40 Signaling in Chronic Lymphocytic Leukemia by Targeting TRAF4: an Axis Affected by BCR inhibitors. Blood 2020 Nov (epub). https://pubmed.ncbi.nlm.nih.gov/33171493/
  • Musilova et al. …Mraz. miR-150 downregulation contributes to the high-grade transformation of follicular lymphoma by upregulating FOXP1 levels . Blood. 2018 Nov 29;132(22):2389-2400. https://pubmed.ncbi.nlm.nih.gov/33786575/
  • Musilova K, Mraz M. MicroRNAs in B-cell lymphomas: how a complex biology gets more complex. Leukemia. 2015 May;29(5):1004-17
  • Zeni and Mraz LncRNAs in adaptive immunity: role in physiological and pathological conditions.  RNA Biol. 2021 May;18(5):619-632. https://pubmed.ncbi.nlm.nih.gov/33094664/

Applications should include: a CV, a scanned copy of the Masters or an official letter certifying its completion, brief motivation letter, and contacts for at least two references should be sent via email marek.mraz@ceitec.muni.cz or phd@ceitec.muni.cz.

More information about CEITEC PhD School are available at http://ls-phd.ceitec.cz/.