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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 for a project funded by ERC Grant (Marek Mraz lab, www.ceitec.cz/mrazlab). The project goal is to understand the role of noncoding RNAs in the regulation of microenvironmental interactions in B cell malignancies. It has been shown that most of human genome is transcribed into RNA, but only a small percentage encodes proteins, while the rest has a variety of regulatory functions. The lab is deciphering novel mechanisms of BCR signaling regulation mediated by microenvironmental signals, such as BCR signaling and T cell interactions. We showed for the first time that non-coding RNAs, namely microRNAs (miRNAs), regulate the BCR signaling which opened an interesting field of research (Musilova et al. Blood, 2018; Mraz et al. Blood, 2014; Cerna et al. Leukemia, 2019; Sharma et al, EHA congress, 2020). Now we would like to reveal the role of lncRNAs in BCR signaling and other microenvironmental interactions of B cell leukemias and lymphomas. We aim to describe for the first time the functional relation of lncRNA with BCR signalling.

We have identified candidate long-noncoding RNAs (lncRNAs) that might act as novel regulators of the crosstalk of BCR signaling/T-cell interactions/adhesion in B cell malignancies. This will be further investigated by the PhD student using technics such as genome editing (CRISPRi), RNA sequencing, functional studies with various in vitro (primary cells and cell lines), and in vivo models. The research is also relevant for pre-clinical development of novel RNA-based therapeutics, and resistance mechanisms to BCR inhibitors.

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/

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/.