Přehled

Doctoral study program: Biomedical Sciences (Faculty of Medicine, Masaryk University)

Study plan: Molecular Medicine

Form of study: doctoral full time

Department: CEITEC MU and Dept of Internal Medicine, Hematology and Oncology

Supervisor: Mgr. Miroslav Boudny, Ph.D.

Consultant: Prof. Marek Mraz, MSc., MD, Ph.D.

Annotation

Non-coding RNAs (ncRNAs) represent the largest fraction of genes in human genome (up to 100 000) with microRNAs representing the best studied class (Nobel price for discovery in 2024). Aberrant expression of ncRNAs has been observed in almost every type of cancer. The first link between ncRNA dysfunction and cancer development came from studies of microRNAs in chronic lymphocytic leukemia (CLL) where miR-15/16 deletion is the most frequent genetic aberration and directly leads to leukaemia onset. Recently, it has been recognized that a characteristic feature of CLL is that cell survival and proliferation fully depend on signals from the microenvironment, especially T-cell interactions and B-cell receptor signaling (Hoferkova et al, Leukemia, 2024; summarized in Hoferkova et al., Cancers 2022). We have recently described for the first time that miRNAs are involved in the regulation of CLL interactions with T cells (Sharma et al., Blood 2021). However, it remains largely unknown what other ncRNAs regulate microenvironmental interactions in CLL. To study microRNAs and long non-coding RNAs involved in microenvironmental interactions, we performed their global profiling in “resting” vs “activated” CLL cells (NGS with Illumina, preliminary data available). We hypothesize that differently expressed ncRNAs are directly or indirectly involved in cell signaling induced by contact with the microenvironment and thus contribute to the regulation of CLL cell survival and proliferation. We have validated that knock-down or over-expression of several of the candidate ncRNAs affect microenvironmental interactions in CLL.

The project’s goal will be to study regulation through ncRNAs and the function of selected microRNA/lncRNA in the context of the CLL and lymphoma microenvironment. Experimentally, the project will include techniques such as NGS, immunoblotting, qPCR, transfections, cloning, viral transductions, genome editing (RNA interference and CRISPR), luciferase assay, RNA sequencing. We utilize cell lines as models and validate observations on primary CLL cells from patients and in mouse models.

Recommended literature

  • Kipps et al., Chronic Lymphocytic Leukaemia. Nature Reviews Disease Primers, 2017, https://doi.org/10.1038/nrdp.2016.96.
  • Sharma et al., Mir-29 Modulates CD40 Signaling in Chronic Lymphocytic Leukemia by Targeting TRAF4: An Axis Affected by BCR Inhibitors. Blood, 2021, https://doi.org/10.1182/blood.2020005627.
  • Hoferkova et al., In Vitro and in Vivo Models of CLL–T Cell Interactions: Implications for Drug Testing. Cancers, 2022. https://doi.org/10.3390/cancers14133087.
  • Zeni and Mraz, LncRNAs in adaptive immunity: role in physiological and pathological conditions. RNA Biology, 2020.

Research area: Cancer biology

Keywords: miRNA, CLL, T cell, microenvironment

Funding of the PhD candidate: Part-time salary (min. 0,5 FTE) on AZV/GACR grants + national scholarship (equals approx. half-time salary); guaranteed net income after taxes of min. 25.000 CZK

Requirements for candidate

  • Master’s degree in Molecular biology, Biochemistry, or similar field of study
  • Experience of working in a laboratory
  • The ability of collective work as well as independent project planning
  • Desire to learn new things

Information about the supervisor

Eleven years of experience in chronic lymphocytic leukemia research, first-author publications in Q1 journals (Boudny, Haematologica 2019; Boudny, Cancer Treatment Reviews 2020; total 63 citations), internship at the University of Birmingham in research group of Tatjana Stankovic, supervision of students (supervisor of 2 diploma and 4 bachelor students, co-supervisor of 1 diploma student). Extensive experience in the fields of cancer biology, hematology, immunology.

More at: https://is.muni.cz/auth/person/393305 and https://orcid.org/0000-0001-5757-0424.

Lab funded by prestigious grants (ERC, EHA, AZV, GAČR).

More information about the research group: http://mrazlab.ceitec.cz/

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

Application webpage: https://www.ceitec.eu/regulation-of-microenvironmental-interactions-in-chronic-lymphocytic-leukemia-by-non-coding-rnas/t11428

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