Is the Job related to staff position within a Research Infrastructure? No

Offer Description

Doctoral study program: Biomedical Sciences

Form of study: doctoral full time

Supervisor: Mgr. Miroslav Boudny, Ph.D.

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

Topic title: Regulation of microenvironmental interactions in chronic lymphocytic leukemia by non-coding RNAs

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. https://www.tandfonline.com/doi/full/10.1080/15476286.2020.1838783.

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 + doctoral scholarship + CEITEC PhD School scholarship. Guaranteed net income after taxes of min. 29.400 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

Start date: February 2027 or sooner

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

Where to apply

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

Work Location(s)

Number of offers available: 1

Company/Institute: CEITEC MU

Country: Czech Republic

City: Brno

Postal Code: 625 00

Street: Kamenice 753/5