Offer Description
Doctoral study program: Life Sciences
Supervisor: Prof. Marek Mraz, MSc., M.D., Ph.D.
Topic title
Long Non-Coding RNAs as Novel Regulators of B-Cell Receptor Signaling and Microenvironmental Interactions in Chronic Lymphocytic Leukemia
Annotation
The development and progression of B-cell malignancies are critically influenced by signals originating from the tumor microenvironment. Over the past decade, non-coding RNAs have emerged as key regulators of cellular communication and signaling pathways in cancer. While microRNAs have been extensively studied and are known to play important roles in B-cell biology, the functions of long non-coding RNAs (lncRNAs) remain largely unexplored. Understanding how lncRNAs regulate malignant B-cell behavior represents one of the major unanswered questions in contemporary cancer biology.
This PhD project aims to uncover the role of lncRNAs in controlling B-cell receptor (BCR) signaling and B–T cell interactions, two fundamental processes that drive the pathogenesis of chronic lymphocytic leukemia (CLL). The project builds on the long-standing expertise of the research group in non-coding RNA biology and tumor–microenvironment interactions, supported by an ERC Starting Grant and multiple high-impact publications in the field. Preliminary data have identified several previously uncharacterized lncRNAs that are likely involved in regulating communication between CLL cells and their microenvironment.
The PhD candidate will investigate the molecular functions of these lncRNAs using a combination of state-of-the-art genetic, cellular, and biochemical approaches. A unique aspect of the project is the availability of newly generated lncRNA knockout mouse models, including mice carrying the genetic deletion of a candidate lncRNA. The student will characterize these models and combine them with established CLL mouse systems, including the Eu-TCL1 model, to determine the role of lncRNAs in leukemia development and progression in vivo. The project will further employ CRISPR interference technologies, RNA pulldown assays, transcriptomic analyses, and studies of primary patient-derived samples to identify molecular pathways and interaction partners controlled by candidate lncRNAs. In parallel, the student will take advantage of a recently developed co-culture system that enables robust proliferation of primary CLL cells in vitro, overcoming a major limitation in CLL research. This innovative platform will be used to perform the first CRISPR-based functional screens aimed at identifying lncRNAs and protein-coding genes that regulate the proliferation and survival of primary CLL cells. By integrating functional genomics, mouse modeling, and patient-based research, this project seeks to establish a comprehensive understanding of how lncRNAs shape B-cell signaling and microenvironmental responses in CLL. The findings are expected to reveal fundamental mechanisms of leukemia biology, identify novel therapeutic vulnerabilities, and generate insights that are broadly relevant to other B-cell malignancies, autoimmune diseases, and normal immune regulation.
This interdisciplinary project offers extensive training in molecular biology, cancer genomics, genome engineering, mouse models, and translational research, providing an excellent foundation for a scientific career in cancer and immunology research.
Recommended literature
- 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
- Mattick JS, et al. Long non-coding RNAs: definitions, functions, challenges and recommendations. Nat Rev Mol Cell Biol. 2023 Jun https://pubmed.ncbi.nlm.nih.gov/36596869/
- Sharma et al. …Mraz. miR-29 Modulates CD40 Signaling in Chronic Lymphocytic Leukemia by Targeting TRAF4: an Axis Affected by BCR inhibitors. Blood 2021. https://pubmed.ncbi.nlm.nih.gov/33171493/
- Musilova K, Mraz M. MicroRNAs in B-cell lymphomas: how a complex biology gets more complex. Leukemia. 2015 May;29(5):1004-17
Research area
Cancer biology
Keywords
lymphoma, CLL, lncRNA, microenvironment
Funding for the PhD candidate
In the academic year 2026/27 the net income of the CEITEC PhD School student is expected to be at least CZK 29,400 (approx. EUR 1215)
Part-time salary (min. 0,5 FTE) on EHA grant/AZV/GACR grants + doctoral scholarship + CEITEC PhD School scholarship.
Requirements on candidates
- Motivated smart people that have the “drive” to work independently, but also willing to learn from other people in the lab and collaborate.
- Candidates should have a master’s degree in Molecular biology, Biochemistry, or similar field and have deep interest in molecular biology and cancer cell biology.
Information about the supervisor
H-index 30 (citations > 3500, 50 publications with IF), currently principal investigator of 4 grants (AZV 3x, NPO, in the past ERC Starting grant). Dr. Mraz has currently 5 PhD students, with 2finishing soon). international collaborations: University of Southampton, Univ.California- San Diego, Mayo Clinic, Dana-Farber Cancer Institute, EMBL, University of Turin (student internship available), member of EHA Comittee, reviewer in scientific journals: Blood, Leukemia, Leukemia Research; https://is.muni.cz/auth/osoba/101627;
More information about the research group: http://mrazlab.ceitec.cz/
Start date: February 2027 or sooner
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