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Regulation of cell migration in B cell leukemias and lymphomas


Faculty of Medicine

About the Project

Supervisor: Josef Večeřa, Ph.D.

Co-supervisor: assoc. prof. Marek Mráz

PROJECT:

We are looking for a motivated PhD student for a project funded by ERC Grant (Marek Mraz lab, http://www.ceitec.cz/mrazlab). The project goal is to understand the molecular machinery that regulates the migration of malignant B cells between different niches such as lymphoid and bone marrow niche and peripheral blood. This is of great interest, especially in chronic lymphocytic leukemia (CLL). In CLL, but also in other lymphomas, the malignant B cells permanently re-circulate from peripheral blood to lymph nodes and back, and blocking this recirculation can be used therapeutically since malignant B cell depend on signals in immune microenvironment. However, the factors that regulate this are mostly unclear. The lab established several models for in vitro and in vivo studies of microenvironmental interactions and their interplay (unpublished in vivo model; Pavlasova et al. Blood, 2016; Pavlasova et al. Leukemia, 2018; Musilova et al. Blood, 2018; Mraz et al. Blood, 2014; Cerna et al. Leukemia, 2018).

We have identified candidate molecules that might act as novel regulators of the B cell migration or the balance between homing and survival in peripheral blood. This will be further investigated by the PhD student using technics such as genome editing (CRISPR), RNA sequencing, use of primary samples, functional studies with various in vitro and in vivo models. The research is also relevant for understanding resistance mechanisms to BCR inhibitors, pre-clinical development of novel drugs and their combinations (several patents submitted by the lab)

WHAT DO WE OFFER:

Modern laboratories, project funded by the prestigious ERC grant = high risk and high gain, state-of-the-art instrument, stable funding, competitive scholarship
You will work in a team of young investigators that challenge some long standing problems in the field of hematology. We do basic science, but with the objective to help patients in the future (we have access to primary samples with hem. malignancies, and we suggest novel clinical trials).
WHAT WILL YOU LEARN/DO:

How to think and work independently as a scientist
Writing of abstracts and papers (and course in grant writing and presentation of data)
How to present data and will attend conferences to present your research
You will spend 1-2 months visit(s) in collaborating labs in Europe or US
Collaboration with experts in wet lab research and bioinformatics
Novel methods such as Next Generation Sequencing (Illumina) and genome editing (Crispr).
How to critically analyze scientific data (regular journal clubs)
Classical methods of molecular biology (e.g. immunoblotting, flow cytometry, qRT-PCR, cell cultures, cloning), and you will use our in vitro models for microenvironmental interactions, and artificial activation/inhibition signalling pathways to decipher the gene regulatory loops.
You can supervise bachelor and diploma students if interested
WHO ARE WE LOOKING FOR:

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.

HOW TO APPLY:

To apply please contact the co-supervisor and submit a CV by email to:  and  (Subject: PhD School).
Information about the laboratory at: ceitec.cz/mrazlab; The PhD will start approx. Feb 2021

OTHER INFO:

The research is funded by ERC grant, and will be conducted at CEITEC MASARYK UNIVERSITY (campus Bohunice). Our laboratory extensively collaborates with the University Hospital Brno in the same campus to obtain primary samples from patients. The campus provides a vibrant, multidisciplinary and highly collaborative scientific environment. The lab is located in Brno, the second-largest city in Czech Republic that has the biggest concentration of biomedical research in the region. Brno is one of the major cultural hubs, with a vibrant and lively atmosphere housing ~60.000 students. The city has a very good public transport and plenty of interesting places to visit within the reach of trains (within small distance of several major cities such as Prague, Vienna, Bratislava, Budapest) and close to international airports.

Keywords: B-cell receptor signaling, BCR, leukemia, lymphoma, B cell malignancies, miRNAs, lncRNAs, mRNAs, NGS data analysis, genome editing, Crispr

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