Migration of malignant B cells and their adaptive response to BCR inhibitor therapy

We are looking for a motivated PhD student that would like to work on the following project funded by the ERC (European Research Council) Starting grant. Chronic lymphocytic leukemia (CLL) is the most common adult leukemia and it seems that its pathogenesis is not directly driven by a mutation or genomic aberration. We and others have described that CLL cells are dependent on constant re-circulation between peripheral blood and lymph nodes where they obtain pro-survival and pro-proliferative signals. We have a novel model to study the subpopulation of CLL cells that have recently interacted in the lymph node microenvironment. Studying these cells allowed us to describe a novel mechanism of BCR regulation mediated by microenvironmental signals (Pavlasova et al…Mraz, Blood, 2016; Pavlasova et al….Mraz, Leukemia, 2018). Recently, the “BCR inhibitors” such as ibrutinib were approved for CLL therapy, and their mechanism of action largely depends on inhibition of CLL recirculation. However, molecular mechanisms regulating B cell re-circulation and mechanisms leading to resistance and adaptation to BCR signalling inhibitors are unknown (Pavlasova et al..Mraz, Blood, 2016; Cerna et al…Mraz, Leukemia, 2018).The samples collected during the administration of BCR inhibitors (e.g. Ibrutinib, Idelalisib) were already analyzed in the lab for gene expression. This let to the identification of a possibly novel regulator of CLL cells migration to and from lymph node compartment, which also contributes to CLL cells activation and survival. The student will further validate candidate molecules involved in CLL re-circulation, and adaptive mechanisms that leukemic cells utilize to survive therapy.
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 supervisor and submit a CV by email to: [Email Address Removed] (Subject: PhD School).
The PhD will start approx. Sept 2019
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.

To apply please contact the supervisor and submit a CV by email (Subject: PhD School) to: [Email Address Removed].
Information about the laboratory at ceitec.cz/mrazlab