Přehled

Doctoral study program: Life Sciences (Faculty of Science, Masaryk University)

Supervisor: Prof. Marek Mraz, MSc., M.D., Ph.D.

Consultant: Miroslav Boudny, Ph.D.

Annotation

Chronic lymphocytic leukemia (CLL) cells and indolent lymphomas are known to be dependent on diverse microenvironmental stimuli providing them signals for survival, development, proliferation, and therapy resistance. It is known that CLL cells undergo apoptosis after cultivation in vitro, and therefore it is necessary to use models of CLL microenvironment to culture CLL cells long-term and/or to study their proliferation. Several in vitro and in vivo models meet some of the characteristics of the natural microenvironment based on coculture of malignant cells with T-lymphocytes or stromal cell lines as supportive cell, but they also have specific limitations.

The aim of this research is to develop and use models mimicking lymphoid microenvironment to study novel therapeutic options, e.g. drugs targeting CLL proliferation, development of resistance in long-term culture or combinatory approaches, which cannot be analysed in experiments based on conventional culture of CLL/lymphoma primary cells. This project will utilize models developed in the laboratory and will further optimize and modify them. We have recently developed a co-culture model that is allowing to induce robust proliferation of primary CLL cells, something that was virtually impossible for decades (Hoferkova et al, Leukemia, 2024). Using kinase inhibitors, the biology of CLL and responses to targeted treatment will be interrogated. The student will utilize various functional assays, RNA sequencing, genome editing, drug screening etc., with the use of primary patient’s samples and cell lines. The research might bring new insights into the microenvironmental dependencies and development of resistance to targeted therapy.

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

Requirements for candidate

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

Application webpage: https://www.ceitec.eu/lymphoid-microenvironment-models-and-their-use-to-study-targeted-therapy-and-resistance-in-b-cell-malignancies/t11459