Project: T-cell kinases in immunity and self-tolerance
Supervisor
Ondřej Štěpánek
Project description
The project will investigate the role of SRC-family kinases LCK and FYN in the T-cell antigen receptor signaling, which is crucial for proper T-cell development and immune response. It is known for decades that LCK, and to lesser extent FYN, catalyze the first biochemical step in TCR signaling, i.e., tyrosine phosphorylation of activation motifs in the TCR/CD3 complex. However, the role of these kinases in particular biological context is still incompletely understood. This project is a follow-up to our previous studies (Stepanek et al. 2014, Cell Horkova et al. 2020 Cell Reports, Horkova et al. 2023 Nature Immunology) and focuses mostly on the role LCK and FYN in the peripheral responses and in particular cells types. We have generated a genetically modified mouse model that enables cell specific and/or time-induced deletion of LCK. We will use this novel model together with other established models (whole-body LCK, FYN knock-outs, LCK knock-in mouse unable to bind to CD4 and CD8 co-receptors, TCR transgenic mice) to address:
The role of LCK and FYN in the differentiation of helper CD4 T cells into particular subtypes during infection.
The role of LCK and FYN in the function of regulatory T cells in autoimmunity and cancer.
Join a thriving, internationally recognized research group focusing on cutting-edge immunological studies.
Candidate profile
A Master’s degree (or expected graduation by October 2025) in biology, immunology, medicine, or a related field.
Exceptional problem-solving and critical thinking skills.
Strong motivation, dedication to scientific research, and eagerness to learn and master new techniques.
Proficiency in English (both written and verbal communication).
Integrity, responsibility, and a team-oriented mindset.
Suggested reading
Ondrej Stepanek, Arvind S Prabhakar, Celine Osswald, Carolyn G King, Anna Bulek, Dieter Naeher, Marina Beaufils-Hugot, Michael L Abanto, Virginie Galati, Barbara Hausmann, Rosemarie Lang, David K Cole, Eric S Huseby, Andrew K Sewell, Arup K Chakraborty, Ed Palmer: Coreceptor scanning by the T cell receptor provides a mechanism for T cell tolerance. Cell 2014 159(2): 333-45. [pubmed] [doi]
Horkova V, Drobek A, Paprckova D, Niederlova V, Prasai A, Uleri V, Glatzova D, Kraller M, Cesnekova M, Janusova S, Salyova E, Tsyklauri O, Kadlecek TA, Krizova K, Platzer R, Schober K, Busch DH, Weiss A, Huppa JB, Stepanek O: Unique roles of co-receptor-bound LCK in helper and cytotoxic T cells. Nat Immunol 2023 24(1): 174-185. [pubmed] [doi]
Horkova V, Drobek A, Mueller D, Gubser C, Niederlova V, Wyss L, King CG, Zehn D, Stepanek O: Dynamics of the Coreceptor-LCK Interactions during T Cell Development Shape the Self-Reactivity of Peripheral CD4 and CD8 T Cells. Cell Rep 202030(5): 1504-1514.e7. [pubmed] [doi]
