Adaptive Immunity

Project Title: T-cell signaling in models of human diseases
Supervisor: Ondřej Štěpánek

Project Description
T cells represent the adaptive arm of immunity against infections and cancers. However, T cells also induce autoimmune diseases when they lose self-tolerance. The key to the biology of T-cells is their unique antigen receptor, which discriminates self and non-self antigens. Moreover, additional receptors and signaling pathways modulate T-cell fate decisions. The student will discover novel mechanisms in key T-cell signaling pathways and investigate their importance in established animal models of infection, cancer, and autoimmunity. The Lab of Adaptive Immunity offers a productive and stimulating environment (see our recent publications). We have established multiple national and international collaborations and we are well supported by domestic and international research grants. Our lab is the first and only immunological research group with an ERC grant in the country.

Candidate Profile
We are looking for highly motivated and smart candidates with a master degree in immunology, cell biology, molecular biology, biochemistry, medicine or a related field. The candidate must be able to communicate in English. Additional skills and experience (wet lab, coding, languages etc.) are appreciated but not essential. If you want to make a huge step towards your successful career in life sciences, get great theoretical and practical skills, and finish your PhD with a decent research paper in a timely manner, do not hesitate to apply! The student will receive 24,000 CZK salary plus a non-taxable stipend of 10,500 CZK per month. The candidates are strongly encouraged to contact the PI, Ondrej Stepanek, directly.

Suggested reading

1. Dynamics of the Coreceptor-LCK Interactions during T Cell Development Shape the Self-Reactivity of Peripheral CD4 and CD8 T Cells. Horkova V, Drobek A, Mueller D, Gubser C, Niederlova V, Wyss L, King CG, Zehn D, Stepanek O. Cell Rep. 2020 Feb 4;30(5):1504-1514.e7.
2. Strong homeostatic TCR signals induce formation of self-tolerant virtual memory CD8 T cells. Drobek A, Moudra A, Mueller D, Huranova M, Horkova V, Pribikova M, Ivanek R, Oberle S, Zehn D, McCoy KD, Draber P, Stepanek O. EMBO J. 2018 Jul 13;37(14):e98518. doi: 10.15252/embj.201798518.
3. Coreceptor scanning by the T cell receptor provides a mechanism for T cell tolerance. Stepanek O, Prabhakar AS, Osswald C, King CG, Bulek A, Naeher D, Beaufils-Hugot M, Abanto ML, Galati V, Hausmann B, Lang R, Cole DK, Huseby ES, Sewell AK, Chakraborty AK, Palmer E. Cell. 2014 Oct 9;159(2):333-45. doi: 10.1016/j.cell.2014.08.042.

Location
Prague, Czech Republic, Central Europe
The Lab of Adaptive Immunity at the Institute of Molecular Genetics of the Czech Academy of Sciences headed by Ondrej Stepanek focuses on the T-cell signaling, T-cell diversity, and T-cell fate decisions.

Molecular mechanisms of Bardet-Biedl Syndrome
Bardet-Biedl syndrome (BBS) is a rare hereditary disease belonging to a group of ciliopathies, i.e., syndromes caused by a dysfunction of primary cilia. Primary cilia are specialized cellular organelles that function as cellular antennae by perceiving extracellular stimuli and transducing them through a multitude of signalling cascades. In our laboratory, we study the primary cilia and the BBSome complex, which facilitates transport of various signaling receptors into and out of the cilium. The BBS1 subunit is mutated most frequently and currently 24 BBS-causative mutations in BBS1 were identified in human patients.
The aim of this project is the identification of the pathology of the individual human mutations on the molecular and cellular level. The student will characterize the pathogenic BBS1 variants in our established cell line models. The analysis will include fluorescence microscopy techniques and methods of molecular biology.

We are looking for an ethusiastic student of cell biology, molecular biology, biochemistry or a related field who is motivated to work on a project with biological and medicinal relevance. Bachelor students are also very welcome.

We offer

• The project is tailored for MSc. student with a high chance of a publication in an international journal.
• The student will master multiple modern techniques of cell biology, molecular biology and microscopy.
• We are a young research group with a strong publication record.
• Excellent infrastructures of the Institute of Molecular Genetics.
• Overall, this position is a perfect step towards your career in life-science.

How to proceed
If interested, please, contact the supervisor Dr. Martina Huranová (martina.huranova@img.cas.cz).

Further reading

1. Niederlova V, Modrak M, Tsyklauri O, Huranova M*, Stepanek O*: Meta-analysis of genotype-phenotype associations in Bardet-Biedl Syndrome uncovers differences among causative genes. Hum Mutat. 2019 Nov;40(11):2068-2087. 
2. Prasai A, Schmidt Cernohorska M, Ruppova K, Niederlova V, Andelova M, Draber P, Stepanek O*, Huranova M*:The BBSome assembly is spatially controlled by BBS1 and BBS4 in human cells. J Biol Chem. In press. 
3. Tsyklauri O, Niederlova V, Forsythe E, Drobek A, Prasai A, Sparks K, Trachtulec Z, Beales PL, Huranova M*, Stepanek O*: Altered hematopoietic system and self-tolerance in Bardet-Biedl Syndrome. BioRxiv, doi: 2020.02.24.962886