Mechanisms of the tolerance and homeostasis of immune cells

• Název práce v češtině: Mechanismy tolerance a homeostáze imunitních buněk
• Název v anglickém jazyce: Mechanisms of the tolerance and homeostasis of immune cells
• Klíčová slova: Bardet-Biedl syndrom, T lymfocyty, adaptivní imunita, signalizace
• Klíčová slova anglicky: Bardet-Biedl Syndrom, T cells, adaptive immunity, signaling
• Akademický rok vypsání: 2017/2018
• Typ práce: disertační práce
• Jazyk práce: angličtina
• Ústav: Katedra buněčné biologie (31-151)
• Vedoucí / školitel: Mgr. Ondřej Štěpánek, Ph.D.
• Řešitel: skrytý - zadáno vedoucím/školitelem
• Datum přihlášení: 17.10.2017
• Datum zadání: 17.10.2017
• Datum odevzdání elektronické podoby: 18.02.2022
• Datum proběhlé obhajoby: 29.04.2022
• Oponenti: prof. RNDr. Jan Černý, Ph.D.

Předběžná náplň práce v anglickém jazyce

BBSome is an octameric protein complex that facilitates trafficing of specific cargo proteins between cytosol and primary cilium. Mutations in BBSome subunits cause a severe multiorgan disease called Bardet-Biedl Syndrome (BBS). Because T cells do not form primary cilium, the role of the BBSome has not been addressed, yet. However, the immunological synapse, a contact site between a T cell and an antigen presenting-cell, exhibits some features of a primary cilium. For instance, proteins involved in ciliary trafficing, Rab8 and IFT20, are crucial for the polarization of T-cell antigen receptors towards the immunological synapse. Moreover, it has been shown that BBSome is required for targeting leptin receptor to the plasma membrane. Because leptin is an important modulator of T-cell biology, BBSome might play an important role in this regulatory pathway.
In this project, the applicant will analyze the immune system of a mouse model of BBS (BBS4 knock-out). She will focus on the development and function of lymphocytes using in vivo and in vitro models. In addition to the response to antigens, she will analyze selected signaling pathways (leptin, hedgehog, notch). To elucidate whether the observed phenotype is T-cell intrinsic, she will analyze also T-cell specific BBS4 knock-out driven by CD4-Cre. The applicant will take advantage of the models, techniques, and facilities available at the Group of Adaptive Immunity and at the Institute of Molecular Genetics (including transgenic mouse lines, Listeria monocytogenes infection, flow cytometry unit, microscopy, biochemical assays).