"Mobilitas järeldoktori uurimistoetus" projekt MJD164
MJD164 "Mis reguleerib autoimmuunset reguleerijat? (1.06.2011−31.05.2014)", Mithu Guha, Tartu Ülikool, Tartu Ülikool, Arstiteaduskond.
Mis reguleerib autoimmuunset reguleerijat?
What Regulates the Autoimmune Regulator?
Teadus- ja arendusprojekt
Mobilitas järeldoktori uurimistoetus
ValdkondAlamvaldkondCERCS erialaFrascati Manual’i erialaProtsent
3. Terviseuuringud3.1. BiomeditsiinB500 Immunoloogia, seroloogia, transplantoloogia3.1. Biomeditsiin (anatoomia, tsütoloogia, füsioloogia, geneetika, farmaatsia, farmakoloogia, kliiniline keemia, kliiniline mikrobioloogia, patoloogia)100,0
Tartu Ülikoolkoordinaator01.06.2011−31.05.2014
Tartu Ülikool, Arstiteaduskondkoordinaator01.06.2011−31.05.2014
01.06.2014−31.05.201494 080,00 EUR
94 080,00 EUR

Escape of self-reactive T-cells in the body constitutes potential threat for autoimmunity. By eliminating these self-reactive T-cells, thymus plays a pivotal role in the development of central tolerance. Recognition of self-reactive cells depends on the expression of self-antigens’ repertoire in thymus. Autoimmune Regulator (AIRE1) is a nuclear protein involved in regulating the ectopic expression of self-antigens in thymus. Mutations in AIRE gene cause autoimmune disease, Autoimmune polyendocrinopathy Candidiasis Ectodermal Dystrophy (APECED). There are many studies on how AIRE regulates TRAs expression but so far there are few reports on how AIRE expression itself is regulated. Many studies implicate several members of the NF-kappaB signaling pathway on expression of aire gene. But there is lack of information on AIRE gene enhancer region. Enhancer region of genes determine cell-type-specific gene expression on a global scale and are functionally active in a cell-type-specific manner. Based on the existing knowledge, that enhancers are the main transcriptional regulatory element guiding gene expression in cell-type-specific manner as well as existence of putative binding sites for thymus specific transcription factor in AIRE gene motivate us to investigate enhancer region of AIRE gene. Investigation will begin with identification of enhancer region of AIRE gene which will be followed by experimental validation of identified enhancer region of AIRE gene using suitable reporter gene assay e.g. luciferase or flourescent protein expression. Validation will be followed by a systemic study for identification of transcription factor binding to enhancer region of AIRE gene. Finally, identified enhancer region will be tested in in vivo conditions using animals having either deletion or mutation in enhancer region. Completion of the study would provide vital clues on regulatory element of AIRE gene and its regulatory mechanisms which indirectly affects tolerance.