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The role of transcription factor SATB1 in T-cell differentiation and establishment of immune tolerance.
Department of Molecular Immunology, Toho University School of Medicine, Ohmori-nishi 5-21-16, Ohta-ku, Tokyo 143-8540, Japan
Motonari Kondo, Taku Kuwabara, Yuriko Tanaka, Taku Naito
Type of Research Project
- Basic science
What is the background of the project?
Description: Immune system is essential to protect our bodies from various pathogens as well as cancers. The principle that is central for the immune system to work is self/non-self discrimination implemented during and after lymphocyte differentiation, and cytokines play important role in executing and controlling the processes. Compromise of this principle leads to various diseases including autoimmune disorder, inflammatory diseases and cancers. We are interested in the molecular mechanism that ensures self-tolerance, i.e. c/o WMA B.P, 63,01212 Ferney-Voltaire CDEX ?FRANCE Tel. +33 (450) 04 47 59 Fax. +33 (450) 40 59 37 www.ifmsa.org 2 immune-unresponsiveness towards
What is the aim of the project?
We have found that mice lacking SATB1, a transcription factor highly expressed in T-cell lineage, develop autoimmune disorders. Our aim is to dissect the events leading to autoimmune manifestation in SATB1 knockout mice, and to understand the molecular mechanism underlying the phenotype. Ultimately, we hope to identify a novel point-of- intervention that will lead to the development of an effective therapy to autoimmune disease in the future.
What techniques and methods are used?
Our research heavily relies on the use of flow cytometer and fluorescence activated cell sorter (FACS) to analyze and isolate mouse primary cells as well as cultured cells. Cell culture is frequently performed. In addition, commonly used techniques such as RT-PCR, DNA cloning, and Western blotting are also used.
What is the role of the student?
What are the tasks expected to be accomplished by the student?
Student will be given a small project of his/her own that will be integrated in the major project of the lab, and will perform experiments to test the working hypothesis. S/he will be expected to have a logical-thinking and independent mindset with active-learning attitude to establish, support, and extend his/her idea.
Will there be any theoretical teaching provided (preliminary readings, lectures, courses, seminars etc)
Students are recommended to read several research articles and reviews prior to participate in the project. Brief lectures will be given at the start and the end of the project.
What is expected from the student at the end of the research exchange? What will be the general outcome of the student?
- The student will prepare a presentation
What skills are required of the student? Is there any special knowledge or a certain level of studies needed?
There is no prerequisite skill to participate in the project. However, knowledge on basic cell biology and molecular biology is essential. Knowledge on immunology is not necessary but preferred. Strong interest in understanding the principle underlying biological system is desired.
Are there any legal limitations in the student’s involvement
Type of students accepted
This project accepts: - Medical students - Graduated students (less than 6 months) - Pre-Medical students from the American-British system - Students in biomedical fields
- Kondo M et al. (2015) SATB1 plays a critical role in establishment of immune tolerance. J. Immunol. in press
- Guo X; Tanaka Y; Kondo M. (2015) Thymic precursors of TCR
- Satoh Y et al. (2013) The Satb1 protein directs hematopoietic stem cell differentiation toward lymphoid lineages. Immunity 38:1105-15.
- Lai AY et al. (2009) Pertussis toxin-sensitive G proteins regulate lymphoid lineage specification in multipotent hematopoietic progenitors. Blood 113:5757-64.
- Kikuchi K et al. (2008) IL-7 specifies B cell fate at the common lymphoid progenitor to pre-proB transition stage by maintaining early B cell factor expression. J Immunol. 181:383-92.
- Hsu CL; Kikuchi K; Kondo M. (2007) Activation of mitogen-activated protein kinase kinase (MEK)/extracellular signal regulated kinase (ERK) signaling pathway is involved in myeloid lineage commitment. Blood. 110:1420-8.
- Kondo M; et al. (2000) Cell-fate conversion of lymphoid-committed progenitors by instructive actions of cytokines. Nature 407:383-6.
- Kondo M; Weissman IL; Akashi K. (1997) Identification of clonogenic common lymphoid progenitors in mouse bone marrow. Cell 91:661-72.
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