The landscape and mechanisms of self-antigen splicing in thymic epithelial cells at single-cell (360G-Wellcome-105276_Z_14_A)

£29,685

Thymic epithelial cells (TECs) are essential to avert autoimmunity through their ability to promiscuously express virtually the entire gene repertoire as a molecular library against which immature T cells are selected. Whether this process generates splice isoforms unique to TECs or identical to those found in the conforming peripheral tissues remains unknown. Similarly, it is not defined whether splice variants in TECs are generated by a splicing machinery common between TEC or, alternatively, by stochastic expression of splicing factors (SFs) in individual TEC. I therefore aim to describe first the TEC transcriptome at single-cell resolution, determine the number of isoforms per gene and compare their architecture to that of a peripheral tissue. Secondly, I seek to understand how this splicing landscape is achieved and suggest a mechanistic model for alternative splicing in TECs. Moreover, possible associations of specific SFs with differences in the splicing pattern will be analyzed in single TECs. Finally, I will directly test individual components of the proposed model in vivo by generating TEC-targeted loss-offunction mutations in mice that will be monitored for their competence to establish T cell tolerance.

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Grant Details

Amount Awarded 29685
Applicant Surname Jansen
Approval Committee Internal Decision Panel for C&S
Award Date 2016-09-30T00:00:00+00:00
Financial Year 2015/16
Grant Programme: Title PhD Studentship (Basic)
Internal ID 105276/Z/14/A
Lead Applicant Miss Kathrin Jansen
Partnership Value 29685
Planned Dates: End Date 2019-01-31T00:00:00+00:00
Planned Dates: Start Date 2014-10-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region South East
Sponsor(s) Prof Jonathan Flint