Overall the fellowship was a successful endeavour and lasted a total of 15 months from the intended 24 months. I withdrew early as a result of being offered a prestigious position at Monash University in Australia, leading the Stromal Immunology research group, largely due to the work outlined in this report.
We have progressed through our milestones with effectiveness and have achieved SO1 and SO2 within the lifespan of the fellowship.
In our application, some proposed experiments were mouse-based, as we (and others) believed mouse models needed to be used to address some of our hypothesis. However, our work on human samples revealed that mechanisms in human FRCs were very different that those in mice. Therefore, we amended our plans to answer the same questions using human cells and systems, which in turn made our results more immediately applicable and has resulted in more significant outcomes. Our results can be summarized as follows:
1) We have shown that human T cell proliferation is effectively halted by human FRCs, as is activation and differentiation. This is novel.
2) We have established that human T cells are still fully functional after their encounter with FRCs and are able to activate to normal levels.
3) We found that inhibition by FRCs was induced by secreted factors as conditioned media alone is able to halt proliferation and activation.
4) We have determined 4 mechanisms that are responsible for suppression of activation of T cells by FRCs and have applied specific inhibitors for each one that partially reverse this effect but if applied together do so completely.
5) We have run RNA-sequencing for FRCs and MSCs to highlight their similarities and differences and applied that expertise in collaborations that have been recently published (Tamblyn et al. 2017 BioScientifica).
6) We have developed new assays to confirm in situ our observations and show proliferation of T cells after treatment in patient samples.
7) In recent days we have submitted our manuscript for publication that summarizes this work in a high impact journal and we are still developing further work for two more publications that will be the result of data generated by this work.
8) As a result of this fellowship I have obtained $1.3M AUD in funding and a job co-leading a laboratory, where I plan to continue the work I started with this fellowship.
Some of the work that was carried out was presented at the International Congress of Immunology (Melbourne, 2016) and an abstract published at the European Journal of Immunology (Knoblich et al. 2016). The work will also be presented at the next international T cell meeting (ThymOz, Heron Island, 2018). We have also recently submitted the work for publication (decision pending). As a result of this work I obtained a position as a Lab Head that allows me to carry on the work that was made possible by the Marie Curie fellowship. In addition, data generated during the fellowship will allow me to apply for future grants.
