Autophagy’s role in the formation or maintenance of memory T cells

Project Overview

Autophagy is a conserved pathway that delivers unwanted bulk cytoplasmic material to the lysosome. We have previously shown that the memory CD8+ T cell pool cannot form without autophagy [1]. Memory T cells are required for efficient vaccination, and in the elderly where we demonstrated that autophagy levels are low in CD8+ T cells [2], it is well known that vaccination is ineffective. When we boost autophagy levels in the elderly, the T cell memory response to influenza is restored [1]. It is not clear whether it is the maintenance or the formation/differentiation of memory T cells that requires autophagy. In this project we will address both hypotheses while also addressing the molecular mechanism. Memory T cells are quiescent and long-lived and the maintenance of that cellular lifestyle is thought to require autophagy, as our work in hematopoietic stem cells suggests [3]. Rarely dividing cells have been proposed to have less opportunity to dilute damaged cytoplasmic material to their daughter cells, however, this has not been proven. On the other hand, we know that autophagy affects differentiation of various cell types including red blood cells [4] [5], but here again, the mechanism remains largely unclear. To address these questions we will use established in vivo models as well as generate new models, and combine biochemical and "omics" techniques with high-resolution imaging and flow cytometry approaches. Our lab is funded by a Wellcome Trust investigator award and includes 3 postdocs, 1 RA and 2 DPhil students. We have moved to the Kennedy Institute of Rheumatology (KIR) in 2016. The KIR recently re-settled in Oxford to a new building on the Churchill hospital site and is now under the directorship of Fiona Powrie with a research focus on inflammation. The KIR hosts its own state-of-the-art facilities, which will be used in this project. We will also continue to draw on other Oxford-based technologies as well as on the expertise of our local, national and international collaborators.

Relevant Publications

1. Puleston, D.J., et al., Elife, 2014. 3. 
2. Phadwal, K., et al., Autophagy, 2012. 8(4). 
3. Mortensen, M., et al., J Exp Med, 2011. 208(3): p. 455-67. 
4. Mortensen, M., et al., Proc Natl Acad Sci U S A, 2010. 107(2): p. 832-7. 
5. Mizushima, N. and B. Levine, Nat Cell Biol, 2010. 12(9): p. 823-30.

Further information

Professor Katja Simon, Kennedy Institute, University of Oxford
Katja.simon@kennedy.ox.ac.uk

Please also consult the lab's website.