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Kennedy Trust Prize Studentships

Project Outline

With extension of the average lifespan, the ageing population has become a heavy burden for both society and individuals. Immune responses, key for the removal of pathogens and damage, are compromised in the elderly, making the elderly more susceptible to infections. In addition immune senescence is a risk factor for many late-onset diseases, such as cancer and atherosclerosis. Autophagy through degrading bulk cytoplasmic material maintains cytoplasmic health and cellular homeostasis [1]. We have found that it allows differentiation of immune cells [2] [3]. In previous work we showed that loss of autophagy in macrophages results in low-grade inflammation (inflamm-aging) and reduces innate and adaptive immune responses, typical of a senescent immune system. Autophagy induction rejuvenates immune responses in the elderly in T cells [3]. We have recently uncovered a novel pathway that controls the translation of autophagy proteins in T and B lymphocytes. Lymphocytes from old mice and elderly humans have reduced expression of key molecules in this pathway, making it a novel aging pathway. In this project we will further define its molecular signaling elements using a variety of techniques including 18-parameter flow cytometry, transcriptomics, ribosome profiling, Image Stream, confocal microscopy, transgenic mouse models and microbiota metabolite profiling. As a druggable pathway, it will pave the way for the development of a novel mTOR independent drug that is capable of modulating autophagy.

Environment

The Kennedy Institute is a world-renowned research centre, housed in a brand new, state-of-the-art facility at the University of Oxford. The Simon lab consists of 3 postdocs, 2 DPhils students in their final year and 2 DPhil students who started in October 2017. We regularly welcome MSC students and other short-term students in the lab, so there will be opportunities to train your supervision skills. It is a small, friendly and very international lab. Even though lab members are ambitious, internally, the attitude is not competitive. Team members are encouraged to help each other out. Every DPhil student trained so far in the lab has had the opportunity to write a review, and has published a first author paper. We collaborate locally, nationally and internationally. The presentation of data at national and international conferences is strongly encouraged.

Training

A core curriculum of lectures will be taken in the first term to provide a solid foundation in a broad range of subjects including inflammation, epigenetics, translational immunology and data analysis.

Students will attend weekly seminars within the department and those relevant in the wider University. Students will be expected to present data regularly to the department and to the Simon group in lab meetings. 

References

  1. Zhang, H., D.J. Puleston, and A.K. Simon, Autophagy and Immune Senescence. Trends Mol Med, 2016. 22(8): p. 671-86
  2. Riffelmacher, T., A. Clarke, F. Richter, A. Stranks, S. Pandey, S. Danielli, . . . A. Simon, Autophagy-dependent generation of free fatty acids is critical for normal neutrophil differentiation. Immunity, 2017. in press
  3. Puleston, D.J., H. Zhang, T.J. Powell, E. Lipina, S. Sims, I. Panse, . . . A.K. Simon, Autophagy is a critical regulator of memory CD8(+) T cell formation. Elife, 2014. 3.PMC4225493

Further information 

Please contact Professor Katja Simon if you would like to enquire about the project or discuss other aspects of your application. 

Themes

  • Immunology, Ageing, Developmental Biology and Stem Cells, Molecular, Cell and Systems Biology

Project reference number #201809

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