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Dr P Paszek, Prof Mark Travis
Applications accepted all year round
About the Project
Our immune system must be able to rapidly fight against pathogens, but at the same time be tightly regulated to prevent harmful autoimmune and allergic responses. This intricate balance is controlled by specialised cells of the immune system called T cells, whose function is to orchestrate and resolve immune responses. Therapies targeting T cells have the potential to revolutionise the way we treat inflammatory disease. However, before this is achieved a better quantitative understanding of molecular processes controlling the functions of these cells is essential.
A hallmark of the T-cell activation and signalling is the production of Interleukin 2 (IL-2). Expression of this cytokine is tightly regulated by a family of transcription factors called Nuclear Factor kappaB (NF-kB). Using live-cell imaging we previously showed that in response to cytokine stimulation NF-kB undergoes nuclear-to-cytoplasmic oscillations, which control downstream gene expression (Ashall et al., Science, 2009). However the function of these dynamics in controlling IL-2 expression and T-cell signalling is still not resolved.
The aim of this project is to provide a better understanding of the molecular networks that control T-cell activation, signalling and function. We will use a multidisciplinary system biology approach involving cutting-edge live-cell-imaging, molecular cell biology, immunology and mathematical modelling (Paszek et al., PNAS, 2010). A new single-cell picture of T cell regulation will move us towards better therapeutic strategies for inflammatory disease.
Training in immunology, live-cell imaging, molecular cell biology and systems biology approaches will be provided to fit student’s background and interests.
A hallmark of the T-cell activation and signalling is the production of Interleukin 2 (IL-2). Expression of this cytokine is tightly regulated by a family of transcription factors called Nuclear Factor kappaB (NF-kB). Using live-cell imaging we previously showed that in response to cytokine stimulation NF-kB undergoes nuclear-to-cytoplasmic oscillations, which control downstream gene expression (Ashall et al., Science, 2009). However the function of these dynamics in controlling IL-2 expression and T-cell signalling is still not resolved.
The aim of this project is to provide a better understanding of the molecular networks that control T-cell activation, signalling and function. We will use a multidisciplinary system biology approach involving cutting-edge live-cell-imaging, molecular cell biology, immunology and mathematical modelling (Paszek et al., PNAS, 2010). A new single-cell picture of T cell regulation will move us towards better therapeutic strategies for inflammatory disease.
Training in immunology, live-cell imaging, molecular cell biology and systems biology approaches will be provided to fit student’s background and interests.
Funding Notes
This studentship is available to UK and other EU nationals (due to funding criteria) and provides fees and stipend subject to eligibility. Applicants should hold (or be about to obtain) a first or upper seond class honours degree in a related area.
To apply for this studentship please see: http://www.ls.manchester.ac.uk/phdprogrammes
To apply for this studentship please see: http://www.ls.manchester.ac.uk/phdprogrammes
References
Paszek P., S. Ryan, L. Ashall, K. Sillitoe, C.V. Harper, D.G. Spiller, D.A. Rand, and M.R.H White (2010). Population Robustness Arising From Cellular Heterogeneity. Proceedings of the National Academy of Sciences USA, 107: 11644-11649
*Ashall L., *C.A. Horton, *D.E. Nelson, *P. Paszek, C.V. Harper, K. Sillitoe, S. Ryan, D.G. Spiller, J.F. Unitt, D.S. Broomhead, D.B. Kell, D.A. Rand, V. Sée, and M.R.H. White (2009) Pulsatile stimulation determines timing and specificity of NF-κB-dependent transcription. Science, 324: 242-246. * Joint first authors
*Ashall L., *C.A. Horton, *D.E. Nelson, *P. Paszek, C.V. Harper, K. Sillitoe, S. Ryan, D.G. Spiller, J.F. Unitt, D.S. Broomhead, D.B. Kell, D.A. Rand, V. Sée, and M.R.H. White (2009) Pulsatile stimulation determines timing and specificity of NF-κB-dependent transcription. Science, 324: 242-246. * Joint first authors
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