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  Innate Immunity and Dendritic Cells


   London Research Institute

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  Dr C Reis e Sousa  No more applications being accepted  Funded PhD Project (Students Worldwide)

About the Project

This 4-year Crick PhD studentship is offered in Dr Caetano Reis e Sousa's Immunobiology Group based at the Cancer Research UK London Research Institute (LRI). The successful applicant will join the Crick PhD Programme in September 2015.

Research in the Immunobiology Laboratory is centred on the receptors and signalling pathways that detect changes in homeostasis (“innate immunity”) with a focus on those that ultimately promote the activation of dendritic cells (DC), resulting in adaptive immunity. DC activation can be driven by direct DC contact with potential pathogens or infected cells. We have shown that DC can utilise members of the toll-like receptor (TLRs) family, including TLR9, 7, or 3, to detect viruses and virally-infected cells. We have additionally shown that viruses can be recognised by DC and other cells via cytosolic receptors such as RIG-I, which is activated by viral RNA genomes bearing 5’ tri- or di-phosphates. Finally, we have identified a distinct pathway for DC activation by fungi mediated by C-type lectin receptors, which signal via Syk kinase. Notably, our work has also shown that the C-type lectin/Syk pathway is additionally involved in DC recognition of cell death. For example, one Syk-coupled C-type lectin, DNGR-1, binds to F-actin exposed by dead cells and signals to modulate immunity to cytopathic pathogens. Collectively, the work of the Immunobiology Laboratory helps build a global picture of the receptors and signalling pathways that regulate DC activation, with applications in immunotherapy of cancer and infectious diseases.
DC constitute a heterogeneous family and another major focus of the lab is on defining DC and the role of different types of DC in the immune system. We have identified gene products that can be used to mark DC progenitors or to distinguish different murine DC subtypes, opening the door to selective manipulation of DC and/or DC subsets in mouse models. In addition, we are characterising the human equivalents of defined mouse DC subsets and examining their potential as targets for immunotherapeutic intervention.
The precise project within these broad areas of research will depend on the interests of the successful candidate and will be defined upon discussion with the supervisor. The lab utilises a very wide variety of molecular and cellular techniques, including animal manipulation, flow cytometry, confocal microscopy, biochemistry, genetics and molecular biology. Opportunities exist for collaboration with other groups, at Crick and elsewhere.

Talented and motivated students passionate about doing research are invited to apply for this PhD position. Students who join the 2015 Crick PhD Programme, will start their PhDs at the LRI in September 2015, will register for their PhD at one of the Crick partner universities (Imperial College London, King's College London or University College London), and will transfer into the Crick with their research group in early 2016.

Applicants should hold or expect to gain a first/upper second-class honours degree or equivalent in a relevant subject and have appropriate research experience as part of, or outside of, a university degree course and/or a Masters degree in a relevant subject.
APPLICATIONS MUST BE MADE ONLINE VIA OUR WEBSITE BY 5PM GMT NOVEMBER 12TH 2014. APPLICATIONS WILL NOT BE ACCEPTED IN ANY OTHER FORMAT.
http://www.london-research-institute.org.uk/phd/


Funding Notes

Successful applicants will be awarded a non-taxable annual stipend of £22,000 plus payment of university tuition fees. Students of all nationalities are eligible to apply.

References

1. Goubau, D., M. Schlee, S. Deddouche, A.J. Pruijssers, T. Zillinger, M. Goldeck, C. Schuberth, A.G. Van der Veen, T. Fujimura, J. Rehwinkel, J.A. Iskarpatyoti, W. Barchet, J. Ludwig, T.S. Dermody, G. Hartmann, and C. Reis e Sousa. 2014. Antiviral immunity via RIG-I-mediated recognition of RNA bearing 5′-diphosphates. Nature In press.
2. Schraml, B.U., J. van Blijswijk, S. Zelenay, P.G. Whitney, A. Filby, S.E. Acton, N.C. Rogers, N. Moncaut, J. Carvajal, and C. Reis e Sousa. 2013. Genetic tracing via DNGR-1 expression history defines dendritic cells as a hematopoietic lineage. Cell 154:843-858
3. Ahrens, S., S. Zelenay, D. Sancho, P. Hanč, S. Kjær, C. Feest, G. Fletcher, C. Durkin, A. Postigo, M. Skehel, F. Batista, B. Thompson, M. Way, C. Reis e Sousa, and O. Schulz. 2012. F-actin is an evolutionarily-conserved damage-associated molecular pattern recognized by DNGR-1, a receptor for dead cells. Immunity 36:635-645.
4. Rehwinkel, J., C.P. Tan, D. Goubau, O. Schulz, A. Pichlmair, K. Bier, N. Robb, F. Vreede, W. Barclay, E. Fodor, and C. Reis e Sousa. 2010. RIG-I detects viral genomic RNA during negative-strand RNA virus infection. Cell 140:397-408.
5. Sancho, D., O. Joffre, A. Keller, N.C. Rogers, D. Martinez, P. Hernanz-Falcón, I. Rosewell, and C. Reis e Sousa. 2009. Identification of a dendritic cell receptor that couples sensing of necrosis to immunity. Nature 458:899-903.