CISBIC Sub-project 2: Spatio-temporal Control of Phagocytic Signalling During Uptake of Attenuated Salmonella typhimurium
Recognition and uptake of bacteria, parasites and encapsulated DNA vaccines by professional phagocytes - macrophages, dendritic cells - is crucial for the induction of protective immunity, through cytokine release and processing and presentation of antigens for recognition by the adaptive immune system. Live attenuated strains of intracellular pathogens such as Salmonella and Shigella have been shown to act as oral human and animal vaccines and as heterologous vaccine carriers capable of inducing protective responses to antigens from other viral, bacterial and eukaryotic pathogens.
The mechanism of attenuation is crucial in determining vaccine efficacy, but the biology of this is unknown; in practice multiple mutants are screened in an empirical trial and error manner. It would be a major scientific advance to be able to engineer improved vaccine strains on the basis of a rational understanding of the factors that determine their ability to stimulate a protective, lasting immune response. This may now be possible through a systems biology approach that can directly inform on logical targets for mutagenesis studies. Because interaction with innate immune cells is central to immunogenicity, in this sub-project we will study the early stages of phagocytosis of attenuated Salmonella typhimurium and develop predictive models that will assist in design of improved human and animal vaccines.
Organisms:
- Salmonella typhimurium
Funding:
- BBSRC Research Grant:
Affiliates:
For more information about the outputs from this project or to discuss data reuse please contact bsshelp@imperial.ac.uk
CISBIC Sub-project 2
- Dr Robert Endres
- Dr Emmanuelle Caron
- Dr George Tzircotis (biology)
- Dr Ozan Kahramanoğulları (modelling)
- Dr Jeroen van Zon (modelling)
- Dr Anna Dart (biology)
- Dr Sylvain Tollis (modelling)
- Dr Amir Horowitz (biology)
- Dr Martin Spitaler (core facility)
- Dr Vania Braga (biology)
- Dr Martin Howard (modelling)
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- (Tollis)
MATLAB code for the analysis of microscopy images of bacterial phagocytosis
- (Tollis)
Surface Evolver code for the simulation of bacterial phagocytosis
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Compositional process algebra models of actin polymerisation and a geometric representation of these models that allows movies to be generated reflecting their dynamics
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PIM model and corresponding SPiM representation of Fcγ receptor phosphorylation during phagocytosis (from http://dx.doi.org/10.4204/EPTCS.9.9)
- (Dart)
Zeiss LSM imaging of bacterial phagocytosis
- (Tzircotis)
Zeiss LSM imaging of bacterial phagocytosis
- (Tollis)
AVI visualisation of 3D simulation of phagocytic engulfment
Articles:
-
van Zon JS, Tzircotis G, Caron E, Howard M.
Mol Syst Biol. 2009;5:298. Epub 2009 Aug 18. -
L. Cardelli, E. Caron, P. Gardner, O. Kahramanoğulları, A. Phillips
Theoretical Computer Science 410, 3166-3185 (2009) -
O. KahramanoÄŸullari, L. Cardelli, E. Caron
Electronic Proceedings in Theoretical Computer Science 9, 73-86 (2009) -
L. Cardelli, E. Caron, P. Gardner, O. Kahramanoğulları, A. Phillips
Electronic Notes in Theoretical Computer Science 229, 127-144 (2009) -
Gurry T, KahramanoÄŸullari O, Endres RG. Biophysical mechanism for ras-nanocluster formation and signaling in plasma membrane
PLoS One. 2009 Jul 9;4(7):e6148 -
KahramanoÄŸullari O. On linear logic planning and concurrency
Information and Computation, Volume 207, Issue 11, November 2009, Pages 1229-1258 -
Tollis S, Dart AE, Tzircotis G, Endres RG.
BMC Syst Biol. 2010 Nov 8;4:149. -
Tzircotis G, Braga VM, Caron E.
J Cell Sci. 2011 Sep 1;124(Pt 17):2897-902 -
KahramanoÄŸullari O. Process Algebra Models in Biology: The Case of Phagocytosis
Systemic Approaches in Bioinformatics and Computational Systems Biology: Recent Advances (2011)
Presentations:
- Investigating Forces for Uptake and Cup Closure - The Role of Myosins in Phagocytosis (Dart, 2007)
- (Kahramanoğulları, 2007)
- Spatio-temporal control of phagocytosis (Endres, 2009)
- Understanding phagocytic receptor localisation and signalling (Tzircotis, 2009)
- Understanding phagocytic signalling (Tzircotis, 2009)
- Progress report (Caron, 2009)
- How one cell eats another - Experiments and modeling elucidate biophysical requirements for uptake (Tollis, 2010)
Experiments and modeling elucidate biophysical requirements for uptake (Tollis)
- How one cell eats another – Experiments and modelling elucidate early signalling events and biophysical requirements for uptake (Endres, 2010):
How one cell eats another - Enders - 20 May 2010
- How one cell eats another - Physical principles in phagocytic uptake (Endres, 2010)
Physical principles in phagocytic uptake
- How one cell eats another – experiments and modelling elucidate mechanism of uptake (Endres, 2010)
How one cell eats another - Enders - 6 July 2010
- How one cell eats another – Experiments and modelling elucidate early signalling events and biophysical requirements for uptake (Endres, 2010)
How one cell eats another - Enders - 7 January 2010
- How one cell eats another – Experiments and modelling elucidate early signalling events and biophysical requirements for uptake (Tollis, 2010)
New model to explain experimental data (Tollis)
- How one cell eats another – Experiments and modelling elucidate early signalling events and biophysical requirements for uptake (Endres, 2010)
How one cell eats another - Enders - 8 October 2010
- Live cell imaging of particle capturing during phagocytosis (Horowitz, 2011)
- Myosins (Dart, 2011)
Posters:
- Investigating Forces for Uptake and Cup Closure – The Role of Myosins in Phagocytosis (Dart, 2007)
Investigating Forces for Uptake and Cup Closure (Poster)
- How one cell eats another: Experiments and modelling investigate biophysical requirements for uptake (Tollis, 2010)
How one cell eats another (Poster)