|
|
Home > Research
Research Background  Saez-Rodriguez et al. 2007 PLoS Comput.Biol. The immune system has to discriminate pathogens (e.g. bacteria or viruses and cancerous cells) from healthy cells within our body. Foreign cells should be attacked and eliminated, whereas self-tissues should not be harmed. The main cell type involved in this decision is the T-cell. T-cell activation is a complex process relying on multiple layers of tightly controlled intracellular signaling molecules, which form an intricate and dynamic network. Defects in this network can cause autoimmune responses that destroy normal body cells: Horror autotoxicus. This term was coined by the bacteriologist and immunologist Paul Ehrlich (1854-1915) to describe the body's immunological self-destruction in severe disorders such as multiple sclerosis. In order to understand and predict the behaviour of this network it is therefore crucial to study it as a complete system and not only its isolated parts. Scientific concept Through a multidisciplinary effort SYBILLA aims to understand at systems level, how T-cells discriminate foreign- from self-peptides by activating quantitatively distinct signaling pathways. Data obtained in mouse models are extended to human T cells and to a mouse model of multiple sclerosis.
SYBILLA develops new analytical and mathematical tools to generate and integrate high-density quantitative data describing T-cell activation. Proteomics, transcriptomics, imaging and biochemical techniques will be applied to obtain holistic maps of the T-cell signaling network and to achieve a quantitative and dynamic understanding of signaling networks and their regulation in response to different signal inputs.
Building upon already existing schemes of the network connectivity, constant iteration between experiment and mathematical modelling will be used to develop robust and predictive models that describe the functioning of the T-cell signaling network. SYBILLA will allow the identification of new drug targets and the discovery of new biomarkers to refine prognosis of autoimmune diseases. Publications
A list of publications of the SYBILLA consortium can be seen in these tables here. Or you can downloaded them:
List of scientific publications of the SYBILLA consortium for 2012
| Title | Peer-reviewed journal | Year | Relevant pages | Pubmed | Partners involved | | T cell receptor (TCR)-induced tyrosine phosphorylation dynamics identifies THEMIS as a new TCR signalosome component. | JBC | 2011 | 7535-47 | PMID: 21189249 | Acuto O, UOXFa | | Quantitative analysis of protein phosphorylations and interactions by multi-colour IP-FCM as an input for kinetic modelling of signalling networks. | PLoS ONE | 2011 | e22928 | PMID: 21829558 | Höfer T, DKFZ Schamel W, MPI-IB | | Integrating signals from the T-cell receptor and the interleukin-2 receptor | PLoS Comput Biol | 2011 | e1002121 | PMID: 21829342 | Schraven B, Lindquist J, UNIMAG | | Increased Sensitivity of Antigen-Experienced T Cells through the Enrichment of Oligomeric T Cell Receptor Complexes. | Immunity | 2011 | 375-87 | PMID: 21903423 | Alarcon B, CSIC, Schamel W, MPI-IB | | The balance of pro-inflammatory and trophic factors in multiple sclerosis patients: effects of acute relapse and immunomodulatory treatment | Mult Scler | 2011 | 851-866 | PMID: 21561957 | Lindquist J, UNIMAG | | Molecular T cell biology?-?basic and translational challenges in the twenty-first century. | Front Immunol | 2011 | ePub | PMID: 22566794 | Acuto O, UOXFa | | LAT signaling pathology: an "autoimmune" condition without T cell self-reactivity. | Trends Immunol | 2010 | 253-259 | PMID: 20542732 | Malissen B, CNRS | | Signaling in thymic selection. | Curr Opin Immunol | 2011 | 207-212 | PMID: 21242076 | Palmer E, UNIBAS | | Quantitative proteomics analysis of the nuclear fraction of human CD4+ cells in the early phases of IL-4-induced Th2 differentiation. | Mol Cell Proteomics | 2010 | 1937-1953 | PMID: 20467038 | Lahesmaa R, UTU | | SATB1 dictates expression of multiple genes including IL-5 involved in human T helper cell differentiation. | Blood | 2010 | 1443-1453 | PMID: 20522714 | Lahesmaa R, UTU | | Structural characterization of the TCR complex by electron microscopy. | Int Immunol | 2010 | 897-903 | PMID: 21059766 | Alarcon B, CSIC, Schamel W, MPI-IB | | Genome-wide profiling of interleukin-4 and STAT6 transcription factor regulation of human Th2 cell programming. | Immunity | 2010 | 852-862 | PMID: 20620947 | Lahesmaa R, UTU | | A new vampire saga: the molecular mechanism of T cell trogocytosis. | Immunity | 2011 | 151-153 | PMID: 21867922 | Schamel W, MPI-IB | | Coronin 1A is an essential regulator of the TGFß receptor/SMAD3 signaling pathway in Th17 CD4(+) T cells. | J Autoimmun | 2011 | 198-208 | PMID: 21700422 | Baier G, MUI | | Synthetic immune signaling | Curr Opin Biotech | 2012 | 1-5 | PMID: 22326912 | Schamel W, Reth M, MPI-IB | | TCR Nanoclusters as the Framework for Transmission of Conformational Changes and Cooperativity. | Front Immunol | 2012 | ePub | PMID: 22582078 | Alarcon B, CSIC | | T cell receptor internalization from the immunological synapse is mediated by TC21 and RhoG GTPase-dependent phagocytosis. | Immunity | 2011 | 208-222 | PMID: 21820331 | Alarcon B, CSIC | | Identification of early gene expression changes during human Th17 cell differentiation. | Blood | 2012 | ePub | PMID: 22544700 | Lahesmaa R, UTU | | A discrete affinity-driven elevation of ZAP-70 kinase activity initiates negative selection. | J Recept Signal Transduct Res | 2012 | 430-443 | PMID: 20945976 | Palmer E, UNIBAS | | Meeting report signal transduction meets systems biology. | Cell Commun Signal | 2012 | ePub | PMID: 22546078 | Lindquist J, UNIMAG, Schamel W, MPI-IB | | Phosphoprotein associated with glycosphingolipid-enriched microdomains differentially modulates SRC kinase activity in brain maturation. | PLoS One | 2011 | e23978 | PMID: 21915273 | Lindquist J, Schraven B, UNIMAG | | The balance of pro-inflammatory and trophic factors in multiple sclerosis patients: effects of acute relapse and immunomodulatory treatment. | Mult Scler | 2011 | 851-866 | PMID: 21561957 | Lindquist J, UNIMAG | | Serotonin-mediated tuning of human helper T cell responsiveness to the chemokine CXCL12. | PLoS One | 2011 | e22482 | PMID: 21853036 | Viola A, FHR | | The critical role of agrin in the hematopoietic stem cell niche. | Blood | 2011 | 2733-2742 | PMID: 21653324 | Viola A, FHR | | Agrin is required for survival and function of monocytic cells. | Blood | 2012 | ePub | PMID: 22517892 | Viola A, FHR |
List of scientific
publications of the SYBILLA consortium for 2009 and 2010
|
Title
|
Journal
|
Year
|
Pages
|
Pubmed
number
|
SYBILLA
Partners
|
|
Quantitative
interaction proteomics using mass spectrometry.
|
Nat Methods
|
2009
|
203-205
|
PMID: 19198594
|
Aebersold R,
Gstaiger M. ETHZ
|
|
STAT6 deletion converts the Th2 inflammatory
pathology afflicting Lat(Y136F) mice into a lymphoproliferative disorder
involving Th1 and CD8 effector T cells.
|
J Immunol.
|
2009
|
2680-2689
|
PMID: 19234162
|
Malissen B
Malissen M CNRS
|
|
T Cell-Mediated Autoimmune Disease Due to
Low-Affinity Crossreactivity to Common Microbial Peptides.
|
Immunity
|
2009
|
348-357
|
PMID: 19303388
|
Fugger L. UOXF
|
|
PKC inhibitors: potential in T cell-dependent immune
diseases.
|
Curr Opin
Cell Biol
|
2009
|
262-267
|
PMID: 19195860
|
Baier G MUI
|
|
Loss of the LAT adaptor converts antigen responsive
T cells into pathogenic effectors that function independently of the T cell
receptor.
|
Immunity
|
2009
|
197-208
|
PMID: 19682930
|
Malissen B, CNRS
|
|
Lymphoproliferative disorders involving T helper
effector cells with defective LAT signalosomes
|
Sem
Immunopath.
|
2010
|
117-125
|
PMID: 20107804
|
Malissen B, CNRS
|
|
Signaling amplification at the immunological
synapse.
|
Current
Topics Microbiol Immunol
|
2010
|
109-122
|
PMID: 19960311
|
Viola A, FHR
|
|
Tunable chemokine production by antigen presenting
dendritic cells in response to changes in regulatory T cell frequency in
mouse reactive lymph nodes.
|
PLOSone
|
2009
|
4:e7696
|
PMID: 19893746
|
Viola A, FHR
|
|
A novel KIR-associated function: evidence that CpG
DNA uptake and shuttling to early endosomes is mediated by KIR3DL2
|
Blood
|
2010
|
1637-1647
|
PMID: 20147700
|
Viola A, FHR
|
|
Constitutively active Lck in T cell drives antigen
receptor signal transduction
|
Immunity
|
2010
|
766-777
|
PMID: 20541955
|
Viola A, FHR,
Acuto O, UOXFa, Fugger L. UOXFb,
Höfer T, DKFZ
|
|
PKC-theta Modulates the Strength of T Cell Responses
by Targeting Cbl-b for Ubiquitination & Degradation
|
Science
Signaling
|
2009
|
ra30
|
PMID: 19549985
|
Baier G. MUI
|
|
The potent protein kinase C selective inhibitor
AEB071 (Sotrastaurin)represents a new class of immunosuppressive agents
affecting early T cell activation
|
J Pharmacol
Exp Ther.
|
2009
|
792-801
|
PMID: 19491325
|
Baier G. MUI
|
|
PKC theta cooperates with PKC alpha in alloimmune
responses of T cells in vivo.
|
Mol Immunol
|
2009
|
2071-2079
|
PMID: 19356803
|
Baier G. MUI
|
|
(PKC inhibitors: potential in T cell-dependent
immune diseases
|
Curr Opin
Cell Biol.
|
2009
|
262-267
|
PMID: 19195860
|
Baier G, MUI
|
|
NFAT pulls the strings during CD4+ T helper cell
effector functions.
|
Blood
|
2010
|
2989-2997
|
PMID: 20103781
|
Baier G. MUI
|
|
SATB1 dictates expression of multiple genes
including IL-5 involved in human T helper cell differentiation
|
Blood
|
2010
|
1443-1453
|
PMID: 20522714
|
Lahesmaa R, UTU
|
|
Quantitative Proteomics Analysis of the Nuclear
Fraction of Human CD4+ Cells in the Early Phases of IL-4 Induced Th2
Differentiation
|
Molec Cell
Proteomics
|
2010
|
1937-1953
|
PMID: 20467038
|
Lahesmaa R, UTU
|
|
Analysis of novel phospho-ITAM specific antibodies
in a S2 reconstitution system for TCR-CD3 signalling
|
Imm Lett
|
2010
|
43-50
|
PMID: 20005895
|
Schamel W, MPI-IB
Suchanek M, EXBIO
|
|
Stoichiometry and intracellular fate of TRIMcontaining
TCR complexes
|
Cell Commun
Signal
|
2010
|
8:5
|
PMID: 20298603
|
Schamel W, MPI-IB
Schraven B, UNIMAG
|
|
Detection of phosphorylated T and B cell antigen
receptor species by Phos-tag SDS-and Blue Native-PAGE
|
Imm Lett
|
2010
|
51-56
|
PMID: 20005898
|
Schamel W, MPI-IB
|
|
Das
Imunsystem besser verstehen lernen
|
systembiologie.de
|
2010
|
51-55
|
|
Höfer T, DKFZ
Lindquist J, Schraven B, UNIMAG
Schamel W, MPI-IB
|
|
