SYBILLA (Systemsbiology on T-cell activation in health
SYBILLA, systems biology of T-cell activation in health and disease,
is a European Union-funded large integrated project in framework
program 7 (FP7). It is funded for 5 years with 11.1 mio Euro and started
in April 2008. It has 14 scientific and 3 industrial partners from 11
countries, lead by Dr. Wolfgang Schamel, Max Planck-Institute for
Immunobiology, Freiburg, Germany, as the scientific coordinator.
The goal of SYBILLA is to understand the intracellular signalling
network of T cells that determines T cell fate.
"Every part is reciprocally both
end and means. In such a product nothing is in vain, without an end,
or to be ascribed to a blind mechanism of nature."
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
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 of the SYBILLA consortium will be posted here in the future.
kick-off meeting, Heidelberg, 3rd May 2008
Involved in the SYBILLA project are:
- partners, that perform research and manage the consortium,
- external advisors as the scientific advisory board (SAB),
the project ethics committee (PEC) and the industrial liaison council (ILC)
- supporters as the signal transduction society (STS), the immunological
genome project (ImmGen) and Immune Response Consortium (IRC).
Schamel, Wolfgang & Reth, Michael
Max Planck Institute for Immunobiology, Freiburg, D
Expertise: biochemistry & modelling
Schamel's group uses modern biochemical approaches to understand the early
steps of T cell activation. The scientific interest is centered around the molecular
mechanism of how the TCR transmits information across the membrane.
Michael Reth's department is expert in the reconstitution of small signalling modules in
Drosophila cells in a synthetic biology approach. In addition, the group works on BCR
signalling and B cell development.
Sir Williams Dunn School of Pathology, Oxford (UK)
Molecular characterisation of TCR proximal signalling: interactome and phosphoproteome.
We use quantitative mass spectrometry and infrared imaging to characterise the dynamics and
stoichiometry of TCR signalling.
Weatherall Institute of Molecular Medicine, Oxford (UK)
Expertise: Clinical investigation
My group is focussed on the inter-phase between clinical and laboratory work,
where the clinical and molecular neuroimmunology is particularly strong.
In particlaur, we are interested in the autoimmune disease multiple sclerosis.
Centro Biologia Molecular, CSIC, Madrid (E)
Leading a group of 14 researchers dedicated to the study of the TCR in
regard to organization in the membrane, mechanisms for signal
transmission across the membrane and organization of a TCR signalosome.
The technical expertise of the group is focused towards the use of
biochemical techniques, confocal and electron microscopy and gene
expression in bone marrow precursors.
Dept. Medical Genetics, Medical University, Innsbruck (A)
The major research topic relates to the biochemical, molecular and functional analysis of signal transducing
AGC-protein S/T kinases in order to understand the (patho)physiology of T lymphocytes. The underlying
goal of the work is to understand their selective functions in signal transduction pathways in lymphocytes
and to use this information to develop strategies to manipulate the immune response, either for immunosuppression
in autoimmune diseases, graft rejection as well as the inflammatory response or for augmentation in cancer.
To achieve these aims we apply modern biochemical, molecular, cellular and mouse genetic approaches.
Aebersold, Ruedi & Gstaiger, Matthis
Institute for Molecular Systemsbiology, ETH-Zürich (CH)
A major focus in our lab is the systematic and quantitative analysis
of intracellular information processing using mass spectrometry based
approaches. We develop and apply new technologies to quantitatively
resolve the spatio-temporal organization of proteins into complexes
and signaling networks.
Our research is focused on the development and the application of mass
spectrometry (MS) based methods. Recent advances from the group
include the development of chemical reagents for quantitative mass
spectrometry, the development of a suite of software tools for the
computational analysis of proteomics data and a quantitative MS based
approach to the analysis of protein complexes.
DKFZ, BioQuant, Heidelberg (D)
Our group develops experimentally-based mathematical models for the dynamics of regulatory networks that
govern proliferation and differentiation decisions in eukaryotic cells. We investigate processes at several
levels of spatio-temporal organization, ranging from macromolecular machines in gene regulation to intra-
and intercellular signaling networks, focusing on T lymphocytes. Cell-biological problems are addressed
with a common modeling and simulation methodology, drawing on biochemical systems theory, nonlinear dynamics,
stochastic processes, reaction-transport theory, and statistical concepts for model identification.
Turku Centre for Biotechnology, University of Turkr (FIN)
Expertise: transcriptomics & modelling
We are interested in elucidating the molecular mechanisms of immune mediated human diseases.
The selective activation of functionally distinct subsets of human CD4+ lymphocytes plays an
important role in the pathogenesis of allergy and inflammatory diseases. Cytokine network
selectively regulates the development and differentiation of lymphocytes to Th1 or Th2 subsets
with restricted profile of cytokine production. Our studies aim at identification of key factors
and molecular mechanisms of lymphocyte differentiation and activation in relation to human disease.
Malissen, Marie & Malissen, Bernard
Centre d'Immunologie INSERM-CNRS, Marseille-Luminy (F)
Expertise: animal models
Our group has extensive experience and a record of contributions to the following fields:
(1) genetic analysis of the components of the T cell receptor transduction cassette;
(2) molecular basis of T cell development and T cell physiology;
(3) identification of genes associated with T cell and dendritic cell functions.
Using knock-in/knock-out approaches this group has systematically dissected the proximal
elements of the TCR transduction cassette (CD3, Lck, ZAP-70, LAT). Bernard Malissen also
supervises the IBISA Platform for Immunophenomics that comprises a "fast-track assembly
line" to engineer innovative knock-in mouse model devoted to the analysis of the complexity
of the immune system under normal and pathological conditions.
Department of Biomedicine, University Hospital Basel (CH)
Expertise: T-cell biology
The Laboratory has an extensive experience with OT-I T-cells, OT-I transgenic mice
and ligands for this TCR. It has expertise in the TCR signals leading to T-cell tolerance,
T-cell activation, AICD, and the development of memory T-cells. The group has a great deal
of knowledge regarding the effect of ligand affinity on TCR signalling and has described
how the Ras signalling components are compartmentalised in thymocytes during thymic selection.
Schraven, Burkhart & Lindquist, Jonathan
Institute of Molec & Clinical Immunology, University of Magdeburg (D)
Expertise: biochemistry & modelling
Our group has been actively involved in establishing a qualitative model describing the
signalling network organised by the TCR/CD3 complex, the co-receptors CD4/CD8 and the
costimulatory molecule CD28. Additionally, we are experts in the field of T-cell activation,
particularly in the analysis of transmembrane adaptors, proteins which serve as scaffolds
for organising the formation of signalling complexes at the membrane.
Fondazione Humanitas per la Ricerca, Padova (I)
My group studies signals modulating the immune response in physiopathological conditions.
We try to understand how to help lymphocytes to fight cancer or viruses on the one side, and,
on the other, how to block improper lymphocyte activation and thus autoimmune diseases.
In particular my group works on Cell migration, T cell priming and T cell effector functions.
Harvard Medical School & Immune Disease Institute, Boston (USA)
Internat. Centre for Genetic Engineering & Biotechnology, Delhi (IND)
Mathis, Diane & Benoist, Christophe
Joslin Diabetes Center, Harvard Medical School, Boston (USA)
Medicel, Bioinformatics Company, Espoo (FIN)
Expertise: data management
We develop an integrative data warehouse platform and provide it for the use of Sybilla.
Here the Sybilla members can put their data and integrate it to the preexisting knowledge
and begin to extract novel knowledge form their measurement and/or modelling data.
EXBIO Praha, Antibody-producing Company, Vestec (CZ)
Expertise: antibody development
EXBIO Praha - Dedicated to Superior Cytometry Reagents
We are the progressive company focused on the design, development, manufacture and
sales of high quality monoclonal antibodies for research and clinical diagnosis.
We strive to provide the complex offer of services and products for the field of
analytical cytometry, including analysis of cell signaling events.
Acies, Research Promotion and Managing Company, Lyon (F)
Expertise: Project management, use, exploitation
ACIES advises and assists players in Research and Innovation in the promotion of their
projects at economic, scientific and society level.
On the basis of an innovative management system and in-depth knowledge of the elements
at stake and the major players in Research, ACIES' skills are deployed via two activities:
Financing of Research and Innovation
Management of research networks and projects
ACIES is an example of European excellence in the management of complex and large-scale
European research projects. This SME will apply its leadership and quality management
systems to the field of research management, providing proven and specialised
procedures to the members of the SYBILLA consortium. ACIES will also coordinate
the IPR Committee and will thus ensure an efficient and relevant use and
exploitation of the project results.
Scientific advisory board (SAB)
The SAB is composed of external experts recognised for their
expertise in the field of the project:
- Dr. Leroy Hood, Institute for Systems Biology, Seattle, USA
- Dr. Arup Chakraborty, Massachusetts Institute of Technology, MIT, Cambridge, USA
- Dr. Carola Vinuesa, Australian National University, Canberra, Australia
- Dr. Alastair Compston, University of Cambridge, UK
- Dr. Arthur Weiss, University of California, San Francisco, UCSF, USA
- Dr. Alexander Rudensky, University of Washington, Seattle, USA
Project ethics committee (PEC)
The role of the PEC will be to review the ethical aspects of the research
activities carried out in the project.
- Dr. Vladimir Viklicky, Prague, Czech Republic
- Dr. Carlos Alonso, Madrid, Spain
- Dr. Wolfgang Schamel, Freiburg, Germany
Industrial liaison council (ILC)
The ILC is composed of large industrialists with strong interests in
the activities conducted within the project.
- Novartis, Switzerland
- Boehringer Ingelheim, Germany
- Novo Nordisk A/S, Denmark
The Signal Transduction Society
The Signal Transduction Society (STS) is devoted to
scientific exchange between investigators concerned with cellular
signal transduction. Therefore, it supports SYBILLA in the dissemination
of research as well as in the organization of meetings.
The Immunological Genome Project
The Immunological Genome Project (ImmGen) generates a complete
microarray dissection of gene expression in the mouse immune system.
Therefore, it is complementary to SYBILLA. Joint activities are planned.
Immune Response Consortium (IRC) (USA)
The Immune Response Consortium (IRC) is a US-based
consortium that models biological networks.
Here you can download PDF and powerpoint documents that present
SYBILLA as well as press releases related to SYBILLA.
- A short description of the SYBILLA project for the general
audience: general public.
- A short description of the SYBILLA project for the scientific audience:
- A 10 min presentation of SYBILLA by Wolfgang Schamel
on the 22nd August 2008 at the International Conference on
Systems Biology (ICSB 2008) in Göteborg,
Sweden: Göteborg 2008.
SYBILLA is also devoted to teaching activities.
within the consortium in order to teach standardized,
robust techniques and
(ii) seminars for a wide scientific audience.
Bioinformatics, 22nd - 24th September 2008, Espoo, Finland
Partner MEDICEL has successfully performed a workshop on bio-informatics,
including data integration into MEDICEL data warehouse, integration of
isolated data banks with various biological information such as DNA, mRNA,
protein. 14 scientists participated and the workshop materials are available
on the MEDICEL website.
Transcriptomics, November/December 2008, Turku, Finland
Partner UTU will offer a workshop on transcriptomics in the analysis of
human T-cell differentiation and function.
Standardized Biotechniques, February/March 2008, Freiburg, Germany
will provide a compulsory workshop for SYBILLA partners
that teaches the use of standardised cell biology and biochemistry protocols.
Proteomics, February/March 2008, Zürich, Switzerland
will provide a training session on quantitative proteomics
using mass spectroscopy.
Management, February 2008, Lyon, France
Partner ACIES offers a focussed training of management activities for
large consortia, reporting FP7 projects to the EU and ethics in conducting
Systems Biology, March/April 2008, Heidelberg, Germany
Partner DKFZ plans to perform a workshop for training in (1) methods of
mathematical modelling & data analysis aimed at experimentalists, (2)
immunology and cell biology aimed at theoreticians, (3) research workshop
on inter-action of experiment and theory.
Seminars, workshops and conferences for the public will be announced here in time.
Kick-off meeting, M0
The SYBILLA kick-off meeting successfully took place in Heidelberg,
Germany, on the 2nd and 3rd May 2008. The organization was done by
Thomas Höfer (DKFZ), Caroline Carbonelle (ACIES) and Wolfgang Schamel
kick-off meeting, Heidelberg, 3rd May 2008
Strategical meeting, M6
The Executive Management Committee and Governing Board meetings successfully
took place in Madrid, Spain, on the 22nd and 23rd October 2008. The
organization was done by Balbino Alarcon (CSIC), Caroline Carbonelle (ACIES)
and Wolfgang Schamel (MPI-IB).
Strategical meeting, M12
The Executive Management Committee and Governing Board meetings will take
place in Sardinia, Italy.
General comments and suggestions
Suggest a new protein to include into the interactome project
Suggestions for cooperation with SYBILLA.
SYBILLA offers attractive, interdisciplinary Postdoc and PhD student
positions at different locations, involving different projects.
For further information please contact ACIES:
PD Dr. Wolfgang Schamel
Dept. of Molecular Immunology
Max Planck-Institute for Immunobiology
Dr. Caroline Carbonelle
69 rue de la Republique