System Biology and Immune Response

Transcription

1 System Biology and Immune Response Fondation Mérieux Conference Centre Les Pensières Veyrier-du-Lac - France June 21-23, 2010 Steering Committee: Nicolas BURDIN Bruno GUY Michael KATZE Jacques LOUIS Ray OOMEN Bali PULENDRAN Coordination: Katia MIELCZAREK C 100 M 72 J0 N 32 Pantone : 281 C

2 Background Despite great progress in the ability to measure parameters of the immune response with sensitivity and precision, the very complexity of the immune system presents a barrier to understanding how protective immunity can be generated to the vast spectrum of pathogens, or how its role in physiological health may be compromised, leading to cancers or chronic disease. Following on a century of brilliant reductionist science, our current picture of the immune system, as a system, can be likened to an incomplete engineering diagram, where some modules and individual components are understood in greater or lesser detail, while others are known to be missing, and connections between them are only roughly sketched in. Unlike pharmaceutical research, where a target may be a specific molecular entity, vaccine research must target an integrated complex system organized at multiple levels: from the molecular and cellular, to tissues, organs, individuals, and populations. Today, as we recognize the need to induce immune responses that go beyond the ability to generate protective antibody, we are confronted with a constellation of sentinel systems, receptor and signaling pathways and specialized cell types interacting in tissue-specific ways, and which must somehow collectively learn how to protect our bodies from pathogens which, in many cases, have insinuated themselves into the inner workings of our immune response mechanisms. Today, high-throughput technologies can extend our understanding of the immune system by collecting vast amounts of data on complete functioning systems at many levels of biological complexity. When referenced against the genomes of host systems and pathogens, there is hope that comprehensive descriptions of system behaviour can ultimately be obtained. There is already evidence that sufficiently comprehensive data sets can expand our awareness of the immune response and identify pivotal regulatory genes. Coupled with appropriate modelling techniques, these early findings suggest that reasonably accurate predictions of immunological behaviour may be possible in the future. The objective of this conference is to look at how systems-based studies can facilitate our understanding in a number of areas relevant to the immune system and vaccinology, including: how immune responses are shaped in response to different stimuli, how different portals of entry (intra-nasal, intra-muscular, mucosal versus respiratory) influence the functional repertoire of available immune responses, how host and pathogen responses evolve in real time, in relation to each other, whether markers that are diagnostic of desirable or undesirable immune responses can be found and new correlates of vaccine efficacy uncovered, how populations of different pathogens and host cell types interact to give rise to emergent properties such as protection and immunopathology. Each speaker has been asked to specifically address one or more of these objectives in their presentation. There will be a professionally prepared report of the Conference s presentations and discussions including specific responses to the above objectives.

3 Monday 21 June Registration Welcome Address Alain MERIEUX Keynote lecture: Systems Biology and Translational Medicine Elias ZERHOUNI Welcome dinner Tuesday 22 June 2010 Session 1 Experimental technologies to support system biology Chaired by Ray Oomen Mapping and Quantifying Transcriptomes by RNA-seq. Barbara WOLD Discussion Imaging the Immune System at Work Ronald GERMAIN Discussion Coffee break Multiparameter Phosphoprotein Analysis in Single Cells by Flow Cytometry Garry NOLAN Discussion Host cell interactomes of bacterial proteins Steffen BACKERT Discussion Selected Reaction Monitoring Assays for Proteomes Ralph SCHIESS Discussion

4 Mice from the collaborative Cross project: a new tool for systems biology approach Ralph BARIC Discussion Lunch Session 2 Informatics: data integration, visualization, interpretation Chaired by Bruno Guy & Fiona Brinkman System-level analyses of Innate Immunity Fiona BRINKMAN Discussion Towards Genome Scale Signaling Network Reconstructions Daniel HYDUKE Discussion Interactive Modelling of Multicellular Immune Networks Irun COHEN Discussion Coffee break Reconstructing innate immune and host-pathogen networks Nir HACOHEN Discussion The Immunological Genome Project Christophe BENOIST Discussion Random Insertional Mutagenesis (ENU) in mice Emilie NARNI-MANCINELLI Discussion Dinner

5 Wednesday 23 June 2010 Session 3 System Biology of host-pathogens Interactions Chaired by Luigi Buonaguro & Michael Katze Whole-Tissue Gene Expression and Host Response Ray OOMEN Discussion Viral Infections and Host Response Michael KATZE Discussion Primate models for a systems biology approach to understanding SIV infection Michaela MÜLLER-TRUTWIN Discussion Coffee break Molecular signatures of HIV-1 vaccines Luigi BUONAGURO Discussion Evolutionary conserved Herpes viral protein interaction network Juergen HAAS Discussion Session 4 System Biology and Applied Immunology/Vaccinology Chaired by Nicolas Burdin & Bali Pulendran Predictive power of system biology for vaccinology Bali PULENDRAN Discussion Lunch

6 Transcriptional and cellular signatures of vaccine adjuvants Ennio DE GREGORIO Discussion Identification of blood transcriptional signatures in active pulmonary tuberculosis Anne O GARRA Discussion Conclusion and end of the meeting Coffee before departure