Grant: Catalyst Grant: Systems Biology Approaches to Immunotherapy

Phosphorylation-mediated signal transduction is a mechanism for regulation of host cell processes, including infection and immunity. Global characterization of signal transduction, particularly for species outside the research mainstream, is currently limited by the absence of research tools. This is problematic as many of these species provide relevant models of human disease. Global kinome analysis would greatly enhance the value of these animal models at a systems level and ensure efficient knowledge translation to clinical applications. To address this deficiency our lab has developed a methodology, based on genomic information, to create species-specific peptide arrays for global analysis of kinome responses. In this proposal, in collaboration with Dr. Brinkman, we will capitalize on the potential of these arrays to provide a systems biology perspective on processes relating to infection and immunity. Through creation of InnateDB, her lab has expertise in mapping pathways and processes of immune responses. Layering signal transduction information onto this existing framework will significantly increase the value of this publically available resource. Specifically, we will develop and apply peptide arrays to the analysis of porcine and human monocyte responses to stimuli which reflect defined components of viral and bacterial infections. The pig is an important model of human bacterial and viral infection and understanding dynamic patterns of phosphorylation-mediated signal transduction in response to these stimuli will provide valuable insights into mechanisms of immunity, conservation of responses across species, validation of animal models of disease and research translation to clinical applications. From a broader perspective this will provide a framework for development of species-specific customized arrays to better understand conservation of cellular responses across species and more detailed insight into the cellular mechanisms of disease.