Research Capabilities
Early, Validated Biomarkers of Infectious Diseases in Humans
The development of a 3-D cell culture platform for rapid discovery of biomarkers in host-pathogen relationships will ultimately enhance the understanding of exposure mechanisms and help in the discovery of biosignatures.
PNNL's use of three-dimensional (3-D) cell culture systems in this project provides researchers with new tools for rapidly discovering biomarkers in host-pathogen relationships. These tools aid the identification of biosignatures and enhance our understanding of exposure mechanisms. In-vitro organoid cell culture models are providing physiologically relevant insights into human infectious diseases and will aid in the rapid screening for infectious agents. While 2-D cell culturing systems have proven to be less expensive than conducting in-vivo studies using live animals, and also have provided opportunities for numerous replications, rapid screening and simultaneous testing under a variety of conditions, they have often failed to produce adequate results when pathogenic organisms are studied. In these failed cases, pathogenic organisms do not propagate in-vitro or may not proliferate to the extent necessary to study virulence or infectivity. In this project, growing human cell lines on collagen-coated microcarrier beads under conditions of physiological fluid shear in rotating wall vessel (RWV) bioreactors allows the cells to grow, differentiate and function as in a native, in-vivo 3-D environment. Alternatively, RWV bioreactors can be used to maintain and perform studies on primary tissue explants. This project applied RWV technology to study host responses of human lung epithelial models and mouse lung tissue explants to discover host molecular signatures that are up-or down-regulated in response to exposure to our model pathogen system.