Effective responses to biological threats are inextricably related to effective responses to emergingpathogens [Countering Bioterrorism: the Role of Science and Technology, NAS report 2002]. The etiologiesof many human diseases are unknown, but may be infectious. New viruses can enter the human populationwith devastating effect, and the intentional release of new or engineered agents is a danger. When newtechnologies are applied to the problem of detecting emerging agents or agents associated with diseases ofunknown etiology, new pathogens have been discovered, resulting in significant advances in human healthand in the development of new and useful diagnostics. These diagnostics, particularly if they are relativelyunbiased in what they can detect can play a role in detecting emerging pathogens or biological threats. Thus,discovery of new agents walks hand in hand with effective responses to bioterrorism. In light of theseconsiderations, we proposed to develop the infrastructure and expertise to identify new agents of humandisease in a Project designed to: (i) bring the most advanced technologies to the problem of discovering newpathogens, (ii) apply these technologies and approaches in a serious and high throughput way to clinicalsamples carefully selected to contain unknown or emerging pathogens, and (iii) through this effort bring newdiagnostic and discovery tools on line for identifying epidemic agents in clinical specimens. Potentialdeliverables from this Project include new pathogens associated with human disease, the infrastructure andtrained professionals required to identify pathogens during an outbreak, and diagnostic tests andtechnologies. To date, we have delivered the discovery of one new human virus, and have developed theneeded sample pipeline and technologies. We propose to continue this project via three Aims.
Aim 2 d is anew Aim based on development and validation of new technologies.
Aim 1) Identify clinical materials appropriate for pathogen discovery experiments.
Aim 2) Identify novel pathogens by applying:
Aim 2 a) Pan-viral microarray technology.
Aim 2 b) Representational Difference Analysis (RDA).
Aim 2 c) Passage of agents in severely immunocompromised mice.
Aim 2 d) Mass sequencing and informatic and an informtics pipeline.
Aim 3) Determine if novel pathogens are present in clinical samples.
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