Rapid Detection of Cellular Response to Biological Agents
Abstract
Our program objective is to develop simple and rapid methods for detecting at a cellular level, individual responses to environmental stresses elaborated by exposure to infectious agents such as bacteria and viruses. Our methods are based on transcript profiling and post-translational modification of proteins involved in signal transduction. Our hypothesis is that human cells respond to infectious insults to a genetically predetermined extent by stimulating the expression of sets of genes and activating signaling pathways that provide a specific signature for a given agent. We propose that this response will determine the outcome of the infection. We will test this hypothesis by developing custom cDNA and protein arrays designed to detect cellular responses to infectious agents. These will be tested using RNA and protein isolated from tissues sources most likely to be exposed. Our long term goal is to develop rapid quantitative detection devices to measure exposure and response to biological warfare, bioterrorism or emerging agents enabling appropriate triaging and medical intervention to save lives and to avoid unnecessary treatments. We have made significant progress towards this goal during the funded period of 1 Oct 2001 - 28 Feb 2005. We have used our custom cDNA microarrys to characterize the responses of mouse and human cells, in vitro and in vivo, to a variety of pathogens and shown that transcriptional profiles can indeed serve to differentiate between types of infections. We have made progress in the development of single chain antibodies for use in protein arrays to detect activation of signaling pathways impacted by biological agents. Moreover, the course of these studies, we have made a number of discoveries regarding the involvement of specific pathogen and host factors in the mechanisms and regulation of these signaling pathways.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 01, 2005
- Accession Number
- ADA471370
Entities
People
- Bryan R. Williams