Next-Generation Massively Parallel Cellular Biosurveillance and Recording Devices
Abstract
.The overarching goal of the proposed research is to develop foundational synthetic biology technologies that enable the accurate, reproducible, and parallel recording of environmental events in cells at both the spatial and temporal scale. We will devise a molecular reading and recording strategy that utilizes the bacterial CRISPR immunity system whereby specific spacer sequencescan be incorporated into the CRISPR array to denote the recording event upon triggering by an environmental stimulus. We will devise both molecular and genomic strategies to read and write the CRISPR array at high precision and accuracy, and with reduced cost far beyond current capabilities. Furthermore, we will test these strategies in bacterial cells both in laboratoryconditions as well as in the murine gastrointestinal tract to replicate recording of a complex environmental setting. Recording of environmental cues will involve detection of host-derived markers (e.g. inflammation), pathogenic marks (e.g. C. diff infection), and toxin exposure (e.g. heavy metals). These actuated signals will be generated in sentinel bacterial cells that will bedeployed in the murine gastrointestinal tract over the course of weeks and the spatial and temporalrecorded information will be extract from these animals both from fecal matter as well as from dissection of the GI tract for further validation. Together, this work is poised to transform rapid and large-scale simultaneous molecular recording of cellular events over large space and time scales to enhance future naval capabilities to monitor and augment complex microbiomes.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- May 05, 2017
- Source ID
- N000141712353
Entities
People
- Harris H. Wang
Organizations
- Office of Naval Research
- Trustees of Columbia University in the City of New York
- United States Navy