Nasal Microbiome Engineering for Enhanced Olfaction
Abstract
Nasal Microbiome Engineering for Enhanced OlfactionOlfaction allows the sensitive detection of numerous threats by people and canines. This project will determine the feasibility of extending mammalian olfaction to detect molecules that would not otherwise be perceived. To preserve the advantages of olfaction as an always-on detection modality that requires no external equipment, we seek to engineer microbes that can persist, for a time, within the nasal microbiome. Specifically, we will engineer a strain that contains analyte-triggered odor-generation genes as well as biocontainment genes. Ultimately, these engineered microbes will have a defined and tunable lifetime in the nasal microbiome. The resulting strains could provide expanded olfactory capabilities to enhance the capabilities of warfighters or canines. To validate the central concept, this project will demonstrate that a model small molecule analyte found in tea, theophylline, can trigger the generation of methyl salicylate (wintergreen) odor. Objective 1 will accomplish this task by integrating established genetic components such as the enzyme salicylic acid methyltransferase (SAMT) within a microbe, Staphylococcus carnosus , that is generally recognized as safe. A single molecule of analyte will trigger translation of multiple SAMT enzymes via a riboswitch, and each enzyme can catalyze the synthesis of many odorant molecules. This approach has the potential for significant amplification of the olfactory response.We will use animal trials and microbiome analysis to quantify the lifetime of the engineered microbe in the nasal cavities of rats. We will further verify that we can use our genetic kill switch to eliminate the engineered microbe at will. We will train the rats to indicate wintergreen perception, and demonstrate that they can perceive wintergreen odor produced within the nasal cavities (constitutive or analyte triggered). To improve response speed, Objective 2 will augment the riboswitch with engineered SAMT enzyme variants that are activated by analyte binding. Enzyme-level switches that provide rapid conditional odor production could open up entirely new dynamic sensing applications by reducing latency.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Aug 15, 2019
- Source ID
- N000141912437
Entities
People
- Christopher D Snow
Organizations
- Colorado State University
- Office of Naval Research
- United States Navy