February 21, 2023

Engineering a Living Diagnostic for Dynamically and Non-invasively Monitoring the Gut to Guide Nutritional Interventions

5th Call, TPdF

Short Summary

Precision nutrition is a highly interesting approach that aims to rationally design personalized nutritional interventions that helps individuals to keep a healthy life. However, currently this approach lacks reliable, non-invasive information about gut function. The host lab previously developed Record-seq, a technology that allows the generation of synthetic memory in bacterial cells. This project aims to safely engineer bacteria harboring Record-seq and to demonstrate that this newly generated diagnostic tool can be employed to record the presence of different metabolites and complex physio pathological conditions in vivo, what would clear the path to be deployed in humans in the near future for acquiring nutritional information while traversing the gastro intestinal system upon oral administration.

Goals

The objective of this project is to operationalize this tool in a safely engineered bacterium that would be able to traverse the gastrointestinal tract while recording rich and quantitative information describing gut composition and function along the length of the intestine.

Significance

This diagnostic tool would enable to establish mechanistic links as well as predict nutritional/therapeutic interventions to guide healthy and diseased individuals to their desired health outcomes – guiding healthy development, slowing down aging, preventing diabetes, expediting recovery from surgery or increasing the effectiveness of cancer treatments, and helping every individual know what lifestyle choices are best for them. The assessment of different nutritional parameters at the same time will avoid using tiring and time-consuming current nutrition tests, in which each nutritional parameter is measured individually. Furthermore, our system will record personal global nutritional profiles, information that will be stably stored on a long-term basis in the bacterial genome, allowing the recovery of specific nutritional information multiple times.

Background

Each of us is different, and still therapeutic diets are established without deeply considering our individual necessities or just based on trial and error approaches. This limitation is essentially due to the lack of robust, precise, faithful information about what is going on in the intestine of each person. My host lab recently created a radically new technology named Record-seq to fill this gap. Record-seq allowed the generation of synthetic transcriptional memory in engineered bacterial cells. Specifically, bacteria were programmed to record transcriptional events by CRISPR spacer acquisition-mediated capture of RNA proportionally to their abundance, information that can be retrieved from bacteria by computational analysis. Unlike current molecular recording technologies that only record specific stimuli, Record-seq provided a transcriptome-scale record of transcriptional events.