# Spatially Resolved Metagenomics to Explore Tumor-Microbiome Interactions in Human Colorectal Cancer

> **NIH NIH R33** · CORNELL UNIVERSITY · 2021 · $383,077

## Abstract

PROJECT SUMMARY
Microbes are increasingly recognized as a critical component of the tumor microenvironment of cancers that
arise at epithelial barrier surfaces, such as human colorectal cancer (CRC). Spatial interactions between
microbes and between microbes and host tissues, are fundamental to the mechanisms by which microbiota drive
carcinogenesis in CRC, yet these interactions remain poorly studied. This lack of knowledge is in large part due
to fundamental limitations of the tools available to study microbes and microbiomes. Microbiome studies primarily
rely on shotgun DNA sequencing, which destroys all information about the spatial context of microbes and their
functional interactions, or imaging methodologies that are limited to identifying a small number of organisms
using general species marker tags.
In this project, we will invent and apply spatially resolved metagenomics (SRM), a revolutionary
molecular analysis technology that enables to create micro-scale maps of the locations of thousands of
different bacterial species in dense microbial communities. SRM takes advantage of optical barcoding and
spectral imaging-based barcode decoding, enabling the identification of bacterial species by their unique 16S
ribosomal RNAs, and even quantification of host gene expression. SRM is a flexible and inexpensive technology
that increases the number of unique microbial species that can be identified over existing methods by at least
two orders of magnitude and is well supported by pilot data. We will investigate three aims. First, we will refine
a host of innovative technologies that together lay the foundation for SRM, including but not limited to software
for the automated design of hybridization probes, spectral imaging procedures and software for the automated
annotation of images. Second, we will design and construct a custom broad-wavelength confocal microscope,
that will improve the multiplexity, and speed of SRM by an additional order of magnitude, which in turn will
improve the range of possible applications of SRM. Third, we will perform rigorous validation of SRM in
experiments that address highly timely questions in human CRC. The functional roles of cancer-promoting
microbes in CRC, the role for biofilm formation as a consequential, early event in CRC development, and the
presence of a persistent microbiome in CRC tumors, are all very recent landmark discoveries, that we will be
able to study with unprecedented spatial and phylogenetic resolution by taking advantage of the features SRM.
SRM enables to survey not only who is there, but also who is next to who and who is next to what, and therefore
provide a powerful, novel means to study the functional role of microbiota in the initiation and progression of
CRC, a disease that accounts for more than 50,000 deaths annually in the US.

## Key facts

- **NIH application ID:** 10248372
- **Project number:** 5R33CA235302-03
- **Recipient organization:** CORNELL UNIVERSITY
- **Principal Investigator:** Ilana Lauren Brito
- **Activity code:** R33 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $383,077
- **Award type:** 5
- **Project period:** 2019-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10248372

## Citation

> US National Institutes of Health, RePORTER application 10248372, Spatially Resolved Metagenomics to Explore Tumor-Microbiome Interactions in Human Colorectal Cancer (5R33CA235302-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10248372. Licensed CC0.

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