# Molecular mapping of microbial communities at the host-pathogen interface by multi-modal 3-dimensional imaging mass spectrometry

> **NIH NIH R01** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2022 · $595,077

## Abstract

PROJECT SUMMARY
 Cellular interactions with the environment form the basis of health and disease for all organisms. Exposure
to nutrients, toxins, and neighboring cells trigger coordinated molecular responses that impact cell function and
metabolism in a beneficial, adaptive, or detrimental manner. Although the benefits of multicellularity for the
formation of complex tissue structures or the function of entire organ systems has been long appreciated, it has
only recently been understood that microbial inhabitants of vertebrates also have a tremendous impact on host
cell function and dysfunction. Despite this, an understanding of these interactions has not moved beyond simple
associations, and there are virtually no molecular technologies available that adequately define how a complex
microbial ecosystem impacts host cell function, or how the host response to microbial colonization affects the
bacterial community. This gap in knowledge is striking when one considers the broad and significant impact that
microbes have on human health. In this application, we propose to expressly fill this knowledge gap through
development of a novel multimodal imaging pipeline that will provide 3-dimensional information on the molecular
heterogeneity of microbial communities and the immune response at the host-pathogen interface.
 This proposal combines our expertise in immunology, infection biology, mass spectrometry, small animal
imaging, machine learning, and computer vision to develop an integrated multimodal visualization method for
studying infectious disease. Our unique approach will computationally combine ultra-high speed (~50px/s)
MALDI-TOF images, ultra-high mass resolution (>200,000 resolving power) MALDI FTICR IMS, metal imaging
by LA-ICP-IMS, high-spatial resolution optical microscopy, and MR imaging using data-driven image fusion. This
strategy will enable 3-D molecular images to be generated for thousands of elements, metabolites, lipids, and
proteins with an unprecedented combination of chemical specificity and spatial fidelity more than 50x faster than
is currently possible. We will use this next-generation imaging capability to (i) define the heterogeneous microbial
subpopulations throughout the 3-D volume of a S. aureus community, (ii) uncover the host molecules that form
the abscess and accumulate to restrict microbial growth in murine models, and (iii) elucidate molecular markers
that differentiate in vivo biofilms at the host-pathogen interface, between abscesses at various stages of
progression, and under distinct degrees of nutrient stress. These studies will uncover new targets for therapeutic
intervention and the techniques developed as a result of this proposal will be broadly applicable to all
physiologically relevant processes, profoundly impacting biomedical research.

## Key facts

- **NIH application ID:** 10465090
- **Project number:** 5R01AI138581-05
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Eric P Skaar
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $595,077
- **Award type:** 5
- **Project period:** 2018-09-19 → 2024-07-01

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10465090

## Citation

> US National Institutes of Health, RePORTER application 10465090, Molecular mapping of microbial communities at the host-pathogen interface by multi-modal 3-dimensional imaging mass spectrometry (5R01AI138581-05). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10465090. Licensed CC0.

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