# Molecular profiling of global tissue dynamics at sub cellular resolution

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2024 · $332,892

## Abstract

The relationship between structure and function is central to understanding how many biological and
chemical processes operate, across length scales from small molecule chemicals to gross anatomy. Through
an explosion in new technologies, including single-cell RNA sequencing (scRNAseq) and multiplexed tissue
imaging (MTI), tissues can now be visualized with incredible molecular and cellular detail. However, such rich
atlases of tissue structure are typically static snapshots from a ﬁxed sample, and lack important information
about how the tissue actually functions — how cells, ﬂuids, and biomolecules dynamically interact to govern
multicellular behaviors. Our project aims to overcome this limitation by building an integrated computational
and experimental platform for quantitatively linking functional dynamics within tissue to a high-resolution
spatial map of its molecular and cellular composition. As a result, the project aims to produce Molecular
proﬁling of Tissue Dynamics (MOTID) as a generalizable method that links structure with function in
multicellular communities, designed to be applicable across diverse models, tissue-types, and dynamic
readouts. In this project, we aim for MOTID to be capable of simultaneously monitoring the dynamic
morphology and migration of a substantial fraction all cells within a tissue region, combined with the ﬂuid-
phase movement of particular molecules moving from microvascular circulation through interstitium. Highly
multiplexed imaging of the same tissue, guided by interactive statistical mining of complementary genomic
data, will reveal immunologically-deﬁned cell-type identities that correspond to the observed dynamic
behavior. Thus, MOTID will provide a functional atlas that correlates cellular and ﬂuid dynamics with molecular
markers of cell state. As proof of principle applications upon which to validate the technology, we will
examine dynamic behaviors in a mouse model of ischemia/reperfusion injury in the beating heart, and a
genetically engineered model of malignant melanoma. To accomplish the successful development of MOTID,
this project builds upon our team's expertise and extensive preliminary data in intravital microscopy,
segmentation of single-cell dynamics within live tissues, interpretation of highly multiplexed data, and building
integrated experimental/computational platforms for systems-level analysis.

## Key facts

- **NIH application ID:** 10907018
- **Project number:** 5R01GM138790-03
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Miles A Miller
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $332,892
- **Award type:** 5
- **Project period:** 2022-09-20 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10907018

## Citation

> US National Institutes of Health, RePORTER application 10907018, Molecular profiling of global tissue dynamics at sub cellular resolution (5R01GM138790-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10907018. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*
