# Decoding Spatially Resolved Single Cell Metabolic Trajectory of Tonsil Tissues and Organoids

> **NIH NIH R21** · GEORGIA INSTITUTE OF TECHNOLOGY · 2023 · $196,750

## Abstract

Germinal centers (GCs) are the microstructural sites in secondary lymphoid organs that control B cell clonal
expansion to produce high-affinity antibodies for achieving humoral immunity. GC structures are impaired in
obstructive sleep apnea (OSA) patients, leading the deficiencies in immune responses in infected individuals.
The role of B cell development through GC reactions has been well established. B-cell immunometabolism is
crucial to meet the energy needs of rapid proliferation. OSA patients exhibited associations with metabolic
syndrome and vulnerability to flu. However, the coordination of metabolic trajectories in B cells of OSA+ and
OSA- patients is still not clearly understood. There is a critical need to decipher the B cell immunometabolism
at the single cell level in GCs for identifying the metabolic defects in the immune system of OSA patients
making them prone to life-threatening infections. Thus, this project will leverage the recently developed
spatially resolved metabolic profiling framework (3D-SMF) to map B cell subsets and their metabolism in the
tonsil tissues and organoids. Our long-term goal is to generate single cell metabolic insights of B cell
development in GCs of OSA+ and OSA- patients in response to influenza. The goal of this project is to define
spatially resolved B cell immunometabolism pixel-by-pixel in fixed human tissues and living tissues. We
hypothesize that metabolic trajectories and spatial distributions of B-cell subsets will be defective in OSA+
compared to OSA- tissues and influenza response in OSA- tonsil-derived organoids will be more competent
than OSA+ tonsil-derived organoids. The rationale for this hypothesis is based on the 3D-SMF data showing
the depletion and enrichment of fatty acids in GCs located in native tonsil tissues and the recent evidence on
OSA patients’ vulnerability to flu infections associated with metabolic syndrome. The central hypothesis will be
tested by pursuing two specific Aims. Aim 1 will provide an integral understanding of the lipid-associated
immunometabolism in B-cell subsets in human OSA+ and OSA- tonsil tissues (n=10 each) and engineered
tonsil organoids. Aim 2 will define how the metabolic trajectory modeling of B cell subtypes differs in tonsil
organoids exposed to influenza antigens in OSA+ and OSA- donors. To accomplish these Aims, 3D-SMF and
multiplexed cytokine gene expression profiling will be used to analyze B cell immunometabolism through a
pseudotime B cell development modeling and longitudinal metabolic trajectory comparisons of B cell subsets in
biomaterial-based tonsil organoids. This project builds an interdisciplinary team integrating experts from
spatial omics, biomaterials, pediatric OSA, and bioinformatics. The proposed application is innovative
because it uses cutting-edge technology to define spatial metabolomics and proteomics of tonsil organoids and
shifts from the traditional focus on T cell and B cell co-cultures, toward differences of B cell me...

## Key facts

- **NIH application ID:** 10751125
- **Project number:** 1R21AI173900-01A1
- **Recipient organization:** GEORGIA INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Ahmet F. Coskun
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $196,750
- **Award type:** 1
- **Project period:** 2023-08-10 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10751125

## Citation

> US National Institutes of Health, RePORTER application 10751125, Decoding Spatially Resolved Single Cell Metabolic Trajectory of Tonsil Tissues and Organoids (1R21AI173900-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10751125. Licensed CC0.

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