# Microsystems to Decipher Leukocyte Decision-Making

> **NIH NIH R35** · UNIVERSITY OF TEXAS DALLAS · 2022 · $375,882

## Abstract

Emerging studies suggest that innate immune cells, such neutrophils, can adopt multiple
activation/differentiation states, either conducive or detrimental to host defense and inflammation resolution.
The conceptual existence of diverse activation states of innate leukocytes is also evident in circulating
leukocytes from healthy individuals and patients with system inflammatory syndromes such as sepsis.
However, quantification and understanding of single-cell phenotypes in a spectrum of differentiation states is
lacking. This bottle-neck explains the complete lack of cure for sepsis, despite decades of extensive basic and
translational studies. The overarching focus of the research program in my laboratory is to define and
quantify principal factors that underlie the decision-making processes of immune cell migration,
differentiation and activation in response to challenges. The research funded by this award will
combine technologies, experimental methods, and modeling approaches to investigate leukocyte
decision-making in the context of activation state and sepsis. In the past 5 years, we have engineered
microfluidic platforms to quantify neutrophil migratory and anti-microbial decision-making. Building off of our
current work with neutrophils and microfluidic platforms, over the next five years we propose to: 1) Develop,
improve and implement state-of-the-art multi-sensing platforms to analyze septic patient leukocyte migratory
and antimicrobial phenotypes in precisely defined microenvironments. Mathematical models will be created
based on known molecular pathways and will be validated by the molecular signatures from septic patients and
healthy donors; 2) Quantify leukocyte migratory and anti-microbial functions in vivo using novel implantable
hydrogels combined with intra-vital imaging techniques in a mouse sepsis model. By defining the fundamental
processes, including differentiation state and microenvironment, that determine a leukocyte’s phenotype, we
can better predict, diagnose, and eventually design effective treatments for sepsis. These fundamental
processes involve general biology principles at cellular and molecular levels applicable to diverse eukaryotic
cells, lending broader significance to our proposed investigation. The work proposed is highly innovative
because it integrates methods from different scientific disciplines to solve the “big problem” of sepsis. Novel
microfluidic platforms will be engineered to measure single-cell phenotypes in precisely defined conditions and
directly connect these phenotypes to the molecular signature of the cell. Our vision is to integrate these
quantitative single cell measurements with computational modeling and analysis to create intuitive descriptions
of complex leukocyte decision-making processes. Finally, these devices have clear translational potential and
may be used in the future in a hospital setting to assist with diagnosing or monitoring treatment of sepsis.

## Key facts

- **NIH application ID:** 10436263
- **Project number:** 5R35GM133610-05
- **Recipient organization:** UNIVERSITY OF TEXAS DALLAS
- **Principal Investigator:** Caroline N. Jones
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $375,882
- **Award type:** 5
- **Project period:** 2019-09-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10436263

## Citation

> US National Institutes of Health, RePORTER application 10436263, Microsystems to Decipher Leukocyte Decision-Making (5R35GM133610-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10436263. Licensed CC0.

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