# Mechanisms of host protection during infection via the mitochondrial unfolded protein response

> **NIH NIH R35** · UNIVERSITY OF TEXAS ARLINGTON · 2021 · $372,177

## Abstract

Project Summary
The rise of antibiotic resistant pathogens in the clinic is undeniably a recognized medical concern since
it is the cause of enormous human and economic loss worldwide. Of further alarm is the lack of new
therapeutics to combat these harmful and potentially deadly infections. Accordingly, it is critical that we
generate novel approaches to address this growing problem. The development of reagents that
enhance host immunity may be an effective alternative strategy to promote host resistance to infection
by reducing pathogen numbers. In addition, identifying mechanisms that can support host tolerance to
withstand the damage inflicted by harmful microbes and the inflammatory response is equally as vital.
Mitochondria have multiple essential cellular functions including a recognized role in mediating the
immune response. The mitochondrial unfolded protein response (UPRmt), a stress-activated pathway
that recovers mitochondrial function, also participates in host defense against infection through the
regulation of innate immunity. Further investigation into the regulation and therapeutic potential of the
UPRmt is therefore warranted considering its dual roles in preserving mitochondrial homeostasis and
inducing anti-microbial defense. The current proposal will explore the UPRmt in the context of pathogen
infection to uncover novel mechanisms of its regulation by both the host and the infectious agent. Here
we will employ a combined approach using the powerful genetic model organism Caenorhabditis
elegans and the opportunistic bacterial pathogen Pseudomonas aeruginosa, an established system in
the study of host-microbe interactions. Moreover, we will build on our current understanding by
evaluating the potential role of the mammalian UPRmt in promoting host survival during infection.
Collectively, the outcomes from our proposed research plan are expected to yield novel insights of the
UPRmt during infection that potentially may be used to enhance host protection during infection.

## Key facts

- **NIH application ID:** 10220071
- **Project number:** 5R35GM128885-04
- **Recipient organization:** UNIVERSITY OF TEXAS ARLINGTON
- **Principal Investigator:** Mark Watson Pellegrino
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $372,177
- **Award type:** 5
- **Project period:** 2018-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10220071

## Citation

> US National Institutes of Health, RePORTER application 10220071, Mechanisms of host protection during infection via the mitochondrial unfolded protein response (5R35GM128885-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10220071. Licensed CC0.

---

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