# The temporal dynamics of translation efficiency during an innate immune response

> **NIH NIH R21** · VANDERBILT UNIVERSITY · 2022 · $290,879

## Abstract

PROJECT SUMMARY/ABSTRACT
 The induction of an innate immune response to bacterial infection is a complex process that requires the
rapid and efficient conversion of the microbial detection event into a set of functional defense responses.
Thousands of genes can become differentially regulated at the transcriptional level in the early stages of this
process, setting off the suite of physiological shifts that prepare the host to respond to the infection. However,
there is currently a large gap in our knowledge concerning the dynamics of the progression of these messages
into functional proteins during an innate immune response. Recent evidence suggests that regulatory
components responsible for guiding and preparing transcripts to attach to ribosomes for translation can
introduce selective bias into the translation process. Thus, translation initiation represents a potential source of
substantial immunological variation from individual to individual. In particular, across a large swath of taxa
from insects to mammals, previous exposure to microbes can impart a form of memory to future innate immune
responses, resulting in heightened resistance and survival outcomes upon subsequent infection. Our recent data
from primed Tribolium castaneum flour beetles suggests a role for shifts in translation initiation dynamics in the
priming phenotype, resembling translation initiation shifts recently observed in mammalian macrophages
trained against microbial elicitors. These parallel innate immune memory phenomena challenge our canonical
understanding of the functional and evolutionary divide between innate and adaptive immune systems, and
demand further investigation into the role of translation initiation biases in generating defense phenotypes.
 The first aim of this proposal is to investigate the fidelity of translation initiation to transcriptional shifts
observed during the innate immune response induced by bacterial infection over time. We will determine the
role of translation initiation in facilitating biases in translation efficiency using ribosomal profiling (Ribo-Seq)
in the powerful model organism T. castaneum infected with Bacillus thuringiensis, taking advantage of the tight
evolutionary conservation of translation initiation machinery from yeast to humans. The second aim of this
project is to manipulate the expression of translation initiation factors using RNAi-mediated knockdown to
investigate the role of translation efficiency in generating variation in innate defense and memory phenotypes.
 Our long-term goal is to understand the underlying mechanisms of variation in the dynamics of innate
immune responses so that more effective approaches can be designed for the treatment of sepsis and immuno-
pathological conditions. By investigating the dynamics of translation initiation during the early phase of
bacterial infection and its contribution to variation in innate immune phenotypes, we will be developing a
promising frontier for the treatment...

## Key facts

- **NIH application ID:** 10507565
- **Project number:** 1R21AI170977-01
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** Ann Thomas Tate
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $290,879
- **Award type:** 1
- **Project period:** 2022-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10507565

## Citation

> US National Institutes of Health, RePORTER application 10507565, The temporal dynamics of translation efficiency during an innate immune response (1R21AI170977-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10507565. Licensed CC0.

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