# Stress Responsive Reprogramming of Translating mRNA Pools in C. neoformans

> **NIH NIH R01** · STATE UNIVERSITY OF NEW YORK AT BUFFALO · 2021 · $457,683

## Abstract

Abstract:
 Cryptococcus neoformans is a major comorbidity of HIV infection and transplantation with high mortality
rates due to the toxicity and limited availability and efficacy of existing antifungal agents. As an environmental
saprophyte, cryptococcal pathogenesis requires adaptation to the environment of the human host. Our work
has led us to the scientific premise that stress adaptation in C. neoformans requires two sequential post-
transcriptional events. First, the accelerated degradation mRNAs encoding metabolically expensive processes
such as the translational machinery, and second, the translation of stress response mRNAs via cap-
independent translation mechanisms on recycled ribosomes. This premise implicates the ribosome as a sensor
of cellular stress through translation quality control mechanisms. The aims in this proposal will investigate co-
translational quality control as a trigger for accelerated mRNA degradation in response to temperature sturess
(Aim1) and will investigate cap-independent translation mechanisms (Aims 2) in stress adaptation. Aim 2 will
focus on two CNBP orthologues expressed in C. neoformans that we hypothesize to regulate translation via
internal ribosome entry sites (IRES) in response to temperature and oxidative stress. Finally, we will assess
the contributing role of ribosome-associated quality control in starvation stress responsive translation and
define the contributions of each quality control pathway in the response of C. neoformans to compound
stressors (Aim 3). These studies will be the first investigation of translation in C. neoformans, and include the
first application of ribosome profiling in this pathogen. Translation is known to be pharmacologically targetable
but conservation in eukaryotes is thought to be a hindrance. Only through molecular investigation of translation
regulation can fungal-specific aspects of the process be identified for future investigation as drug targets.

## Key facts

- **NIH application ID:** 10144372
- **Project number:** 5R01AI131977-05
- **Recipient organization:** STATE UNIVERSITY OF NEW YORK AT BUFFALO
- **Principal Investigator:** John C Panepinto
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $457,683
- **Award type:** 5
- **Project period:** 2017-05-10 → 2023-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10144372

## Citation

> US National Institutes of Health, RePORTER application 10144372, Stress Responsive Reprogramming of Translating mRNA Pools in C. neoformans (5R01AI131977-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10144372. Licensed CC0.

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