# Distinguishing features of C. albicans pseudouridylation and their roles in pathogenesis

> **NIH NIH R15** · BALL STATE UNIVERSITY · 2021 · $433,183

## Abstract

Project Summary:
 The proposed research leverages recent technological breakthroughs to investigate aspects of
pseudouridylation and pseudouridine degradation that distinguish C. albicans from humans. Increased
resistance to the few treatment options available for C. albicans infection underscores the importance of
understanding how fungal pathogens differ from humans at the molecular level. The proposed research
addresses fundamental questions about C. albicans biology by investigating essential aspects of RNA
metabolism and has the potential to identify novel antifungal targets.
 The long-term objective of the proposed research is to understand how RNA modification and processing
differ between humans and pathogenic fungi. Pseudouridine is an RNA modification found in a wide variety of
RNA molecules in all kingdoms of life. Although pseudouridine is widespread, the amount and mechanism by
which pseudouridylation occurs varies tremendously between taxa. Preliminary data indicate C. albicans Pus7
is critical for biofilm formation and rRNA processing. The mechanisms by which Pus7 absence leads to these
phenotypes has not been investigated. Undergraduate and masters students will identify Pus7 substrates and
determine where it localizes in the cell. The data collected will begin to develop a model for Pus7’s role in vivo.
 When RNA is degraded, the pseudouridine C-C glycosidic bond is degraded by pseudouridine glycosidases
and kinases. While highly conserved in bacteria and most fungi these enzymes are not present in mammals or
members of the Saccharomyces fungal clade. Little is known about this family of enzymes and the experiments
proposed will be the first characterization of these enzymes in fungi. Undergraduate and masters students in the
Bernstein lab will knockout these enzymes and determine how this effects C. albicans phenotype. Students will
examine how pseudouridine glycosidase and kinase transcription is regulated. C-C glycosidic bond cleavage is
an enzymatic activity not found in mammalian cells, and as such could be an important therapeutic target.
 Answering these questions will demand students perform medically relevant experiments in an important
human fungal pathogen. Students in the Bernstein lab will gain experience in a wide variety of fundamental
molecular biology techniques including cutting-edge CRISPR genome-editing technology. Students will be
directly supervised by Dr. Bernstein and will participate in experimental design, data collection, interpretation,
and dissemination of results. Furthermore, portions of the experiments proposed will be incorporated into the
laboratory components of two courses taught by Dr. Bernstein, exposing an additional 32 students to significant
biomedical research every year. Undergraduate and masters students in the Bernstein laboratory and both
classes will be positioned to make discoveries that have a direct impact on our understanding of fungal
pathogenesis and human health. These experie...

## Key facts

- **NIH application ID:** 10291900
- **Project number:** 2R15AI130950-02A1
- **Recipient organization:** BALL STATE UNIVERSITY
- **Principal Investigator:** Douglas A. Bernstein
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $433,183
- **Award type:** 2
- **Project period:** 2017-02-06 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10291900

## Citation

> US National Institutes of Health, RePORTER application 10291900, Distinguishing features of C. albicans pseudouridylation and their roles in pathogenesis (2R15AI130950-02A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10291900. Licensed CC0.

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