# Core B. Genomics and Bioinformatics Core

> **NIH NIH U19** · UNIVERSITY OF PENNSYLVANIA · 2024 · $172,353

## Abstract

SUMMARY- CORE B (GENOMICS CORE)
Core B (Genomics Core) will provide key support to the mVACS team in Clostridioides difficile genome sequence
analysis, antigen design, microbiome sequence analysis, routine statistical analysis, and high content data
management. Core B will use advanced genomics-based methods to quantify C. difficile genome composition
and genetic variation, and associate these with outcomes. Core B will support analysis of protein structure to
allow expression of well-folded domains as mRNAs. Core B will characterize DNA inversion systems and other
mechanisms of DNA modification and alterations in gene activity that may impact vaccine efficacy. Core B will
also carry out transcriptional profiling on C. difficile isolated from the intestine of vaccinated and immunodeficient
mice, to assess how C. difficile responds in vivo to effective and ineffective immune responses. The Aims of
Core B are: (1) C. difficile genomics to identify optimal targets for modified mRNA vaccines. Long read and short
read data will be merged to generate complete assemblies, as in our previous work. Gene content will be
enumerated and compared with clinical outcomes. (2) To assess variation in sequence and abundance of C.
difficile vaccine targets. C. difficile isolates are known to encode considerable variation in their surface proteins.
In addition, DNA inversion systems encode on-off switches affecting surface proteins and transcription factors,
resulting in extensive population heterogeneity. This Aim will thus carry out deep assessment of proteins relevant
as modified mRNA vaccine targets, and guide antigen design. (3) Transcriptional profiling and microbiome
sequencing for mechanistic investigation. Projects 1-3 and the Clinical Core will generate murine and human
fecal samples associated with successful or unsuccessful responses to C. difficile infection; Core B will quantify
microbiome composition and metatranscriptomic analysis of C. difficile positive samples by RNA-seq. This core
will oversee sequence acquisition and analysis is support of these studies. (4) Data management and archiving.
Core C will work with Core A for standard statistical analysis and will archive and manage the diverse data types
generated by the U19 team.

## Key facts

- **NIH application ID:** 10792888
- **Project number:** 5U19AI174998-02
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Frederic D Bushman
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $172,353
- **Award type:** 5
- **Project period:** 2023-03-01 → 2028-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10792888

## Citation

> US National Institutes of Health, RePORTER application 10792888, Core B. Genomics and Bioinformatics Core (5U19AI174998-02). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10792888. Licensed CC0.

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