ComTransTrep · Comparative transcriptomics of phylogenetically selected pathogenic treponemes cultivated in vitro under different conditions: First insight to the expression changes linked with genomic variants
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2021-02-01 → 2023-06-04
- EU contribution
- €212,934
- Participants
- 1
- Scheme
- MSCA-IF
Lines connect the coordinator with its partners.
Results in brief
Comparative transcriptomics of phylogenetically selected pathogenic treponemes cultivated in vitro under different conditions: First insight to the expression changes linked with genomic variants
Despite over a century of scientific research on Treponema pallidum subsp. pallidum (TPA), the infectious agent of syphilis, our understanding of its biology is very limited. This is mainly because, in general, pathogenic treponemes are considered uncultivable bacteria, and the very small number of treponemal cells that can be obtained from clinical samples are insufficient for most scientific experiments. In 2018, a researcher reported the first successful long-term in vitro co-cultivation of TPA with rabbit skin epithelial cells (Sf1Ep) in TPCM-2 medium. Despite being technically challenging, requiring specially trained personnel, and being limited to strains previously propagated in experimental animals, this culture system holds the potential to enhance our understanding of treponemal biology. The main aims of the ComTransTrep project were to take advantage of this co-culture system, revise the transcriptional landscape of TPA, and provide a fundamental understanding of how different TPA strains vary at the transcriptomic level. Furthermore, I intended to compare these data with the genomes, thereby creating an opportunity to link genomic data to functional transcriptomics and, ultimately, to phenotype.
Data: CORDIS, © European Union
Project objective
Syphilis, caused by the bacterium Treponema pallidum subsp. pallidum (TPA) is considered a re-emerging disease with over 5.6 million cases worldwide. Despite causing severe life-threatening infections, very little is known about the basic biology and pathogenesis of TPA, largely as the result of the inability to routinely propagate it in vitro. The recently described in vitro culture model (containing rabbit epithelial cells) has opened new avenues for the study of the basic biology of this pathogen. The ultimate goal of my research proposal is to take advantage of the in vitro model and link its use to high throughput genomic approaches to provide unique insights into the gene expression profiles of this pathogen. This has been transformative for other bacteria, enhancing our knowledge of genetic regulation: essential genes vs differentially expressed genes and intra- and inter-strain differences in response to different growth conditions. This has not been possible until now for TPA. Here, I will perform dual RNA-seq of multiple strains grown in vitro under different conditions. This research proposal has three aims. First, to describe global gene expression patterns of phylogenetically selected TPA strains. Second, to describe genome-wide interaction-linked transcriptional alterations of the infected host cells. And lastly, to correlate the whole transcriptome data with genomic and allelic diversity we see in circulating clinical TPA populations. This project will generate novel fundamental data which can lead to identification of functional pathways and prediction of the function for hypothetical genes, give light to the patterns of selection we see in genomic data and a better understanding of the key growth dependencies that could inform future axenic cultivation of TPA and combined a better understanding of basic biology introduce a more mechanistic understanding to surveillance and genomic epidemiology.
Original text from CORDIS.
Participants
- GENOME RESEARCH LIMITED LBG · SAFFRON WALDENCoordinatorUnited Kingdom
Links
Data: CORDIS, © European Union