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Comparative transcriptomics of phylogenetically selected pathogenic treponemes cultivated in vitro under different conditions: First insight to the expression changes linked with genomic variants

Project description

Comparative transcriptomics of pathogenic treponemes cultivated in vitro

Treponema pallidum (TPA) is a bacterium that causes syphilis, which is considered a re-emerging disease with over 5.6 million cases worldwide. Surprisingly, very little is known about the basic biology and pathogenesis of TPA, largely because of the complicated in vitro propagation of the bacteria. A recently described in vitro culture model based on rabbit epithelial cells opens new possibilities for the study of the basic biology of this pathogen. The objective of the EU-funded ComTransTrep project is to apply the in vitro model combined with high-throughput genomic approaches to obtain data about the gene expression profiles of the TPA pathogen.

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.

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MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)

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Call for proposal

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(opens in new window) H2020-MSCA-IF-2019

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Coordinator

GENOME RESEARCH LIMITED LBG
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 212 933,76
Address
WELLCOME SANGER INSTITUTE WELLCOME GENOME CAMPUS HINXTON
CB10 1SA SAFFRON WALDEN
United Kingdom

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Region
East of England East Anglia Cambridgeshire CC
Activity type
Research Organisations
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 212 933,76
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