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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

Descrizione del progetto

Trascrittomica comparativa di treponemi patogeni coltivati in vitro

Il treponema pallidum (TPA) è il batterio responsabile della sifilide, una malattia considerata riemergente con oltre 5,6 milioni di casi in tutto il mondo. Stranamente si sa ben poco della biologia di base e della patogenesi del batterio, in gran parte a causa della sua complicata propagazione in vitro. Un modello di coltura in vitro di recente descrizione basato sulle cellule epiteliali dei conigli apre nuove possibilità allo studio della biologia di base di questo patogeno. L’obiettivo del progetto ComTransTrep, finanziato dall’UE, è di applicare il modello in vitro insieme ad approcci genomici ad alto rendimento, al fine di ottenere dati sui profili di espressione genica del treponema pallidum.

Obiettivo

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.

Campo scientifico (EuroSciVoc)

Parole chiave

Programma(i)

Argomento(i)

Meccanismo di finanziamento

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

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Invito a presentare proposte

(si apre in una nuova finestra) H2020-MSCA-IF-2019

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Coordinatore

GENOME RESEARCH LIMITED LBG
Contributo netto dell'UE
€ 212 933,76
Indirizzo
WELLCOME SANGER INSTITUTE WELLCOME GENOME CAMPUS HINXTON
CB10 1SA SAFFRON WALDEN
Regno Unito
Regione
East of England East Anglia Cambridgeshire CC
Tipo di attività
Research Organisations
Collegamenti
Costo totale
€ 212 933,76