CORDIS - EU research results
CORDIS

Translational control in infection biology: riboproteogenomics of bacterial pathogens

Project description

Proteomic insight during bacterial infection

Understanding host–pathogen interactions is central for tackling infections. Moreover, understanding the molecular changes from a pathogen’s perspective that underpin a successful infection is required for the design of new therapies. The EU-funded PROPHECY project focuses on how pathogens change their proteins during infection. The work will employ Salmonella typhimurium as a model pathogenic organism to study transcription and translation during infection using cutting-edge techniques. Emphasis will also be given to the underlying regulatory processes. PROPHECY is expected to identify new virulence factors that will pave the way towards the development of novel diagnostics and therapeutics.

Objective

My recent findings revealed translation of numerous previously unidentified (small) open reading frames and expression of alternative N-terminal proteoforms when studying bacterial translation. This proposal aims at unraveling the repertoire of bacterial pathogen proteoforms employed to establish a successful infection in a mammalian host cell.

While deep sequencing has enabled the study of gene expression at the transcript level in both pathogen and host simultaneously, the depth of sequencing has so far proven to be unsatisfactory. Moreover, the study of bacterial proteome changes upon infection remains highly unexplored because of the higher proteome complexity of the host cell compared to the pathogen. These challenges clearly stresses the need for novel strategies based on complementary proteogenomics approaches enabling translation control studies in bacterial pathogens in a host context .

I here propose the development and application of a complementary cutting-edge proteogenomic toolset which will enable for the first time targeted systematic genome- and proteome-wide surveys of bacterial transcriptional and translational activity during actual host cell infection. This ambitious endeavor will lead to:

I) Establishment of dual Ribo-seq that allows the selective isolation of host or bacterial ribosomes, enabling to study the bacterial translatome in a host cell context.

II) Development of tailored proteomics strategies permitting the selective isolation of (nascent) bacterial protein N-termini and enrichment of bacterial small ORF-encoded polypeptides (SEPs). Further, proteome-wide subcellular localization and protein stability studies will provide a dynamic view on bacterial protein expression.

II) Bacterial proteoform interaction maps by the development of an innovative proxeome strategy.

The identification of new pathogen virulence factors will contribute to the development of therapeutics and diagnostics for multiple models of infectious diseases.

Host institution

UNIVERSITEIT GENT
Net EU contribution
€ 1 498 625,00
Address
SINT PIETERSNIEUWSTRAAT 25
9000 Gent
Belgium

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Region
Vlaams Gewest Prov. Oost-Vlaanderen Arr. Gent
Activity type
Higher or Secondary Education Establishments
Links
Total cost
€ 1 498 625,00

Beneficiaries (1)