Noise in gene expression as a determinant of virulence of the human pathogen Streptococcus pneumoniae

Cel

Not all cells in bacterial populations exhibit exactly the same phenotype, even though they grow in the same environment and are genetically identical. One of the main driving forces of phenotypic variation is stochasticity, or noise, in gene expression. Possible molecular origins contributing to noise in protein synthesis are stochastic fluctuations in the biochemical reactions of gene expression itself, namely transcription and translation.

The driving hypothesis of this application is that the human pathogen Streptococcus pneumoniae utilizes noisy gene expression to successfully colonize and invade its host. To test this supposition, the total amount of noise in key regulatory networks for virulence factor production will be quantified. Using natural and synthetic bistable switches as highly sensitive probes for noise, in combination with state-of-the-art single-cell imaging, microfluidics and direct transcriptome sequencing, the molecular mechanisms underlying noise generation in S. pneumoniae will be determined. By constructing strains with altered levels of phenotypic variation, the importance of noisy gene expression in S. pneumoniae pathogenesis will be tested.

S. pneumoniae is a leading cause of bacterial pneumoniae, meningitis, and sepsis worldwide. The molecular mechanisms that cause switching of S. pneumoniae to its virulent states are barely understood, although it becomes increasingly clear that noise-driven phenotypic variation plays an important role in pneumococcal pathogenesis. Therefore, understanding the molecular origins of phenotypic variation in S. pneumoniae might not only provide novel fundamental insights in gene expression, but also result in the identification of new anti-pneumococcal targets.

Dziedzina nauki

System finansowania

ERC-SG - ERC Starting Grant

Instytucja przyjmująca

RIJKSUNIVERSITEIT GRONINGEN

Wkład UE

€ 1 498 846,00

Adres

Broerstraat 5
9712CP Groningen
Niderlandy

Region

Noord-Nederland Groningen Overig Groningen

Rodzaj działalności

Higher or Secondary Education Establishments

Kontakt administracyjny

H.D. Veldhuis (Dr.)

Kierownik naukowy

Jan-Willem Veening (Dr.)

Linki

Kontakt z organizacją Strona internetowa

Koszt całkowity

Brak danych

Beneficjenci (1)