Self-funded project: Targeting bacterial pathogenicity: the importance of genome segregation

Application accepted for either MSc by Research or PhD.

Enteropathogenic Escherichia coli is a serious threat to human health worldwide, with more
devastating consequences in countries of the developing world. It causes diarrheal diseases by
colonizing the small intestine through attachment of bacteria to epithelial cells. The localized
adherence of bacteria clusters causes the formation of pedestal-like structures in the epithelial cells
and determines the loss of nearby microvilli. In the enteropathogenic E. coli strain B171, the ability to
adhere to epithelial cells is mediated by adherence virulence factors encoded by the plasmid pB171.
A study has demonstrated that a plasmid-cured enteropathogenic E. coli strain was significantly less
pathogenic than the parental strain. Therefore, investigating the stability and inheritance mechanisms
of this plasmid will pave the way to devising possible strategies to target the plasmid segregation
machinery and thus cure the plasmid from pathogenic strains.
 
The mobile genetic element pB171 is a 70 kb low copy number plasmid. Large, low copy number
plasmids have evolved sophisticated strategies to ensure their faithful distribution at cell division.
They harbour their own survival system, a segregation cassette, which ensures an accurate and
equitable segregation of the plasmids from one generation to the next at cell division. When this
system malfunctions, the plasmid is not stably inherited and is ultimately lost.
The segregation cassette of pB171 consists of two genes, one that encodes an ATPase, and the
other encoding a site-specific DNA-binding protein recognizing a set of direct repeats upstream of the
genes. We have purified the proteins and begun to characterize their properties and role in plasmid
segregation. The project will involve complementary molecular biology, biochemical and biophysical
approaches in parallel with fluorescence microscopy to visualize protein and plasmid positioning,
trafficking and segregation in the cell.

The Department of Biology at the University of York is committed to recruiting extraordinary future scientists regardless of age, ethnicity, gender, gender identity, disability, sexual orientation or career pathway to date. We understand that commitment and excellence can be shown in many ways and have built our recruitment process to reflect this. We welcome applicants from all backgrounds, particularly those underrepresented in science, who have curiosity, creativity and a drive to learn new skills.