Lead supervisor: Prof Daniela Barilla (Department of Biology)
Co-supervisors: Dr Paul Fogg (Department of Biology) and Dr Steven Quinn (School of Physics, Engineering and Technology)
The student will be registered with the Department of Biology
Antibiotic resistance is a major threat to human health worldwide and a major societal problem resulting in millions of fatalities globally each year. This is expected to rise to 10 million per year by 2050 if not tackled. Resistant ‘superbugs’ result either from mutations within bacterial chromosomes or horizontal transfer of resistance genes that often are present on mobile genetic elements such as plasmids.
Low-copy number plasmids responsible for antibiotic resistance employ sophisticated strategies to ensure faithful distribution at cell division. These plasmids encode two proteins, an ATPase and a DNA-binding protein, which assemble into a minimalist DNA segregation machine. This protein complex interacts with the chromosome and drives the plasmids to defined subcellular addresses. When this systems malfunctions, the plasmid is lost, resulting in an antibiotic-sensitive bacterial population. Thus, investigating plasmid segregation mechanisms can lead to the discovery of novel drug targets.
Our model system is a multidrug resistant plasmid, which replicates in Escherichia coli. The plasmid encodes two proteins that form a complex responsible for maintaining the plasmid in the cell. We have proposed a Venus flytrap model as a mechanism for plasmid segregation, which predicts that the plasmid is captured within a three-dimensional cage-like matrix formed by one of the proteins.
This project will investigate the interaction of the segregation proteins and the dynamics of complex assembly at single-molecule level, using multidisciplinary cutting-edge approaches at the physics- biology interface. You will familiarise with molecular biology, biochemistry, genomics and biophysics techniques. These will include molecular cloning, mutagenesis, protein-protein and DNA-protein interactions, single-molecule Förster Resonance Energy Transfer (FRET), crosslinking, Mass Spectrometry (MS) and chromosome conformation capture studies (Hi-C) to map the physical connections between plasmid and bacterial chromosome.
You will be supported and guided by two supervisors based in the Department of Biology and one supervisor based in the Department of Physics. Both Departments host state-of-the-art technology facilities that your research project will benefit from. As a BBSRC DTP student, you will also attend several in-house graduate skills training courses and the studentship includes a budget for attending scientific conferences and meetings. All the supervisors are involved in outreach activities, and you will be encouraged to become involved in these opportunities.
The Department of Biology holds an Athena SWAN Gold Award. We are committed to supporting equality and diversity and strive to provide a positive working environment for all staff and students.
The WR DTP and the University of York are committed to recruiting 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 we 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.
Entry Requirements: Students with, or expecting to gain, at least an upper second class honours degree, or equivalent, are invited to apply. The interdisciplinary nature of this programme means that we welcome applications from students with any biological, chemical, and/or physical science backgrounds, or students with mathematical background who are interested in using their skills in addressing biological questions.
Programme: PhD in Mechanistic Biology (4 years)
Start Date: 1st October 2023
Interviews: Friday 10 February 2023 or Monday 13 February 2023. Please keep these dates free.