EASTBIO Tying up loose ends: studying the molecular interactions that protect chromosome ends

Telomeres are nucleoprotein complexes that protect the ends of chromosomes, thereby preventing DNA damage and genome instability. Telomere-capping proteins pay a key role in this protective mechanism and mutations in these genes are associated with premature ageing and cancer. Interestingly, chromosome ends are found as single-stranded DNA (ssDNA). The G-rich strand of telomeric ssDNA can form secondary structures, including guanine quadruplexes (G4s), that influence telomere stability. To regulate this, all organisms encode Protection of Telomere (POT) proteins, but how these proteins manipulate telomeric G4s remains poorly understood. This project focuses on the structural and functional characterization of the protection of telomeres (POT) machinery using C. elegans as a model organism given its genetic tractability. C. elegans encodes three different POT proteins but their specific roles and whether they act synergistically to maintain telomere stability is largely unknown. By using C. elegans we will be able to combine genetics with biochemistry and single-molecule microscopy to visualize in real time single POT proteins processing telomeric G4 structures. 

Studies in model organisms established the paradigms for human telomere biology and continue to uncover novel telomere components and regulatory mechanisms. A PhD student working in this project will master molecular and structural biology methods, genetic tools, and single-molecule imaging techniques to determine how C. elegans POT proteins interact with telomeric DNA  sequences. The PhD project provides a broad range of interdisciplinary skills at the interface between microscopy, biophysics, genetics and molecular microbiology that are eagerly sought in both academia and industry careers. The student will have multiple opportunities to present results both at local, national and international level and will also benefit from the array of transferable skills training and relevant courses offered for career development through the Eastbio and St Andrews GradSkills programmes.

The successful candidate should have a 1^st-class honours BSc and/or MSc in Biophysics or Biology relevant areas, research experience, and enthusiasm for interdisciplinary research. Candidates should contact Prof Carlos Penedo ([Email Address Removed]) or Dr Helder Ferreira ([Email Address Removed]) to discuss their application and perspective on the project.  

HOW TO APPLY

Application instructions can be found on the EASTBIO website- http://www.eastscotbiodtp.ac.uk/how-apply-0

1)     Download and complete the Equality, Diversity and Inclusion survey.

2)     Download and complete the EASTBIO Application Form.

3)     Submit an application to St Andrews University through the Online Application Portal

Your online application must include the following documents:

-         Completed EASTBIO application form

-         2 References (to be completed on the EASTBIO Reference Form, also found on the EASTBIO website)

-         Academic Qualifications

-         English Language Qualification (if applicable)

Unfortunately due to workload constraints, we cannot consider incomplete applications. Please make sure your application is complete by Monday 5th December 2022.

CONTACT

Queries on the project can be directed to the project supervisor.

Queries on the application process can be directed to Jess Fitzgerald at [Email Address Removed]

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