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Combining molecular genetics and biochemistry to explore the biology of chromosomal DNA replication in the Archaea

  • Full or part time
  • Application Deadline
    Sunday, December 01, 2019
  • Competition Funded PhD Project (Students Worldwide)
    Competition Funded PhD Project (Students Worldwide)

Project Description

The Archaea constitute the third domain of life on Earth, comprise an estimated 20% of the planet’s biomass and make a major impact on both biosphere and atmosphere. Despite this however, they remain relatively understudied. This project is centred on understanding how archaeal cells maintain the integrity of their genetic information, with particular emphasis on exploring questions of protein structure, function and regulation within the archaeal chromosomal DNA replication machinery. Recent studies indicate that eukaryotic life emerged from an archaeal ancestor: therefore, in addition to showing how archaeal cells replicate their chromosomes, the work has the potential to provide insights into the evolution of replication protein function during eukaryogenesis (the evolution of eukaryotes).
The student will utilise the halophilic (salt-loving) archaeon Haloferax volcanii as a model system to explore DNA replication biology. Previously, the group has genetically and/or biochemically characterised a number of conserved replication factors in isolation, such as the MCM helicase (1), multiple single-stranded DNA binding proteins (2) and the sliding clamp PCNA (3). The aim of this challenging project is to integrate this work by purifying replisome complexes from cells, determining their composition and exploring the in vivo consequences of disrupting their structure in a targeted manner, thereby gaining novel insights into the molecular machinery of chromosome replication in archaea and how this may have evolved.
The student will acquire skills in molecular genetics, microbiology, biochemistry and bioinformatics.

Funding Notes

Eligibility requirements: A good BSc (Hons) degree (2:1 or above) or equivalent in molecular biology, molecular genetics, microbiology, biochemistry or a related subject is essential. A research Masters degree in an area of biology related to the project is desirable.
Funding source: School of Biology.
Duration: 3.5 years fees and stipend.

References

1. Kristensen, T.P., et al. (2014) The haloarchaeal MCM proteins: bioinformatic analysis and targeted mutagenesis of the β7-β8 and β9-β10 hairpin loops and conserved zinc binding domain cysteines. Frontiers Microbiol, 5, 123.
2. Skowyra, A. and MacNeill, S.A. (2012) Identification of essential and non-essential single- stranded DNA-binding proteins in a model archaeal organism. Nucleic Acids Res, 40, 1077-1090.
3. Morgunova, E., et al. (2009) Structural insights into the adaptation of proliferating cell nuclear antigen (PCNA) from Haloferax volcanii to a high-salt environment. Acta Cryst D, 65, 1081-1088.

How good is research at University of St Andrews in Biological Sciences?

FTE Category A staff submitted: 50.45

Research output data provided by the Research Excellence Framework (REF)

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