Institute for Cell and Molecular Biosciences Newcastle University

Supervisors: Professor Bernard Connolly
Institute: Institute for Cell and Molecular Biosciences
Funded by: BBSRC
Duration of the award: 4 years (MRes Medical and Molecular Biosciences followed by a three-year PhD)

Hyperthermophilic archaea possess a family B and a family D DNA polymerase. Family B polymerases are widely distributed and are usually involved in DNA replication. Family D enzymes are unique to the archaea and poorly characterised.

Hyperthermophilic archaea possess a family B and a family D DNA polymerase. Family B polymerases are widely distributed and are usually involved in DNA replication. Family D enzymes are unique to the archaea and poorly characterised.

Archaeal family B polymerases stall DNA replication when they encounter the pro-mutagenic base uracil. The structural basis of uracil recognition has been established but, without genetics, evaluating the physiological role of this novel property has been impossible. With the discovery that Thermococcus kodakaraensis (Tk) is amenable to genetics, this barrier has been removed. It is proposed to change valine at position 93 of the polymerase gene to glutamine, an alteration that abolishes the ability to recognise uracil. The mutagenic consequences of this V93Q substitution in vivo in Tk will be determined to test directly the hypothesis that recognition of uracil is a surveillance mechanism that initiates a novel archaeal DNA repair pathway.

Little is known about the family D polymerase. Intriguingly, this protein also responds to uracil, although in a manner completely different to the B polymerase. A profound reduction in DNA synthesis is observed with uracil in both primer and template strands. This polymerase may possess a uracil-dependent strand separation activity. It is proposed to fully characterise the DNA recognising properties of polymerase D, particularly with uracil and other damaged bases using biochemical, structural (X-ray crystallography) and genetic approaches.

Eligibility and Value of the Award
Depending on how you meet the BBSRC’s eligibility criteria, you may be entitled to a full or a partial award. A full award covers tuition fees and an annual stipend of £13,590 (2010/11). A partial award covers fees only.

Person Specification
You should have, or expect to achieve, a minimum of an upper-second-class Honours degree, or equivalent, in biochemistry or molecular biology.

Further Information and How to apply
For further information on how to apply please go to www.ncl.ac.uk/pg/fund/cmb77
Funding information

Funding applies to:
UK applicants only