CDT Lab Postgraduate Study

research projects | applications

research projects

Research in the lab is based around the study of plasmid replication and mobilisation in Staphylococcus aureus. Out of this has evolved interest in related rolling-circle replication mechanisms of plasmids and bacteriophages from other organisms; the interplay between the key enzymes which trigger these processes and their DNA targets, other enzymes involved in the maintenance of DNA which utilise covalent protein-DNA intermediates, and also the protein-protein interactions which occur subsequent to these events.

Our approaches are principally biochemical, using appropriate engineering to create a range of modified proteins (and substrates) to determine the individual steps of the various reactions. This is in close conjunction with structural studies, always aiming for visualisation of the three-dimensional structures of our molecules of interest, backed up with analysis in vivo to relate kinetic parameters with biological function.

While our progress in many of these areas is described elsewhere, prospective candidates will be interested in what we will be studying over the next few years. The very nature of scientific investigation makes that hard to list! But as a general idea, some of the current topics in the lab - and questions we would like to address - include:

  • Replication of pC221 and related plasmids:
    - alteration of initiator protein activity for novel applications;
    - engineering the interface between subunits of the initiator protein RepD;
    - exploiting the interaction between RepD and PcrA helicase at single-molecule level;
    - structural studies of multicomponent complexes with RepD;
    - structural studies of the replication initiator protein of filamentous phages;
  • Mobilisation of pC221 and related plasmids:
    - characterisation of the accessory protein:relaxase interaction;
    - identification of specificity determinants between the relaxase and oriT;
    - determination of accessory protein structure both alone and in complex with DNA;
    - the role of replication signals in recovery of ssDNA transmitted to the recipient;
    - interplay with factors specified by co-resident, self-transmissible plasmids;
  • Type II topoisomerases of the Staphylococci:
    - domain structure of the nicking-closing subunits GyrA and GrlA;
    - comparative antibiotic susceptibility between the two A subunits;
    - characterisation of the interactions of novel antibiotics with the holoenzyme forms;
  • Conjugative Transposons of the Staphylococci:
    - characterisation of a candidate relaxase;
    - key differences defining mobilisation instead of replication;
    - DNA targets and accessory protein interactions in the mobilisation process;

If these approaches and topics are of interest to you, we would like to hear from you! But please read the rest of this page first...


All applications for postgraduate study (PhD, MSc, MRes) should be directed to the relevant pages of the Faculty Graduate School and Astbury Centre for Structural Molecular Biology:

These web sites include information about making your application and all necessary links for the application process (both paper and online). Applications are best submitted directly (not to me) before the year end, prior to entry the following October for successful candidates. Make sure you include a covering letter with your application, stating which area of our work is of interest to you (and why!), and also what you hope to gain from a period of study in the lab.

Funds for studentships in our lab are available in competition with other members of the Astbury Centre for Structural Molecular Biology. A range of scholarships is available for International students - please see the GradSchool web site for more details. Self-funded candidates are welcome to submit their applications at any time - but don't forget, research is expensive!

We are participants in the Astbury Centre's Wellcome Trust Four Year PhD Programme, and can offer rotation projects for such students in their first year as well as doctorate level study.

The Astbury Centre also offers BBSRC Doctoral Training Grants, for which funding is available for UK and certain EU students.

We are also participants in the University of Leeds Institute of Bionanosciences, and can offer a range of collaborative projects in this exciting area. Again, please specify in your covering letter which of these subject areas has prompted your application.

Good Luck!