Supervisors:
Dr James Wakefield
Prof Rob BeardmoreÂ
Cell division is a fundamental biological process, driven by the formation of a microtubule (MT)-based mitotic spindle that aligns the chromosomes and ensures their segregation. Research over the last twenty years has led to a list of gene products with roles in spindle formation. The challenge of post-genomic biology is to understand how these gene products work together to define biological process. We have developed methodologies, based on high-resolution fluorescence microscopy, coupled to image analysis, which allow us to quantify the generation and organisation of MTs during mitotic spindle formation in the model organism, Drosophila melanogaster. The goal of this project is to determine the molecular mechanisms underpinning MT organisation during the early stages of mitotic spindle formation, referred to as “coalescence”. In this process, molecular motor proteins sort, orient and slide MTs in relation to another, ensuring a bipolar mitotic spindle is formed.
In the first rotation, the student will combine biochemical and cell biological techniques, affinity-purifying an antibody raised against the kinesin-like protein Klp61F, which slides MTs during the early stages of mitosis. They will undertake high temporal and spatial cell imaging techniques, to obtain time-lapse movies of MT organisation, both in control Drosophila embryos and those injected with the anti-Klp61F antibodies. In the second rotation, they will be introduced to computational image processing and quantitative analysis techniques required to systematically analyse their data. By the end, they will have quantitatively analysed biological datasets, extracting key parameters such as MT dynamics ranging from MT bundling to directionality, in a statistically significant and objective framework.
The main body of the PhD will see the student disrupting the kinesin-like proteins known to function during spindle formation. For those for which antibodies are not currently available, the student will produce DNA constructs to allow the bacterial expression and purification of pure protein, in order to generate polyclonal antibodies for usage. Under the guidance of Prof Beardmore and Dr Metz they will expand on their computational techniques, gaining a deeper understanding of the numerical approaches and connections with the appropriate theoretical modeling.
Together, the fusion of these techniques will allow the student to address a fundamental biological problem and provide them with a unique and highly desirable skill-set, with expertise in experimental and theoretical biology, mathematics and computational techniques.
This project has been shortlisted for funding by the BBSRC South West Doctoral Training Partnership (DTP), a collaboration between the Universities of Exeter, Bristol, Bath and Rothamsted Research institute. This project is one of a number that are in competition for funding. Studentships will be awarded on the basis of merit. For further details about the programme please see http://www.bristol.ac.uk/swdtp/
Applicants for this studentship must have obtained, or be about to obtain, a First or Upper Second Class UK Honours degree, or the equivalent qualifications gained outside the UK, in physics, maths, engineering, or related degree, and have a demonstrated interest in the biological sciences. Programming and laboratory experience are desirable.
The studentship will cover a stipend at the standard Research Council rate (£13,726 per annum for 2013-2014), research costs and tuition fees at the UK/EU rate for students who meet the residency requirements outlined by the BBSRC (see http://www.bbsrc.ac.uk/web/FILES/Guidelines/studentship_eligibility.pdf).
To apply please go to the Apply button below.
Closing date Friday 10th January 2014