Using in vitro techniques to understand how resource competition between cells can drive metastasis in cancers – an experimental evolution approach
Department: Biomedical Sciences
Supervised by: Dr Tiffany Taylor
Metastasis – the progressive spread of malignant cells away from its origin in order to colonise new tissues – is the most deadly aspect of cancer, and therefore understanding the processes which encourage cell movement are of integral interest to the field. From the cancer’s perspective, metastasis offers the opportunity to escape deteriorated patches, and colonise unexploited, healthy tissue. Dispersal theory has been applied to cancer research, giving evolutionary explanations for trends in cell motility via a Darwinian fitness approach. Such theory predicts that increased competition between cells, via factors such as resource depletion, should promote dispersal and thus encourage metastasis. We aim to test this empirically using an experimental evolution approach. Similar studies have been used successfully in bacterial systems to help illuminate the evolutionary processes important in determining dispersal patterns, and cancer systems share similar empirical tractability. The student will follow populations of cancer cells in vitro under varying nutrient levels in order to investigate how resource competition affects motility of cancer cells. Firstly, he/she will investigate if cell migration away from resource depleted areas is dependent on positive chemotaxis. In addition, he/she will determine whether dispersal confers an advantage in conditions of increased competition (dispersing cells will have access to more resources which are quickly depleted around the densely populated tumour) by comparing the density (fitness) of cells which are motile to those which are non-motile under varying nutrient concentrations. This is a stand-alone project and offers a good opportunity of authorship for the successful candidate.
The student will spend 1-2 weeks on the first stage of the experiment – growing spheroids (artificial tumours) under varying nutrient conditions and following motility of cells. Weeks 3 – 5 will be spent on the second stage of the experiment – attempting to determine potential fitness advantages of dispersal under increased resource competition. And finally, week 6 will be spent analysing data, presenting the research project to the lab group and writing a report for submission. The student will be given feedback in these key areas of research enabling them to develop analysis and communication skills. Specifically, for this project the student will grow spheroids in vitro (using specially coated dishes which prevent them from adhering to the surface, cells will consequently attach to each other and therefore grow into spheroids); he/she will then transfer these spheroids into dishes where they can stick down (which allows motility behaviours to be expressed), and then look to see if the cells start moving away from the main mass of cells. Using time-lapse microscopy it is possible to generate movies of cells moving around and then quantify the cell migration by tracking the cells. These tracks can tell us how far each individual cell has moved, at what speed and whether it is moving randomly or displays biased non-random movement (directional).
The placement will be based entirely in Reading. The successful candidate will have a keen interest in biomedical sciences and evolutionary biology, with an appreciation for evolutionary medicine and its potential applications. Some previous laboratory experience is preferable, although training will be provided.
More generally, the student will benefit from learning skills in: • Tissue culture: learning how to grow artificial tumours in vitro. • Experimental evolution: learning how to determine fitness parameters in order to understand the evolutionary consequences of controlled selective pressures. • Statistics: performing appropriate statistical analyses for experimental design. • General skills: towards the end of the placement the student will be required to present the findings from the project and provide a brief written report on what was done. The student will also learn a number of transferrable skills such as teamwork, presentation and communication.
University of Reading, Hopkins Laboratories, Whiteknights campus
35 hours per week (full-time)
Monday 09 July 2012 - Friday 17 August 2012
Applicants should submit a CV and a covering letter by email to Dr Tiffany Taylor, describing your suitability to the project and why this particular project is of interest. The deadline for application is 17:00 on Friday the 9th of March. Interviews will be held on the 15th of March.