Tumor spheroid modelling
Principal supervisor: Dr Gib Bogle - firstname.lastname@example.org
A stipend for this project will be paid under Marsden Grant funding:
Tuition fees will be covered and the successful applicant will receive $25,000 p.a.
The tumour spheroid, which is grown in vitro from human tumour cells, is a very powerful cell culture model in cancer research. All tumours are initially avascular, and as the cells multiply the tumour core becomes hypoxic. Bill Wilson’s team at the Auckland Cancer Society Research Centre (ACSRC) develops hypoxia-activated prodrugs (HAPs), compounds that have cytotoxic activity switched on when taken up by a hypoxic cell. Spheroids provide an important way to test these drugs, and to explore the influence of the factors that determine their effectiveness.
Agent-based spheroid model
In the agent-based approach each cell in the aggregation is simulated as a separate entity that responds to its microenvironment. A preliminary agent-based model (ABM) for tumour spheroids has been developed, simulating cell growth, division and death taking into account the diffusion and consumption of oxygen and nutrients.
The first goal is to calibrate and validate the ABM on the basis of data from tumour spheroid growth experiments with a range of medium conditions. Once the model has been shown to be capable of reliably predicting the results of these growth experiments, it will be extended to incorporate drug effects, again validating against experiments. Since radiotherapy is ineffective against hypoxic cancer cells, we are very interested in exploring therapeutic protocols that combine radiation and HAPs, and killing by radiation will also be implemented in the model. At this point we will be able to design (and test through experiment) optimal combined treatment protocols.
This project will break new ground in cancer modelling – there are currently no published studies on the 3D agent-based simulation of drug-induced killing of tumours. Those models of drug therapy that have been published are continuum-based, incapable, we believe, of achieving the level of detail and realism that the agent-based approach provides. Our opinion seems to be shared by the Marsden reviewers, one of whom wrote: “This proposal is original and has significant merit: Developing a pre-clinical 'in vitro-in silico' drug/RT testing platform would have obvious benefit for integrative oncology research as well as, potentially, for the development of new treatment paradigms; this would be an accomplishment beyond Auckland or NZ, rather it would have an impact on the cancer modeling field itself.”
We are looking for a very good student, someone with strong mathematical, computational modelling, and programming skills. Interest in and willingness to learn basic cell biology is also important – this project is highly interdisciplinary, and will involve working closely with Dr Kevin Hicks, Professor Bill Wilson and the experimental team at the ACSRC.
Project added: 6 October 2014