Nano Systems Biology

Research

Funding received from Breast Cancer UK

Breast Cancer UK has announced funding support to look at the potential endocrine disrupting effects of a range of commercially available pesticides. By using a hormone responsive, 3D human breast cancer cell model any effects on morphogenesis arising from these chemicals will be quantifiable. The effects of low dose mixtures of these chemicals both separately and in conjunction with oestrogen will be determined. This will highlight a key aim of Breast Cancer UK to understand the dangers of chemicals that co-exist in the environment and how they interact with the natural hormone cycle to create a potentially carcinogenic environment. The advantage of this model is that, it allows us to go beyond two-dimensional cell proliferation tests, as pioneered by our collaborators in Tufts University. These can be used to detect if a chemical behaves as a xenoestrogen: but there is a clear gap in available testing procedures, which do not allow the effects of chemicals on tissue development, which will give a pathological readout, to be studied without the use of animal experimentation.

Breast Cancer UK uniquely campaigns against dangerous chemicals in our environment that can increase the risk of breast cancer. The charity’s mission statement is Breast Cancer UK is dedicated to the primary prevention of breast cancer by reducing public exposure to the carcinogenic and hazardous chemicals in our environment and everyday products.

A 3-D tissue model of breast morphogenesis for replacing animals in testing for endocrine disrupting substances

This project is funded by the NC3Rs which gives grants to research projects aimed at replacing, refining and reducing animals in research. Support funding was also provided by Breast Cancer UK.

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MCF10A cells in 3D culture
Single MCF10A cells beginning the initial stages of collagen remodeling and structure formation. Cell actin is labeled green, the nucleus in blue and surrounding collagen in grayscale

Using human breast cells growing in artificial collagen gels we have successfully created models which can be used to watch the development of complex breast structures from single cells in real time. In addition a breast cancer model which retains hormone sensitivity in culture conditions has been used to create a sensitive test for xenoestrogenes. These chemicals can have potential endocrine disrupting effects during development and lead to an increased risk of cancer. By creating models that behave like tissue in the body a large number of animal experiments can be replaced.
Specialised microscopy techniques were used to image collagen fiber re-modelling during breast structure formation in living cells over a number of days and in some cases weeks. The video below shows a tubule forming from human MCF10A cells over a period of 5 days. Collagen fibers are coloured green. Fiber alignment takes place in the direction of cell growth and between neighbouring structures. Eventually a network of tubules is formed characteristic of breast tissue.

    Multiscale Applications on European e-Infrastructures (MAPPER)

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    Multiscale Applications on European e-Infrastructures (MAPPER)

    http://www.mapper-project.eu

    The main aim of MAPPER is to develop tools, software and services that allow two modes of multiscale computing to be executed on and across European e-Infrastructures, in a user friendly and transparent way. MAPPER also works with resource providers to develop policies that facilitate multiscale modeling and simulations.

    MAPPER is partly funded by Seventh Framework Programme (FP7/2007-2013) of the European Commission under grant agreement n° RI-261507.

Attached documents