Women in Science: Using flies to fight cancer
My research group is interested in cell growth and cancer – we work on human cancer cells, but many of our ideas have come from studying growth in flies. You may at this point be wondering why we would want to use fruit flies to understand human cancer. I teach medical students here in Oxford, and although many also initially query the relevance of using flies to understand human disease, they tend to become convinced of this during the course of their degree. I hope that this short blog will serve to give you a flavour of how work with flies continues to make important contributions in the fight against cancer.
Flies and humans are on the face of it very different. But this isn’t the case if we look at the instructions for making these animals, which are contained within their genes. Remarkably, around 70% of the genes involved in human disease are shared with flies. The surprising level of similarity in how humans and much simpler organisms have been put together has meant that we can use flies as so-called ‘model organisms’ to work out how genes work in flies and humans.
People have been using flies to understand how genes work for over a hundred years, long before we actually knew about DNA. During this time, a lot of tricks have been developed that make this work particularly helpful.
Studies with flies have been remarkably successful in highlighting how the products of genes, proteins, work together in a sequential manner to transmit a message or signal from cell to cell or within a cell. These sets of proteins and the genes that make them are commonly referred to as a ‘signalling pathway’ and these pathways control how our cells behave – actually most of the signalling pathways that play important roles in cancer were first found in flies.
It was the work of a remarkable woman, Christiane Nüsslein-Volhard, and her colleague, Eric Wieschaus, that set the groundwork for much of our current understanding of signalling. She undertook an amazingly ambitious experiment in flies looking for all the genes involved in development. These genes were shown later to link together in a series of signalling pathways, and most of these pathways have since been shown to be affected in human cancer. She was awarded a Nobel Prize in 1995 for this work based on a surprisingly simple idea, which through clever experimental design and hard work, led to a whole series of completely unexpected findings.
In the US, after I finished my first degree in Chemistry, I had the good fortune to work in a couple of fly labs at Harvard and MIT. I had last studied biology when I was 16, and so this was quite a steep learning curve, but proved to be a serendipitous start to my current career. In Boston, there is quite a concentration of ‘fly labs’ with some amazingly creative scientists. I remember being struck by the way in which fly workers had managed to get very clear, but unexpected insights into a wide range of biological processes, such as learning and ageing, just by carefully studying flies that didn’t seem to do these things normally.
These labs tended to have quite a mix of men and women aspiring to establish new fields of research that would enable then to develop a career as future leaders in their areas, while frequently also juggling commitments to their families. This was a great place for a young impressionable scientist to start out and an environment that really inspired me to dream about leading my own research group one day, while still having a family, even though I knew it would not be a straightforward process.
My research group currently works both with flies and with human cells, which we grow in dishes, trying to understand how growth is controlled, particularly by what we eat.
I became interested in this problem when we discovered a gene called PTEN in flies and found that it tells cells how much to grow. This finding was important, because at about the same time it became clear that PTEN didn’t work properly in the majority of human cancers. Work from many fly labs around the world has since highlighted a signalling pathway that regulates the size of cells, not only in flies, but also in people that is kept in check by PTEN. This pathway is regulated by hormones that look like insulin. Levels of these hormones are increased as we ingest more nutrients.
Remarkably, humans also share another growth-controlling system, which is also found in very simple organisms like baker’s yeast. It is controlled directly by nutrients, but also links up to the pathway controlled by PTEN. Again, using the fly approach, we have found a nutrient-sensing molecule that controls this second pathway and is very active in cancer cells. We are currently working with medical doctors to see if we can selectively target cancers by blocking this sensor with drugs.
Many people have a fascination in understanding how animals work and why they look so different from one another – that’s why David Attenborough is so popular. I am going to be bringing some animals along to my talk. I’ve been fortunate enough to make a career out of studying animal biology, while thinking about healthcare problems.
Dr Deborah Goberdhan is speaking at ZSL and L’Oréal-UNESCO’s Soapbox Science on Southbank, 16th July 2012 www.zsl.org/soapboxscienceTagged in: cancer, cell growth, Christiane Nüsslein-Volhard, Eric Wieschaus, flies, fruit flies, health, research, science, women
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