Improve cross-talk, fewer mouse models, and coconuts

This week the NC3Rs and the Society of Biology hosted a joint symposium in London to showcase and discuss some of the latest advances in 3Rs research. Featuring speakers from a range of disciplines, the symposium covered improvements in the efficiency of animal models and techniques to reduce the reliance on in vivo approaches. Dan Richards writes about some of the highlights, and speaks with Professor Matthew Walker, UCL who is researching treatments for epilepsy.

coconut


Minimising the use of mouse models, but maximising the information you get out of them was the key theme of Wednesday’s NC3Rs and Society of Biology joint annual symposium. There seemed to be real sense of shared ownership over the 3Rs principles and it was clearly apparent throughout the day that cross-discipline work can drive real advances. The meeting wasn’t just about data, but ideas and beliefs.

To cover the whole programme in one blog post wouldn’t really do it justice, so we’ll be seeing some of the speakers offering their own thoughts to our blog over the coming weeks. But I’d like to share some of the ideas that chimed a cord with me, and I’m sure a lot of the early-career researchers and principal investigators who attended.

Dr Steve Renshaw, University of Sheffield, presented research on a model of inflammation in zebrafish larvae, advocating this model over mouse models and suggesting that it may be possible to bypass mouse models completely for respiratory research and go straight into the clinic from the zebrafish model. He described how it all boils down to neutrophil biology, and overcoming the challenges presented in cell culture and mouse models to understand their molecular mechanisms and find new drug targets.

Dr Renshaw showed us how neutrophil-rich zebrafish larvae are space-saving and cost effective in comparison to mouse models, with a transgenic line being far easier and quicker to prepare. Since three larvae can fit into a single well of a 96-well plate, this model can be used with ease for genetic screening, revealing important information that doesn’t necessarily emerge from other systems.

He also suggested that if it wasn’t possible to bypass the mouse completely, then using zebrafish larvae can certainly better inform further research using mouse models, changing how researchers approach the development of treatments for lung conditions.

Professor Owen Sampson, University of Glasgow, discussed using the Drosophila midgut, describing it as a “wonderful model of intestinal regeneration” for studying colorectal cancer, helping to reduce the use of mammalian models that would typically be needed. His talk focused on the genetic aspects of this research and his efforts in deleting the Apc gene in the fly, describing the many common features it shares with mammalian intestinal tissue, including stem cell and progenitor populations. Interestingly, the first paper describing this work in the Drosophila was published in 2007 and is already translating very quickly into clinical research, without a massive need for animal models.

Dr Tracey Newman, University of Southampton, called for more communication in the modelling community, saying scientists need to talk more, not just between peers in the same discipline, but also between disciplines, for better cross-fertilisation and application of ideas, and to help with experimental design. Dr Newman gave us insights into the design and manufacture of a multi-chambered, in vitro cell culture system, which she described as “the next petri-dish” for researching central nervous system disease and injury. This can support compartmentalised growth in organised arrays of neuronal cultures for live/fixed imaging, and could really help to reduce animal use in a research area where around 370,000 rodents are typically used in the UK each year.

Dr Newman’s key message that we need greater cross-discipline communication echoed several points raised earlier in the day by mathematician Professor Philip Maini, University of Oxford, who covered mathematical and computational modelling of development and started by asking us the question “what is a model?”

Professor Maini’s photo of David Hasselhoff in his prime helped illustrate a generally held misconception that models mean different things to different people, and aren’t necessarily an accurate replication of all humans. He defined a model as simply a scaled down version to test a hypothesis, generate new hypotheses, help prioritise an explanation and improve our intuition. He showed how we can use mathematical modelling to increase our understanding at the basic scientific level to help reduce the number of experiments needed later down the line. But he cautioned that the role of mathematical modelling in the main is not to replace experiments.

Techniques for making the breeding and use of mice more efficient were also high on the agenda, with Dr Sara Wells from MRC Harwell discussing how efficient breeding can lead to massive gains in cost and time and help reduce genetic drift and the numbers of animals used overall. I asked Dr Wells what her top tip was for anyone breeding mice:

“Have a look at the background strain you are working on; take as much information about that background strain as you can and work out the breeding numbers very carefully. Constantly keep an eye on your breeding colony, because I believe that the way animals are bred and reared has a major impact on the phenotype they display.”

Professor Matthew Walker, University College London (UCL) spoke on searching for a new cure for epilepsy, and the approach being taken in slime moulds (Dictyostelium) to identify pathways and mechanisms of drug action to uncover new drug targets and compounds that overcome drug resistance and the side-effects sometimes seen with currently available drugs such as sodium valproate (Epilim). By doing the research in slime moulds in this way reduces the numbers of mammals used by thousands.

I caught up with Professor Walker in the coffee break as I wanted to find out more about his work and how coconuts fit into the research. You can listen to this interview in a podcast below.

There was a great deal more covered at the symposium, including a whistle stop tour from Professor Mark Lythgoe, UCL on how to image mice, focusing on some of his latest work using 3D MRI… but more on that, and the poster prize, in a later blog post.

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