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Maximising the 3Rs impact of NC3Rs-funded research: author and reviewer Q&A

26 Jul 2018

A method article published on NC3Rs gateway on F1000Research describes the process of making whole brain organotypic slices and explains how this method can be used to reduce and refine the use of animals in Alzheimer’s disease research.

In this Q&A, authors Cara Croft and Wendy Noble (CC and WN), and reviewer Claire Durrant (CD), talk about the 3Rs (replacing, reducing and refining); the NC3Rs gateway and their experience of open peer review. 

Cara Croft is a Postdoctoral Fellow at the Center for Translational Research in Neurodegenerative Disease at the University of Florida, USA. Her research focusses on determining mechanisms underlying neurodegeneration in Alzheimer’s and Parkinson’s disease using interdisciplinary approaches and identifying novel therapeutic targets.

 Wendy Noble studied for a PhD at University College London before becoming interested in Alzheimer’s disease during her first postdoc position in New York. Wendy returned to the UK in 2004 and is currently a Reader in Neuroscience at King’s College London where her group investigates the mechanisms underlying tau-associated neurodegeneration.

Dr Claire Durrant (née Harwell) is a postdoctoral researcher in the department of Clinical Neurosciences at the University of Cambridge. Her work focuses on using the organotypic hippocampal slice culture system to study mechanisms of synaptic disruption and loss in Alzheimer’s disease.

As one of our first NC3Rs gateway authors, what motivated you to participate? What were the differences, if any, in the way you approached this paper?

CC & WN: We had already published two papers from our NC3Rs funded project, which describe some of our findings using organotypic brain slice cultures to model aspects of Alzheimer’s disease. These papers illustrated how development of molecular pathologies in slice cultures relate to those occurring in vivo, showed that there are alterations in tau release in transgenic models relative to non-transgenics and also described how brain slice cultures were used to identify novel effects of compounds.

One of the limitations of these publications is that they are heavily focused on the results, and there was a limited amount of space for a detailed description of the methodology that we used. We prefer organotypic brain slice cultures to in vivo studies of disease because of its more rapid and higher throughput manner, which also reduces animal use. We were pleased to be able to share a detailed methodology through the NC3Rs gateway to encourage others to use these methods.

We particularly liked the format of the methods paper, as we could provide very detailed instructions about the materials we used; the methods themselves, as well as hints and tips for those trying these methods for the first time. It was an ideal format for us to outline the main 3Rs implications of our work and how these could be extended to other fields.

CD: I am a strong believer in the dissemination of methods to replace, reduce and refine the use of animals in scientific research. As such, I was delighted to be invited to review an article for the F1000 NC3Rs gateway. I have reviewed a number of papers before, but this was the first time my review would not only be made public, but also linked to my name.

That being said, I approached the review as I would for any article; checking the paper is of publishable quality and aiming to give feedback that would result in the best science moving forward.

As someone who works with the method described in this paper, I saw this as an opportunity to have an open conversation with the authors about their work and provide a forum where ideas could be discussed.

As part of a transparent invited post-publication peer review process, the NC3Rs gateway asks referees to assess whether the 3Rs implications in the article have been adequately described.  What benefits do you think this mode of peer review offers over the traditional model?

CC & WN: The F1000 post-publication peer review model is an attractive model since it allows transparent critique by experts who are in a position to comment on both the scientific relevance of the work in addition to how well it addresses the 3Rs principles. This was an important consideration for us when we decided to publish this paper.

We are keen that the 3Rs impact of our model are clearly outlined to other scientists, regulatory and ethics committees. The post-publication review allowed the opportunity for clarification of important points, ensuring that our message is clear to all readers.

CD: I think the open model of peer review allows for better discussion and debate on issues surrounding the use of animals in research. Usually the 3Rs are not the main focus of a publication, so the relevant descriptions are often relegated to a few sentences in the method section.

Asking the reviewers to directly assess the 3Rs implications helps raise the profile of this key principle. Having such conversations in a public forum will also allow multiple readers to think about and have their say on the best ways to ensure ethical use of animals in research.

In her review, Claire mentions that the methodology tips provided in the article are ‘very useful for someone seeking to perform slice culture experiments for the first time.’ Do you have any other advice for someone starting out in this field?

CC and WN: We greatly appreciated having Claire review this paper since she has significant expertise using slice cultures. Her validation of our manuscript is important to us as it shows that she believes our method description is valuable for those learning these methods for their own experiments.

Precision during the dissection is critical as it determines the slice viability, so we strongly recommend that anyone starting out should practise this element. Once plated, the slices are quite robust if properly cared for.

We encourage people to try these methods! Slice cultures are more advanced than single cell cultures and show accelerated phenotype development compared to in vivo studies. With the proper training and/or advice new researchers can rapidly gain meaningful data while also implementing the 3Rs.

 CD: Having trained a few people in the technique, I think the biggest factor for success is perseverance and practice! Aside from this, my main tips for improving slice cultures are: batch test your medium components; keep an incubator just for slices and be mindful that these cultures are sensitive to vibration; temperature fluctuation; contamination (if not handled aseptically) and lack of humidity.

Don’t be afraid to ask for advice from people who have more experience in the slice culture method as there are often lots of small tricks to make your life easier that are difficult to describe effectively in a paper.

What have you taken away from this experience?

CC & WN: We appreciated the opportunity to be able to provide a more detailed methodology to readers. We hope that the publication of our detailed methods will encourage other scientists considering using brain slice cultures to embark on these studies as an alternative to continuing with in vivo research.

We appreciated the insightful reviews which allowed us to improve our manuscript and are pleased that a reader can follow the entire process from initial acceptance. The F1000 publishing model with rapid post-publication open peer review will likely be taken up by more journals in future, and the hope is that this will enable a more considered review process.

Overall, we believe that the NC3Rs gateway will provide a carefully curated database of 3Rs research methods and reviews which will be of value to the scientific community for many years to come.

CD: I have found the whole experience incredibly encouraging as I can see how an open peer review model could be adopted more widely. It was interesting to see how different reviewers brought their own expertise and set of questions to the discussion.

Overall, the whole process felt like a collaboration to produce the best manuscript possible and I have very much enjoyed being a part of that. It gives me hope that we could be moving towards a more transparent, collaborative and interactive way of publishing.

The post Maximising the 3Rs impact of NC3Rs-funded research: author and reviewer Q&A appeared first on F1000 Blogs.

Click here to view the full article which appeared in F1000 Research