3Rs Day – 8th December 2023
Welcome from the Named Person Responsible for Compliance (NPRC)
Introduction from the Chair of AWERB
Applying the 3Rs to improve the rigour & reproducibility of animal studies
ABSTRACT: How many of us can honestly say that we put equal effort into implementing all 3Rs - replacement, reduction & refinement? In truth, the answer is likely to be not many. Why? Well because each ‘R’ presents different challenges & requires different skills to deliver in practice. For example, replacement is about doing something rather than nothing, requiring creative thinking, a willingness to challenge the status quo & resilience. Reduction is in part about good experimental design, but also requires excellent research planning & project management skills. Refinement used to be solely about minimising suffering but as our knowledge & understanding of animal welfare has grown, expectations have evolved. Refinement these days requires a meticulous attention to detail plus an awareness & understanding of the flaws or limitations associated with current research models, methods & approaches. So, ‘implementation of the 3Rs’ may be a familiar phrase to us all, but it does not happen by chance, or without effort. This presentation will reflect upon the challenges that each of the 3Rs present & how their implementation can enhance efforts to improve the rigour & reproducibility of animal studies. The range of ways in which each ‘R’ can be executed will be discussed & freely available tools created to support implementation of 3Rs in practice will be highlighted.
Supporting the adoption of replacement technologies in preclinical studies: an NC3Rs perspective
ABSTRACT: the presentation will summarise some of the successful replacement technologies funded by the NC3Rs and explain how institutions can help promote the adoption of alternative methodologies. It will also give an overview of the newly launched RIVER recommendations, designed to support rigorous reporting of in vitro studies.
Reducing and Replacing Glioblastoma Animal Models: Development of an Ex Vivo Organotypic Brain Slice Culture System for Long-term Glioblastoma Tumour Studies
ABSTRACT: With funding from AWERB, we will develop an organotypic brain slice ex vivo model for glioblastoma, specifically designed for longitudinal studies, with the ultimate goal of reducing and potentially replacing in vivo glioblastoma models. Our initial focus is to assess the viability of the ex vivo model over time, laying the foundation for its application in longitudinal studies. Once we establish protocols for the sustained culture of hippocampal sections, we will proceed to evaluate their effectiveness in studying tumour development and growth following the implantation of patient-derived glioblastoma cell lines. We anticipate that the AWERB funding will help us generate crucial pilot data that will support future funding applications.
Refining intra-tracheal dosing in rats
ABSTRACT: Intratracheal dosing is commonly used for toxicity tests in experimental animals. However, this technique can also be used for direct delivery of substances to the lungs to investigate their potential therapeutic effect on lung diseases such as pulmonary arterial hypertension (PAH). Our project aims to investigate the therapeutic effect of a microRNA, miR-96, on the PAH by means of direct delivery to the lungs using intratracheal dosing. The intubation process requires the animal to be immobilised using anaesthetics. Initially, we had used ketamine–medetomidine to induce anaesthesia in the rats prior to dosing. However, due to its long-lasting anaesthetic effect and its potential impact on the welfare of the animal, we decided to refine the intratracheal dosing. Using an isoflurane inhalation system allows for better control of the anaesthetic depth and sufficient time to perform the intratracheal procedure and results in a faster recovery with no or minimal side effects on the rat.
Three-dimensional cell culture systems using scaffolds, organoid and ex-vivo models
ABSTRACT: There is an urgent need to identify novel therapies for glioblastoma, a primary brain tumour with dismal prognosis. Preclinical studies using commercial glioblastoma cell lines in simplified in vitro two-dimensional models, three-dimensional model devoid of extracellular matrix and murine models have identified numerous targets capable of inhibit cell viability and tumour growth. Disappointingly, most therapies identified have fallen short of translating into clinical success. This discrepancy between preclinical studies and clinical response may arise from the utilization of preclinical models that inadequately mirror the complexity of the clinical disease, thereby lacking predictive value. In a concerted effort to enhance the likelihood of identifying effective treatments resulting in improved patient outcome, we and others, have directed our focus toward developing novel preclinical models that better encapsulate the clinical scenario, thereby augmenting their predictive value. This presentation will provide an overview of the current state-of-the-art preclinical models with a focus on glioblastoma, emphasizing the necessity for patient-derived cell lines and three-dimensional models that better represent clinical disease in drug development pipelines.
Speaking to the public about your research
ABSTRACT: How well does the public understand the 3Rs? What can we do to improve understanding and why should we bother? The speaker will discuss the power of public engagement in shaping popular opinion and what challenges may lie ahead.
Benefits of a Rat Play Pen
ABSTRACT: we will share – using videos and photos - our own experience of making a DIY rat play pen and of all the various benefits (for animals and humans!) that we have found it brings.
How Preclinical Imaging Systems Can Aid Your Research – And Introducing Something New
ABSTRACT: Revvity provides a range of preclinical imaging systems, including the IVIS optical imaging systems and the Quantum GX2 micro-CT system. In addition to this, the Vega is the newest member of the preclinical imaging portfolio. The Vega is an automated hands-free ultrasound system with a range of features which allows users to use its unique features to address specific research questions. This talk will introduce these systems & their features, their associated applications, and how they abide with the principle of the 3Rs.
Taking experimental hydrogel models of breast cancer through to a successful commercial product (with a few unexpected sideways jumps!)
ABSTRACT: I have always been fascinated by the extracellular matrix. I have a particular interest in glycosaminoglycans (linear sugars), but the concept of something outside of cells that can influence cell behaviour, but which is formed as a product of the result of a huge array of gene products and subsequent enzyme activities is something that really captures my imagination. Similarly, I’ve always had a huge respect for the application of animals in research. Working on models of early development, I could appreciate how much we could learn but also just how significant some of the differences were between these and humans. We were fortunate to win NC3Rs funding to develop simple peptide hydrogels as models of the extracellular matrix. Building on a successful project we used additional funding to further develop the hydrogels for additional applications and to learn from other users as to how we could improve the translatability of the technology. Eventually, we were able to commercialise our hydrogels, taking advantage of the ICURe programme to allow a PhD student from the group to explore their new-found interest in entrepreneurship. I’ll share this journey, it’s not the only route and we’ve still got a long way to go, but it’s been hugely fun as well as challenging so far.
Three (Rs) Tips for Statistical Analysis
ABSTRACT: Statistical analysis can help refine experiments, reduce the number of individuals required to establish a result, and to gain sometimes unexpected insight into experimental data. In this presentation I will offer three tips based around power calculations, ANOVA, and communication, that might help you use statistics - and statisticians! - more effectively in your research.
Many of our scientists are at the forefront in the search for and use of strategies to Replace the number of animals used in biomedical research. This includes the use and/or development of in-vitro techniques, in-silico models, microfluidic systems, organoids, etc, as well as the use of less sentient models (known as partial replacements). Below are just a few examples of this research effort performed within the University or in collaboration with colleagues at other Universities:
Under construction
Under construction