Ovarian cancer is the fourth most common cancer in the UK, affecting approximately 6,500 women each year.

Dr Barbara Guinn and her team at the University of Hull have identified a small protein, that has elevated levels in the earliest stages of ovarian cancer and limited to no expression in most healthy tissues. As the protein is small, it may also be excreted in patient urine and therefore has potential to be used as an accessible biomarker for early diagnosis  – they hope to investigate this potential.

Barbara and her team want to investigate how the protein is contributing to the early development of ovarian cancer but there is a lack of human-centred early-stage cancer models. The aim of this project is to produce an epithelial cell line that they can add the protein to. This can be used to develop a new model for studying early-stage epithelial ovarian cancer and share proof of principle with the research community and facilitate ongoing research in the area. This model can be used in place of animal methods which are difficult to use to investigate early diagnosis due to the aggressive tumours induced. 

The team have already shown that targeting this protein in late-stage ovarian cancer has the potential to destroy late-stage ovarian cancer cells, however by this point the disease has spread, and a combination of other factors make it harder to target the protein effectively. This research will not only help clarify the role of the protein in early-stage ovarian cancer development but also determine whether the protein can be used to increase early-stage diagnosis and treatment of the disease.  

We are advocates of great science and believe strongly in the importance of medical research. Many people are alive today due to breakthroughs in medical treatments, but often these come at the cost of animal lives. 

By developing these new non-animal methods we not only support the transition to enable medical and scientific research to continue without the cost to animal lives, we are also helping to develop modern, human-relevant approaches. These approaches have the potential to provide us with more knowledge of human disease, how to diagnose them and how to treat them.  

Barbara Guinn and her team’s project will help explore the role of this protein in early-stage ovarian cancer as well as serving as a great example of an innovative, non-animal research approach that can be replicated and utilised by other researchers working in this area.

In this project, Dr Hisham Al-Obaidi, Prof. Simon Andrews, Dr Glyn Barrett and Prof. Vitaliy Khutoryanskiy aim to develop an innovative synthetic lab model that resembles the lung environment to effectively predict how medicine will act when given to humans.

Lung infections, especially lower respiratory tract infections, are leading causes of transmissible deaths worldwide according to the World Health Organisation (2020). The majority of patients who suffer from them have their lungs colonised by a particular strain of bacteria. These infections tend to have a greater impact on patients who already have existing lung problems such as cystic fibrosis (CF) or chronic obstructive pulmonary disease (COPD).

The bacteria Pseudomonas aeruginosa is the most common chronic lung infection in CF patients and lung failure is the main cause of death. P. aeruginosa has become resistant to many antibiotics used to treat infection and is also notoriously persistent in clinical settings due to its ability to form antibiotic-resistant biofilms. Biofilms are densely packed bacterial growing in communities on living or inert surfaces, surrounded by a matrix of polymers and other substances that help provide protection. The high level of antimicrobial resistance shown by P. aeruginosa biofilms is driving the need to develop new and more effective antibiotic treatments to combat it.

The most common current treatment, is the antibiotic ciprofloxacin (CFX). CFX is a broad-spectrum antibiotic which can be given orally or intravenously, however neither of these methods have the ability to deliver high concentrations of CFX to the lungs where it is needed. Delivering the drug through the body via these methods also causes side effects. Previous research by members of the team has identified that a CFX inhalable version of the drug would be of great interest as a non-invasive route to directly target the infection site.

Assessing the effectiveness of inhaled drugs is tricky and methods for doing this currently cannot replicate the physiological conditions of the lungs, including the effects of mucus and other lung surfactants (fluids) on the activity of the drug. This is particularly important when creating a model to study conditions with mucus abnormalities, such as CF. The most common animal ‘models’ used to research inhaled particles are rodents, such as mice. Mice have different airway physiology to us and do not naturally breathe through their mouth, so forcing them to inhale these drugs in an unnatural way not only causes suffering but does not provide a physiologically accurate model of the human lungs.

The researchers will use FRAME funding to create a model that should better simulate conditions in the lungs by using synthetic materials to resemble mucus. The team will be able to control the thickness of mucus to replicate different conditions inside the lungs, such as those seen in CF or COPD, adding P. aeruginosa to study the growth of biofilms and the effect of the mucus on the deposition and effectiveness of inhaled antibiotic treatments.

This project involving Dr Roger Domingo-Roca, Dr Joseph Jackson, Dr Helen Mulvana, and PhD student Lara Diaz Garcia at the University of Strathclyde looks to use multi-material 3D printing to develop new platforms to investigate the physics and biology of microvascular networks to help reduce the need to use of animals in the investigation of drug delivery and disease treatment, such as the treatment of cancer.

Cancer is the leading cause of morbidity and mortality worldwide accounting for about 10 million deaths in 2020. There are several ways of treating cancer, the most common ones being surgery, chemotherapy, and radiotherapy, independently or as adjuvants (supporting the primary treatment e.g., surgery). These treatments aim to damage cancerous cells and prevent them from growing and multiplying. While effective, these treatments do not selectively attack cancerous tissue but generally damage both healthy and malignant cells, leading to significant, severe, and undesirable side effects that patients must endure. This has led researchers to investigate alternative, less aggressive ways of treating cancer without compromising treatment effectiveness.

One of these alternative treatments is the use of ultrasound-driven microbubbles to target drug delivery. Microbubbles are injected into the bloodstream in conjunction with therapeutic agents to circulate systemically and are then locally stimulated by applying ultrasonic fields to deliver the drug to the tumour. This technology shows great potential to deliver drugs locally and reduce toxic side effects of the drugs on other cells, but there is a lack of understanding of how physical and biological parameters affect drug transport and delivery. There is also a need to better understand how they can be safely eliminated from the body and identify whether there are any issues with inefficient drug transport or delivery in practice. These combined issues are delaying the development of effective clinical treatments that use microbubbles for drug delivery.

In light of all the potential benefits that this microbubble technology will provide to cancer treatment, scientists are employing animal models to speed up their development, often mice. This approach raises a set of ethical and research issues that must be assessed: (i) the severity of the experimental procedures on the animals, (ii) working with uncontrollable environments, (iii) the limitations to reproduce physiologically relevant conditions that, at the same time, reproduce tissue-mimicking properties. These factors, together, hinder progress in this area of biomedical research.

This innovative project is based on the researcher’s belief that recent advances in 3D-printing technology and materials science will lead to the development of a platform that enables detailed study, testing, and analysis of novel cancer treatments in 3D-printed, physiologically relevant in vitro systems. The team has already demonstrated the potential of 3D printing to develop tissue-mimicking and functional materials that can be used to produce cost-effective, physiologically relevant models. The next stage is to develop these models, with the aim of replicating microvascular features where conditions within the body such as the effect of fluid flow or blood vessel diameter can be replicated.

The FRAME grant will help address the next key challenge in the project, which is the development of cell-compatible photosensitive materials to 3D-print microvascular-mimicking in vivo environments which may be used to study biomedical and bioengineering problems such as drug delivery and uptake and ultimately to investigate the effect of different biological and physical parameters on the effectiveness of ultrasound driven treatments such as MBs.

Jia Jhing Sia from Malaysia has just completed the penultimate year of her BA in Biomedical Sciences at the University of Oxford. She is carrying out her summer project at the Laboratory for Cerebral Ischaemia based at the John Radcliffe Hospital in Oxford under the supervision of Research Fellow, Dr Paul Holloway. Her project: ‘Delineating pericyte contribution to hereditary cerebral small vessel disease using organ on chip technologies’ aims to use in vitro, organ-on-a-chip culture systems to investigate the role of a type of cell called a ‘pericyte’ in diseases that affect the blood vessels in the brain, causing strokes and dementia.

Jia Jhing explains: “Neurological disease modelling is unfortunately an area that is still largely dominated by animal research and testing owing to the limitations of investigating human brains in patients, and the complexity of modelling the human central nervous system (CNS) in the lab. The urgent need to develop new, non-animal CNS models is highlighted by contradictory findings in animal models of neurological diseases. This is in the main due to the significant variation shown between different species and is reflected in the low success rate seen in clinical trials for drugs treating the nervous system. There is an urgent need for more human relevant models of the CNS to help investigate disease and predict the efficacy and safety of potential new drugs to treat the brain and nervous system.”

Sally Prior is studying for a BSc in Medical Biochemistry at the University of Huddersfield and hopes to one day study for a PhD in cancer biology. She is completing her summer project on the ‘Validation of a Novel Software Plugin for Analysis of 3D Models of Paediatric Glioma Cell Migration’ under the supervision of senior lecturer and Glioma Research Group leader Dr Anke Brüning-Richardson.

Sally explains: “Gliomas are a group of highly invasive cancers which originate in the brain or spine and are now the biggest cancer killers in children. Due to their invasive nature and re-growth after initial treatment ultimately leading to the death of patients, our research into gliomas centres on studying the effect drugs have on cell properties such as migration or invasion. This is to prevent recurrence of such cancers and promote patient survival. Currently, rodents are used to study the effect of cancer drugs in vivo, including within glioma research. Our laboratory has been developing a 3D invasion model to allow the reduction and hopefully replacement of such in vivo models. A software capable of analysing 3D generated effects of anti-migratory drugs has been developed alongside the 3D invasion model to allow the generation of clinically relevant data.”

William Hunt is studying for a BSc in Neuroscience with a professional training year at Cardiff University. Will’s project: ‘Using Computer Models as a Method of Replacing the Use of Animals in Neuroscience Research’ incorporates a review into computer modelling, artificial intelligence (AI) and machine learning, with a discussion around the application of these tools in specific areas of neuroscience research.

This project is again focusing on neuroscience – an area of biomedical research where we know some human conditions are not naturally occurring in animals, and therefore promising research findings are often not translating into progress in understanding of human diseases or progression in treatments. The continued popularity of animal-based research in some of these areas raises both ethical and scientific concerns. Will agrees, and says it inspired him to develop the idea for his summer project: “Since starting my placement year, I have gained a better appreciation for the vast use of animals in scientific research, especially within behavioural neuroscience. This has motivated me to explore and investigate the methods being developed in attempt to replace animal models. In particular, I came across in silico human-based computer models in research that are reported to produce results consistent with, or better than animal models.”

Our final winning student to introduce is Emma Turnbull. Emma has just completed the final year of her BSc Biomedical Sciences degree at Newcastle University. She is undertaking her summer project to create a novel (new) 3D lung model that can be used to study lung inflammation during infection before starting a MRes in Immunobiology this October. Her project titled: ‘Towards replacement of animals in lung inflammation research: developing novel 3D model of human lung inflammation in vitro’ is being supervised by Wellcome Trust Fellow Dr Polina Yarova, and co-supervised by Dr Kate Musgrave and Professor John Simpson, all based in the Translational and Clinical Research Facility at the Newcastle Faculty of Medical Sciences.

Emma says: “Lung infection and inflammation is one of the leading causes of death worldwide. Critically ill patients are especially prone to developing pneumonia, which often leads to lung failure, with no treatment currently available to rectify this. Multiple animal models have been used to mimic pneumonia, but animals are not humans, and results obtained using animals poorly translate into patients and raise ethical concerns. In response to this, several in vitro models of human lung were proposed. However, most of those models recapitulate some, but not all features of the human lung, forcing researchers to use animals to answer more complex questions, where interaction of multiple cell types is required.”

Lisa van den Driest is currently studying for a BSc (Hons) in Pharmacology and Microbiology at the University of Strathclyde in Glasgow. She has a strong interest in bioinformatics and is hoping to gain extra experience through her Summer Studentship, under the supervision of Dr Zahra Rattray and Dr Nicholas Rattray at the Strathclyde Institute of Pharmacy and Biomedical Sciences, that will help her progress to pursuing a PhD in the future.

Bioinformatics is a mix of biology, computer science, information engineering, mathematics, and statistics, and uses software and other tools to help store, analyse and understand complex biological data.

In her project: ‘Development of a gene expression bioinformatics pipeline to identify driver mutations of colorectal cancer,’ Lisa hopes to understand the key mutations driving colon cancer and any links they have to disease prognosis using existing clinical data from online freely available databases. The ultimate aim of which is to identify mutations occurring in patients with colorectal cancer and establish how they contribute to patient outcomes. This information may help inform understanding of colon cancer diagnosis, treatment, and prognosis.

Lisa explains: “In recent years, with significant advancements in gene sequencing technologies and the increasing numbers of biobanks from patient tumour biopsies, there has been a significant rise in the amount of clinical information available within the public domain. These datasets provide a significant wealth of information for researchers to examine patterns of gene expression and their role in disease. A key advantage of using these datasets is replacing the need for animal testing and refining their use in studying patterns of disease. If we can use information contained in patient samples, this will reduce the need for exploratory studies in animals which may ultimately prove to not translate to humans.”

• Marjorie Coote Animal Charity Trust 
• South Square Trust 
• The Barbara Welby Trust 
• Walker 597 Trust 
• The Toye Charitable Trust 
• Margaret Smith 
• Donald West 
• Luela Palmer 
• Eleanor Wexler 
• John Allen Brace 
• John Raddings 
• Smith & Nephew 
• Next 
• UBAEAV
• Johnson & Johnson 
• Boots 
• The Kennel Club 
• Avon 
• Bios Line 
• British Chemicals Association 
• University of Nottingham  

And all those who wish to remain anonymous