Summaries of 2018 research

What animals are you planning to use?

Adult male and female mice, wild type or genetically modified will take part. Genetic modifications will not be done in Cardiff University, genetically modified animals will be obtained from a commercial supplier.

For what purpose are the animals going to be used?

Our animals will be part of a study that aims to better understand chronic inflammation in patients who have kidney failure and to help develop treatments to reduce this inflammation and limit its negative impact on patients’ health.

What will be the harms to those animals and how will these be limited?

To mimic the low grade inflammation that is observed in patients with kidney failure, animals will need to be repeatedly given substances that will induce low inflammation. Administration will be done by injection, either in the peritoneal cavity or intravenously, which will only induce a short lasting, mild discomfort to the animals.

To limit this discomfort, injections will only be performed by experienced staff and will only be repeated a limited, carefully determined, number of times. At the end of the experiment, animals will be humanely killed in order to obtain the tissues and samples necessary to our study.

What alternatives did you consider before embarking on the use of animals in your research?

Our work also includes experiments in the lab , for example using samples from patients, to mimic chronic inflammation and study it.  Unfortunately, inflammation is a very complex process that is impossible to fully reproduce in a test tube, which is why animals need to be involved in this study.

What will be the expected benefits?

The involvement of animals in this project will help to better understand and better manage chronic inflammation and its associated complications in patients with severe kidney dysfunction.

What animals are you planning to use?

Rats and mice of various ages will be used. Some of the mice will be from established genetically altered lines.

For what purpose are the animals going to be used?

The majority of the animals will be used in a range of project licences involved in medical research at Cardiff. Animals will be bred and maintained for use on these projects. We also have highly trained technical specialists who have the ability to create novel genetically altered (GA) rodent models, cryopreserve embryos and sperm from GA animals and reconstitute GA lines when required.

What will be the harms to those animals and how will these be limited?

The largest proportion of animals accounted for under this project will be produced by natural breeding techniques and are likely to only experience mild effects. The animals that show adverse effects will be closely monitored for health and welfare issues.

The establishment of new models of human disease involves surgical procedures. Possible adverse effects may include wound infection or an adverse reaction to anaesthesia. These will be minimised by using aseptic surgical techniques, analgesia and post-operative care. After establishing these new models, the animals will be provided to the relevant research group for further study within the scope of other project licences.

What alternatives did you consider before embarking on the use of animals in your research?

As there are no non-animal alternatives, the use of the rodent model is needed in order to breed strains which model human diseases in order to help develop new novel therapeutics for the treatment of such diseases. Many of the research projects will involve the use of in-vitro systems such as cell culture, human tissue assays, computer modelling to complement the animal work. However, the justification for using animals lies with the end users’ project licence having been subject to ethical, peer and Home Office approval before being granted.

What will be the expected benefits?

Genetically altered animals are an invaluable tool for understanding disease processes in man and animals and for the developing treatments and therapies for them. Several approaches exist to produce new GA models for disease research. These mainly rely on the ability to manipulate embryos at an early stage of development and then successfully produce offspring from those manipulated offspring. We can provide the skills, knowledge and specialist equipment required to efficiently produce animals carrying specific genetic alterations with minimum animal wastage. Archiving of GA lines as frozen embryos and/or sperm from modified lines not only helps reduce animal use by minimising the number of GA lines maintained on the shelf, but also facilitates the sharing of GA lines between researchers, providing further opportunities for reduction. Repositories will be available for future use to safe guard against the potential loss of a line which would be difficult to replace.

What animals are you planning to use?

We will use rodents, specifically rats and mice. We will use juvenile and adult animals.

For what purpose are the animals going to be used?

Our animals are part of a study to help us understand the effects of risk factors for brain disorders, especially psychiatric disorders. This work includes behavioural, molecular and physiological studies.

What will be the harms to those animals and how will these be limited?

Most of the animals will partake in behavioural studies with relatively low risks of harm. A small number of animals will receive MRI scanning of the brain under anaesthesia or undergo surgery under anaesthesia. A small number of animals will receive drug treatments aimed at understanding and better treating brain disorders.

What alternatives did you consider before embarking on the use of animals in your research?

Our work with animals forms part of an integrated research programme investigating neuro-psychiatric disorders. In this programme we take direct measurements from patients and also conduct research with neuronal cell samples derived from patient tissue. Wherever possible we minimise the use of animal models for our research, but they do form an important part of our overall programme.

What will be the expected benefits?

Our work will help to pave the way for the development of a new understanding of mental disorders based on biology. Advances in biological understanding of risk for mental disorders will take us beyond current understanding and classification of psychiatric disorders and, we anticipate, will lead to the development of new approaches for the treatment of these disabling conditions.

What animals are you planning to use?

We use mice and rats to study neurodegenerative diseases. We use wildtype and genetically altered rodents, which are either generated at Cardiff University, or created and purchased from licenced suppliers. We also use neurotoxins to develop our models of neurodegeneration in wildtype rodents.

For what purpose are the animals going to be used?

Our animals are part of a study to help us understand why neurodegenerative diseases occur and to develop treatments for these diseases. We predominately focus on Parkinson’s disease, Huntington’s disease and Alzheimer’s disease. We are creating new cell and gene therapies and we are studying the impact of these treatments on motor and non-motor impairments. Our aim is to repair the degenerative brain and to slow or stop the progression of these conditions.

What will be the harms to those animals and how will these be limited?

The animals could be genetically modified or exposed to neurotoxins to create the neurodegenerative diseases. Cell and gene therapies require surgical implantation and testing of new drugs or therapies often requires needle injections. The welfare of the animals is of the utmost importance. Therefore, all animals are monitored very closely for weight or health changes. Surgical interventions are conducted under anaesthetic, with additional analgesics, in a sterile environment. Rodents will only ever be exposed to a limited number of procedures. All welfare checks are carried out by the researcher, with additional support from animal house staff and the named veterinarian.

What alternatives did you consider before embarking on the use of animals in your research?

We also use cell culture models to explore these neurodegenerative conditions and to develop the early phase therapies. However, prior to translation to the clinic it is necessary to test these therapies in rodent models to ensure sufficient safety and efficacy.

What will be the expected benefits?

This research should ultimately benefit people with neurodegenerative diseases such as Parkinson’s disease, Huntington’s disease and Alzheimer’s disease by offering new opportunities to slow or stop the progression of these debilitating diseases.

What animals are you planning to use?

Adult and juvenile (3 week old), normal and genetically altered (GA) mice. GA mice will either be bred in Cardiff, supplied by collaborating scientists or recognised commercial suppliers. Normal mice will be supplied by recognised suppliers.

For what purpose are the animals going to be used?

Our animals are part of a study to help us understand the fundamental reasons why different cancers arising in the breast appear different to each other. We will also try and understand why different genetic mutations cause some types of cancer but not others e.g. why do people who inherit a mutation in the BRCA1 gene tend to get breast and ovarian cancer but not liver or skin cancer, as BRCA1 is a gene important for protecting all cells from damage. Finally, we will build on our previous studies to research treatments aimed at treating the different types of cancer and understanding resistance to such treatments.

What will be the harms to those animals and how will these be limited?

Some mice will undergo surgery under general anaesthetic for implantation of cancer material. Others will develop breast cancers spontaneously. Breast cancers, being located close to the body surface, have minimal health effects but if they get large or are close to the legs they may affect walking. Some animals may receive treatments for these cancers which could cause side-effects. We will have a ‘welfare score’ system to assess the overall health of all animals carrying cancers as well as a number of absolute defined limits beyond which adverse effects will not be allowed to proceed. When the ‘welfare score’ reaches the prescribed limit the mouse will be humanely killed.

What alternatives did you consider before embarking on the use of animals in your research?

Our project relies heavily on approaches which do not involve the use of animals. For example, having identified possible reasons for differences between cancers, or why some genetic changes cause some types of cancer but not others, we can often understand these reasons in much more detail using experiments on cells grown in the laboratory. We can also see whether possible treatments are likely to be effective by first using cells in dishes. We have already had a great deal of success using these approaches. However, the final research on any idea about the origins of cancer must be done under conditions which copy as closely as possible the human body. This means using an animal which has a blood circulation, immune system, etc. We will continue to use cells grown in dishes for many of our studies but we have also reached the point in some studies where we have done as much as we can in the dish and must now test our ideas in an animal.

What will be the expected benefits?

If we can understand the fundamental reasons for the differences between cancers, we can identify potential targets for treatment specific to different cancer types and begin to develop treatments for them. This could lead to ‘personalised cancer medicine’ for patients. We have already identified one such potential target previously and are beginning to develop possible therapies against it. These will need to be researched in cells in dishes and, if they prove effective, in animal studies. Understanding why different genetic mutations cause some type of cancer but not others will advance our fundamental understanding of the biology of cancer and also may lead to new therapeutic approaches if we can mimic the features that protect one tissue from cancer in another tissue that is sensitive.

What animals are you planning to use?

We are using genetically altered mice that were purchased as embryos from commercial suppliers.

For what purpose are the animals going to be used?

These genetically altered mice will be involved in studies to understand how eye injuries can be treated by stem cells, and to learn how different genes regulate stem cell behaviour.

What will be the harms to those animals and how will these be limited?

Stem cells will be removed from the front of the eye to mimic age-related disease or trauma in humans. This study is performed in a strain of albino mice with retina blindness by weaning age, therefore no decrease is expected in the animal’s visual capabilities caused by this study.

What alternatives did you consider before embarking on the use of animals in your research?

These genetically altered mice are the only available model to identify and isolate slow-dividing stem cells as there are no current alternatives to purifying adult stem cells based on their in vivo division rate, such as human cells in vitro or simpler organisms which have very short life spans.

What will be the expected benefits?

From this project, we aim to develop a new animal model of blindness that more closely mimics human age-related disease and trauma, by specifically targeting stem cells. A major objective is to reveal the genes specifically expressed in the stem cells that can be used as therapeutic targets and new stem cell markers, which we aim to achieve by isolating these stem cells based on their slow-cycle rate.