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Summaries of research

We signed the Concordat on Openness on Animal Research in the UK to show our commitment to help the public understand more about animal research.

We agreed to be clear about when, how and why we use animals in research. We aim to enhance our communications with the media and the public about our research using animals. We will be proactive in providing opportunities for the public to find out about this research.

Lay summaries

As part of this commitment we will provide lay summaries of research that involves animals for all new granted project licences:

2018

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.

2017

What animals are you planning to use? 

We will use mainly embryos and young animals from wild type and genetically altered (GA) mice.The GA animals are purchased from commercial suppliers or obtained through collaborations with other laboratories. We may generate some GA animals at Cardiff University.

For what purpose are the animals going to be used?

Our animals are part of different studies to help us understand how a particular brain region, the cerebral cortex, is formed during development. We want to gain insight into the four different processes that are necessary for the formation of the cerebral cortex, to better understand how alterations in these processes lead to brain disorders in infants or later in life. These four processes are: 1) neurogenesis, in which the neurons are generated by specific progenitors; 2) fate specification, a process by which neurons in the cortex acquire a particular identity that will determine their function and pattern of connectivity; 3) migration, a necessary step for the new born neurons to reach their final position within the cortex; and 4) circuit formation, when neurons identify their synaptic partners and establish contact with them.

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

The procedures that will be used are not expected to cause severe harm to the animals. Some of them will be humanely killed to obtain tissue for our research and some of them will receive an injection before that. Other animals will undergo surgery. This is conducted under anaesthesia, following aseptic technique to ensure the maximum level of safety, and always using analgesia (pain relief). We will also assess some behavioural characteristics of the animals by observing them in different settings.

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

As the cerebral cortex develops, it receives cells from different parts of the brain and signals from varied sources. These cells and signals influence the processes that are necessary for the cortex to form: the generation of neurons, their migration to their final position within the cortex and the contacts that they establish, with other neurons in the cortex or in other brain regions. Because of this complexity, it has not been possible yet to create an in vitro model to study cortical development in the lab. However, we also use cell culture when we study basic mechanisms that do not depend so much on the complex arrangement of cells and signals of the in vivo cortex.

What will be the expected benefits? 

The research proposed for this project comprises basic neurobiology but it could also eventually be relevant from a clinical point of view in the future. The expected results would translate into two potential benefits: - First, it will generate new knowledge about the function of several genes, involved in distinct processes during cortical development, contributing to our understanding of brain development and function. - Second, it will shed light on the pathophysiology of megalencephaly-polymicrogyria- polydactyly-hydrocephalus syndrome 3 (MPPH3), a human disorder caused by mutations in the CCND2 gene (one of the genes that we will study), and potentially of other disorders, providing information to affected families to help them understand the disease. A good understanding of the different molecules and processes involved in corticogenesis is also essential when new risks are identified that can severely affect the mental health of the population. An example is the current epidemic of Zika virus. This virus infects cortical progenitors very efficiently and has been linked to microcephaly, but new studies suggest that it might be causing further neurological problems that are only detected later in life.

What animals are you planning to use?

In the majority of cases we use adult wild-type mice. Only in rare cases of very specific and relevant scientific questions, we have the option to employ genetically altered mice. In these cases the genetic alteration is chosen based on previous scientific results and therefore respective mouse strains will not be created at Cardiff University but bought in from well trusted sources.

For what purpose are the animals going to be used?

Our animals are part of the overall strategy in the department to understand and to overcome mechanisms of therapy resistance in patients with highly malignant acute and chronic leukaemia. Therefore we model leukaemia in mice using techniques we have developed over many years.

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

All measures will be taken to reduce adverse effects experienced by the animals to a minimum. The worse expected adverse side effect is that the animals develop a picture of leukaemia which may reach a moderate level of severity. Otherwise all treatments and interventions will result in no more than transient discomfort and no lasting harm.

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

Experiments in animals are undertaken only based on clear evidence from relevant cell and tissue culture in the lab. Unfortunately, some principles such as clonal evolution or stem cell capacity can only be proved using live animals, because no alternative in vitromodels are available.

What will be the expected benefits?

Our findings will increase our knowledge of the mechanisms of why leukaemia develops and will have important implications for understanding mechanisms of resistance in leukaemia. Furthermore it will contribute to answer the question of why in some groups of leukaemia patients current therapies do not have the desired curative effects seen in other patients. The long term aim of this project is to create the basis for a future design of specific therapieswhich are more precisely adapted to the individual patient.

What animals are you planning to use? 

We will use mostly adult wild type and genetically-altered mice (not created in Cardiff).

For what purpose are the animals going to be used? 

Our studies aim to help understand: 1) how inflammation produced by the human body in response to viruses can be treated, 2) how cells of the immune system can be harnessed to improve infection control and 3) how the immune response can be manipulated to improve how the body reacts to virus-based vaccines.

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

To study viral infections requires us to infect mice with viruses such as influenza. Thus, animals used in these experiments will often be infected with viruses, causing mild illness and weight loss that will be monitored closely throughout infection. Pilot experiments are performed to ensure that the lowest possible virus dose (which thus induces the least disease) is used.

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

Wherever possible, studies are performed using cells in the laboratory that are infected with virus, or studying immune responses in blood of human volunteers.

What will be the expected benefits?

Findings from these studies will assist 1) the design of medicines to treat damage in the body that is triggered by viruses and 2) immunization strategies that use safe versions of viruses as part of the vaccine.

What animals are you planning to use? 

Wild type mice and rats and genetically altered mice generated externally.

For what purpose are the animals going to be used?

Our animals are part of a study to help us understand how the immune system contributes to the development and progression of inflammatory arthritis (e.g. rheumatoid arthritis).

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

Animals are injected with agents that cause arthritis with features similar to human disease. Animals are handled by trained and experienced researchers and are monitored closely for clinical signs of arthritis and indicators of wellbeing (e.g., appearance, behaviour and weight). To minimise suffering during injections, mice are anaesthetised and arthritic mice are handled on soft surfaces. Animals remain mobile and continue to feed and drink. Our genetically altered mice do not develop harmful characteristics.

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

Our animal studies are based on clinical observations generated using patient samples. This ensures our research addresses questions relevant to human disease. Our animal studies are supported by in silico and cell culture approaches that define mechanisms that promote arthritis progression. Animals are necessary to study the complex communication networks that occur between immune cells and joint tissues during arthritis.

What will be the expected benefits?

We aim to identify mechanisms that explain why patients develop inflammatory arthritis, and why some patients respond well to current drugs (e.g., anti-TNF) while others do not. By exploiting immunological mechanisms that underpin arthritis progression we aim to develop new drugs for patient treatment. Also, identifying biomarkers that can inform the best drugs for patients on an individual basis will aid a personalised approach to arthritis treatment.

What animals are you planning to use?

We will use wildtype and genetically altered mice and rats of all ages.

For what purpose are the animals going to be used?

Our animals are part of a series of studies that will help us to understand the structure and function of specialised brain cells, known as neurons, and the connections between them, called synapses, which allow the brain to process sensory information and are responsible for behaviours including attention and sleep. We use brain tissue harvested from humanely killed rodents to measure electrical activity and intracellular signalling mechanisms (calcium) in structures known as dendrites. Dendrites are the specialised structures on neurons that receive and interpret incoming chemical signals from other cells and their function is critical for the processing of information in the brain.  By gaining a better understanding of dendrites, neurons and circuits in the brain and how they regulate behaviour we can better understand how their disruption might lead to neurological disorders including schizophrenia, autism spectrum disorder and epilepsy. We work with animals that have been genetically modified to change the expression of specific genes that have been linked in human genetic studies to particular diseases. Using this approach we seek to identify the function of specific disease risk genes on neuronal and brain function and identify potential new targets for therapeutic manipulation.

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

Some animals in this project will undergo surgery to allow us to inject viruses into the brain that allow us to experimentally manipulate brain circuits. These surgeries are considered relatively minor procedures and are carried out under aseptic conditions by fully trained and competent individuals. All animals are provided with appropriate anaesthetic, antibiotic, anti-inflammatory and analgesic medications as required based on advice provided by a trained and licenced veterinary surgeon. Animals from which tissue is harvested for electrical recordings are humanely killed using an overdose of anaesthesia.

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

The complex circuitry of the brain limits the alternative options for studying particular aspects of the structure and function of its cells and circuits. However, alongside the animals used in the projects described we also use stem cell derived neurons which are taken from human volunteers and grown in cell culture and computational models.

What will be the expected benefits?

The work we are undertaking in this project aims to generate a new understanding of the function of key neurons and circuits in the brain and will provide a greater understanding of human genes linked to the human disease that produces the behavioural symptoms observed. By understanding how deficits in dendritic and synaptic function disrupt the function of neuronal networks we hope to be able to identify and test new target sites for therapeutic intervention using novel pharmacological or cell based therapies.

What animals are you planning to use?

Juvenile and adult rats and mice, some with spontaneous gene mutations.

For what purpose are the animals going to be used?

Our animals are part of a study to understand the mechanism underlying the expression of absence seizures in children and teenagers. These are non-convulsive seizures that consist of sudden, relatively brief lapses of consciousness accompanied by simultaneous activity of many neurons. These seizures are often accompanied by additional complications, including attention deficits, depression and anxiety that are not controlled by the drugs that block the seizures.

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

The procedures involve only minor and temporary distress to the animals, including brief surgery under full anaesthesia, injection of antibiotics and anti-inflammatory drugs and temporary removal from the home cage. All animals are provided with the appropriate pain relief.

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

Artificially kept cells and neurons, and computer programs that simulate the electrical activity of brain cells. None of them, unfortunately reproduce the connections among nerve cells that are characteristics of the intact nervous tissue. For this reason it is important to study the whole animal.

What will be the expected benefits?

Current medications, given as monotherapy, suppress absence seizures only in 50% of children and teenagers suffering from absence seizures. Our study should identify aberrant proteins that could be targeted for the development of novel drugs, in order to help children and teenagers with absence seizures.

2016

What animals are you planning to use?

Immunodeficient and immunocompetent in-bred strains of mice. Genetic alteration of mice will take place in a minority.

For what purpose are the animals going to be used?

Our animals will be part of a study to investigate the causes, and potential cures for metastatic cancer. A minority of the animals will be genetically altered to establish how specific mutations lead to cancer. The majority of mice will be transplanted with tumour cells in order to study how cancer cells grow and spread around the body, and to evaluate new therapeutic strategies to prevent metastasis, and to eliminate cancer cells.

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

Mice will develop tumours and these may spread to multiple organs. We monitor these animals daily for signs of stress and discomfort and if this cannot be controlled the animals are humanely killed. A proportion of the animals will carry tumours that can be readily scanned, which allows us to detect the tumours at their very earliest stages before the mice are likely to be adversely affected by the disease.

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

All of our studies are performed in cell culture where the majority of measurements and experiments are performed. Only when we are sure of the efficacy of a particular intervention or the function of a specific gene in cancer, do we confirm these findings in animal models. Hence the animal models are used sparingly as a final confirmation of our in vitro studies.

What will be the expected benefits?

These animal studies are the final step in either the identification of a new, previously undiscovered, mechanism of cancer, or in the development of a novel therapeutic intervention. Thus, this work directly contributes to the advancement of knowledge of cancer, and in the development of new anti-cancer agents for the clinic.

What animals are you planning to use?

The animals mainly used in this study will be mice. As we are studying brain development and behaviour, our animals will range from embryonic to adult. Some of these mice will be genetically altered to induce decreases or increases in the activity of certain genes. The animals used in this study are already in existence and will not be generated in Cardiff. We will also be using some rats in our studies of how the environment may moderate gene activity.

For what purpose are the animals going to be used?

Our genes encode a range of molecules that are essential for development and normal function. We know that in addition to what these genes encode, when they are active and how much product they produce, is also critical. Our animals are part of a study to understand the effects of changes in the levels of gene activity on how the brain develops and whether this results in altered behaviour. This process often goes wrong in neurodevelopmental disorders, and we want to model that. We also want to study how the environment experienced by a developing fetus in pregnancy can also affect gene activity and brain development.

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

The main harms may arise from how we perform the behavioural testing of the animals. However, we have considerable experience of behavioural experiments with rodents and have fine-tuned the tests to minimise any unnecessary stress and anxiety. This is in our interests as well as in the animal’s interests, as anxious or stressed animals produce poor behavioural data.

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

It is currently not possible to model the environment of pregnancy in a cell-based system. Nor is it possible to effectively examine behaviour other than in a living animal. However, where possible we will be using cell models to examine brain development.

What will be the expected benefits?

Our project will provide us with a better understanding of how brain and behaviour is affected by changes in gene activity, something that is a known risk factor in a number of neurodevelopmental disorders. Our research will also identify environmental factors, such as diet during pregnancy, that may alter gene activity and predispose the offspring to neurodevelopmental disorders.

What animals are you planning to use?

We will be using adult mice, mostly wildtype, but some also genetically altered. The genetically altered mice are obtained from other laboratories, and will not be generated at Cardiff University.

For what purpose are the animals going to be used?

We are conducting a study on brain cancer to understand why these cancers are so aggressive and to develop new therapies for patients. As part of the study, animal research will help us to better understand the interactions between cancer cells and normal cells surrounding them.

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

The animals will grow brain cancers, but as the brain has no pain receptors this process is in and of itself pain-free. In order to implant some of these cancers, some animals will undergo surgery, and we will use neurosurgical techniques, anaesthesia and medication (very much in the same way as neurosurgeons operate on human patients) to minimise any harm to the animals.

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

We have considered in vitro models of brain cancer, but these models cannot recapture the complexity of both the tumour and the normal cells surrounding it. It is becoming increasingly evident that the normal tissue around a cancer is not just sitting there, but both reacting to the cancer and also involuntarily contributing to its growth. Nevertheless, we always study brain cancer cells in the lab (in vitro) first before continuing our observations in an animal. We are also striving to improve currently existing in vitro systems by developing better models where cancer cells and normal cells are cultured together and we will use these systems to further refine our research.

What will be the expected benefits?

We expect to improve understanding of the biology of brain cancer, which will help in developing new and better therapies for patients. In the past, a large proportion of new drugs developed in the laboratory have failed to work in patients, and this is at least in part due to the fact that isolated cultures of cancer cells in vitro are not representative of the tumour inside a patient. Several types of brain cancer are currently incurable, and we expect that by studying the cancer in its appropriate environment – the brain – we will be able to identify new ways of how these cancers can be treated.

What animals are you planning to use?

We will use adult mice, some of which will be genetically modified. These mice will be obtained from other academic Institutions or commercial sources.

For what purpose are the animals going to be used?

The animals will be used to understand how the immune system recognises cancer and whether it can be boosted to recognise and kill cancer more effectively. During the study, animals will, for example, be given novel vaccinations to find out whether these can induce immune responses that are capable of destroying tumours. In other cases, they will be given new drugs to test whether these can help activate the immune system for the same purpose. Our findings have already shown us that in the case where strategies aimed at inducing immune responses work, they work only in a proportion of animals. With this in mind, we will also work out what the differences are between animals that respond to treatment (where the immune system kills the cancer) and those that do not (cancers carry on growing).

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

Animals will be handled and restrained in order to deliver e.g. vaccinations or drugs and for the purpose of monitoring tumour growth. Suffering is minimised by excellent handling techniques which limit contact time. There is strict adherence to tumour monitoring procedures which ensure that tumours cause no distress to the animal.

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

It is clear that the immune system can under some circumstances clear cancer but unfortunately, the precise details of those circumstances remain poorly understood. The immune system consists of a large number of different cell types which perform different functions in different parts of the body. This complexity cannot yet be recapitulated in the test tube therefore animal models remain necessary for examining the function of a fully integrated immune system. New methods however are being established and used to significantly limit the number of animals required to address key questions. We are developing the use of three dimensional organoid systems, which enable us to generate cancer in the lab instead of in animals. These well-characterised entities, can be implanted into animals, allow us to address questions relating to the immune system using fewer experimental mice. In addition, we use a variety of imaging systems to scan individual mice refining the accuracy of tumour measurements allowing conclusions to be drawn on smaller number of animals. Furthermore, use of these techniques will facilitate serial longitudinal analyses of tumour growth in individual mice, contributing significantly to reducing the number of animals required to achieve the study objectives.

What will be the expected benefits?

Our laboratory performs observational studies in patients with cancer and tests hypotheses arising from findings of these studies in preclinical mouse models. New information gained in this way is used to inform early phase trials in patients with cancer. We have a track record in this area thus the mouse to man pipeline is well established.

What animals are you planning to use?

The research uses adult rodents (rats and mice). While the overwhelming majority of rodents will be wildtype, in a few instances the rodents may be genetically altered to examine the impact of genes associated with and increased risk of disorders such as schizophrenia. These rodents will be imported to Cardiff University.

For what purpose are the animals going to be used?

Learning and memory depends on the interactions of multiple structures within the brain. The same structures that are thought to be vital for human memory are found within the rodent brain. We are seeking to understand how these structures are interconnected and how they make different, but related, contributions to memory. For this reason, the studies involve anatomical and behavioural techniques, the latter to examine different forms of memory. Starting with evidence from human amnesia, we can narrow down and identify the candidate structures that are necessary for different types of learning. Our interests are in how these structures co-operate normally and how these structures respond when one of them is damaged, as potentially happens in various clinical conditions. The focus is principally on structures within two brain regions, called the temporal lobe and the diencephalon.

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

To measure how brain regions normally interact during learning we can measure brain changes associated with forming memories. One example concerns the production of proteins by the brain that help to form and stabilise long-term memories. To identify the precise location of these proteins it is necessary to look at brain tissue after the rodent has been humanely killed. In other studies the goal is to determine whether a brain site is needed for a particular aspect of learning. Such studies involve temporarily or permanently disrupting that specific brain site. These studies often involve surgeries, which always occur under general anaesthesia. None of the sites targeted affect sensory or motor function. Because it is vital to assess learning by examining behaviour, it is critical that the animals do not have wider patterns of problems.

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

The research concerns the normal interactions of an incredibly complex system. An integral component concerns the ways in which different structures work with each other to produce behaviour that demonstrates learning. For these reasons, it is necessary to examine extensive arrays of brain systems. Non-invasive imaging techniques do not have sufficient resolution to identify the separate brain sites that make up the primary focus of this research (nuclei within the anterior thalamus). To limit the use of animals we have devised new, more sensitive behavioural tests. By examining patterns of gene expression associated with learning, we are able to look at the relative contributions of a multitude of brain sites in a single case, so maximising available information.

What will be the expected benefits?

Developing our understanding of areas of the brain that disturb memory in conditions such as Alzheimer’s disease. Research into the brain’s systems for memory has consistently focussed on a structure called the hippocampus. Our research has revealed the parallel importance of another site, the anterior thalamic nuclei. These same animal findings prompt non-invasive, imaging studies in humans, which seek to focus on these same regions and their interconnections.

What animals are you planning to use?

We will be using mice, some of which will be genetically modified to change their predisposition to cancer. We will import some strains of mice and also generate some strains at Cardiff.

For what purpose are the animals going to be used?

Our animals are part of a study to help us understand the basic mechanisms underlying cancer development and progression, to identify novel therapeutic targets and to help determine the usefulness of new anti-cancer therapies.

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

The adverse effects will be the development of cancers and the negative side effects of anti-cancer therapies. Our mice will be monitored for these adverse effects and humanely killed if multiple moderate adverse effects are seen.

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

We are increasingly using alternative models of cancer, most notably human tumours maintained in tissue culture. Whilst these cannot yet fully model tumour development in a whole organism, we are continuing to refine this approach such that it could ultimately replace our animal models.

What will be the expected benefits?

The knowledge we will derive will underpin future strategies for the development and use of novel anti-cancer therapies. This is particularly relevant to the treatment of cancer, as at present there are relatively few new options available in the clinic to modulate the course of disease. The majority of clinical benefits are likely to be long term; our principal hope is that by identifying candidate genes and candidate genetic pathways we will be able to refine and accelerate drug development for human therapy. There will also be short term benefits, primarily from the testing of novel drug therapies within our models. This latter approach has the potential to directly and immediately modify clinical practice.

What animals are you planning to use?

In our research we use South African clawed frogs (mainly Xenopus laevis and to a lesser degree Xenopus tropicalis) as they are the best model for developmental studies of this type.

For what purpose are the animals going to be used?

Our animals are used to provide embryos, which are required for our research on heart development.

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

To induce egg laying (and mating behaviour in males), injection of pregnancy hormone (chorionic gonadotrophin) is used, and this procedure can on rare occasions cause skin irritation or superficial wounds. The toads we use are exceptionally robust and fully recover from any such injury.

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

Mammalian pluripotent cells (embryonic and induced pluripotency state cells. ESC/iPSC) have a recognised translational potential for cardiac regenerative medicine and disease modelling in vitro. In order to realise this potential in full, it is necessary to improve our knowledge of how the heart and its components develop by studying heart development in vertebrate models such as Xenopus. We use both complementary models- mammalian ESC/iPSCs and Xenopus embryos in our research. As the knowledge of heart development improves, it leads to a gradual shift in use of in vitro models and concomitant reduction in reliance on in vivo models.

What will be the expected benefits?

The main benefit is in the form of improved understanding of heart development. Like most aspects of embryonic development, heart development is common to all vertebrates, and what we learn using Xenopus embryos is largely applicable to humans.

There are two main areas of potential applications of this kind of research: heart failure and congenital heart disease. Heart failure results in a loss of working heart muscle and the best treatment for it would consist of a timely replacement with new heart muscle. The main role of research on heart development here is to contribute to strategies for efficient generation of heart muscle tissue: if we learn how an embryo makes heart muscle, we might be able to apply that knowledge in a clinical setting. Congenital heart disease is the most common form of birth defects, with often poorly understood causes. Research into heart development can provide better insight into the underlying causes, and perhaps also offer strategies for development of new treatments.

What animals are you planning to use?

Adult wild type rats.

For what purpose are the animals going to be used?

Parkinson’s disease is a slow degenerative disease that affects over 120,000 people in the UK. The gradual death of a specific set of cells in the brain leads to slowness of movement, tremor and stiffness. Current treatment options are limited as the disease advances, and new therapies are being explored to repair the damage caused to the brain by using altered viruses or cells implanted in to the brain. In order to assess the safety and efficacy of these new approaches we need a good representation of the disease in an animal model. This project will involve animals as models of Parkinson’s disease and attempt to recreate these models as close to the patient situation as possible to test these new therapies.

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

The majority will undergo 2 short surgical procedures, firstly to produce the Parkinson’s disease on one side of the brain and secondly to repair the damage. They may be anaesthetised for brain imaging studies but the process of using these studies reduces the number of animals that are needed overall. The rats are given pain relief after surgery and are monitored closely throughout the experiments. Parkinson’s patients receive daily medications and the same is replicated for short periods of time in the rats. This is delivered typically by injection and the place of injection is changed daily to ensure that the animals do not become sore.

What alternatives did you consider before embarking on the use of animals in your research?There are no real alternatives to this type of research. The very nature of the research is that we are trying to replicate, as close as physically possible, the environment in which a new therapy might be trialled in patients so that we may anticipate or prevent any potential problems. To do this we need a whole system, and a cell culture cannot reproduce this.

What will be the expected benefits?

The overarching aim of this work is to optimise new treatments for Parkinson’s disease and ensure that these new therapies are safe and compatible with a patients’ existing medications.

What animals are you planning to use?

We will use mice, both juvenile and adult. The majority will be genetically altered, bred from imported lines.

For what purpose are the animals going to be used?

The animals are part of a study to help us understand how the visual areas of the brain adapt to visual experience made during childhood, why this can sometimes lead to vision disorders such as lazy eye, and how different brain areas work together to produce visual perception.

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

We have considered in vitro (‘in the dish’) which can be useful in elucidating certain cellular aspects of brain function but it is impossible to maintain a whole brain and eyes alive in isolation in order to truly test brain function, let alone behaviour.

We are using computer-based modelling which has helped us in the past to interpret results obtained in vivo, but data collected from animals are needed to feed into any models to ensure they have a sound basis.

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

Animals will be subject to high-resolution brain imaging for which they need to be prepared surgically under general anaesthesia. There is a risk of post-operative pain as well as of infection; these will be minimised by treatment with analgesics, antibiotics and anti-inflammatories as appropriate.

What will be the expected benefits?

We hope to find out, at the level of individual cells and molecules, how we learn to see and what goes wrong in conditions such as lazy eye but also in neurological disorders (such as autism or schizophrenia) that can affect sensory systems. If we discover the mechanisms leading to those disorders then we will have a better chance of developing new methods of treatment.

What animals are you planning to use?

We will use young and adult mice that are both wildtype and genetically altered. The mice are already genetically modified and none will be performed at Cardiff University.

For what purpose are the animals going to be used?

The animals are part of a study to help us understand why people get type 1 diabetes. In addition, the mice, like humans, get diabetes very similar to the human disease, if they are not treated. They will be involved in research to find ways of preventing and curing diabetes.

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

Most of the animals will not experience any harmful effects. Some animals may experience minor discomfort for a few seconds when an injection is given. Some animals will develop diabetes, where they will become thirsty and pass more urine. They may start to lose weight. We will either treat them with insulin to control the diabetes, or they will be humanely killed before they have significant illness or weight loss.

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

The diabetes studies will be combined with tests in cell culture and where possible, the research will be done in cell culture

What will be the expected benefits?

Benefits from this project include better understanding of the development of type 1 diabetes as the model that we use has some very similar features to the human disease. The mice will be involved in research to prevent and cure diabetes using a number of different strategies. If these are successful, the aim is to take this in the next steps towards applying these strategies to human diabetes.

What animals are you planning to use?

We will use mainly embryos and young animals from wild type and genetically altered or GA mice. The GA animals are purchased from commercial suppliers or obtained through collaborations with other laboratories.

For what purpose are the animals going to be used?

Our animals are part of a study to help us understand how a specific type of proteins, called delta protocadherins, contribute to the development of the cerebral cortex. These proteins are located on the membrane of the cells to help them recognize other cells and interact with them. One of the delta protocadherins is mutated in a human disorder called Juberg-Hellman Syndrome, in which very young girls develop epilepsy and other neurological symptoms. Why this happens is currently unknown, and our animals will help us to investigate what goes wrong in the brain of these girls and develop targeted therapies to help them.

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

The procedures that will be used are not expected to cause more than temporary discomfort to the animals. Many of them will be humanely killed to obtain tissue for our research and some of them will receive an injection before that. Other animals will undergo surgery. This is conducted under anaesthesia, following aseptic technique to ensure the maximum level of safety, and always using analgesia.

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

As the cerebral cortex develops, it receives cells from different parts of the brain and signals from varied sources. These cells and signals influence the processes that are necessary for the cortex to form: the generation of neurons, their migration to their final position within the cortex and the contacts that they establish, with other neurons in the cortex or in other brain regions. Because of this complexity, it has not been possible yet to create an in vitro model to study cortical development. However, we also use cell culture when we study basic mechanisms that do not depend so much on the complex arrangement of cells and signals of the in vivo cortex.

What will be the expected benefits?

Our research will generate new knowledge about the function of the delta-protocadherins during cortical development, contributing to our understanding of brain development and function. This is a very important field, considering the heavy burden that psychiatric and neurological diseases pose not only on society, but also on the health systems of many countries. In addition, we expect to shed light on the pathophysiology of Juberg-Hellman syndrome. We will then be able to provide information to affected families to help them understand the disease, but also to clinicians, to guide them in the development of new treatments.

What animals are you planning to use?

Adult wild type rats.

For what purpose are the animals going to be used?

Our animals will be used in a study to determine the changes that occur in the retina in glaucoma. Glaucoma remains one of the commonest causes of vision loss in which the retinal cells that send light signals to the brain die, resulting in loss of vision. We will undertake research to see if it is possible to enhance the remodelling and healing responses of these cells to recover vision that has been lost in glaucoma. If successful, our work will, for the first time, lead to clinical treatments to recover some of the vision that has been lost in this disease. Our work is essential for the design of clinical trials to reverse vision loss in glaucoma patients.

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

We did consider the use of culture systems run at elevated pressures since this can simulate some of the direct pressure effects on neuronal tissue. However we rejected this since it does not emulate the appropriate neuroglial/ immunological changes that occur in vivo in glaucoma.

We also considered using the mouse as a glaucoma model but decided against it as the mouse eye is small and difficult to assess in vivo and the rat will provide a much better and robust inducible model of glaucoma.

We do use an in vitro model of retinal ganglion cell degeneration based on the retinal explant. This is ideal for studying the effect of therapeutic agents and for determining any adverse interactions between agents. The explant model is based on retina harvested from animals which have been humanely killed.

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

The harm level is mild since all procedures are conducted under general anaesthetic. As part of our research we generate chronic experimental glaucoma in rats, but just as in humans, this does not cause any discomfort related to the eye.

What will be the expected benefits?

Our experiments will provide a proof of concept that it is possible to remodel and rewire the retina to reverse the loss of vision in glaucoma. We do not expect to achieve total reversal but partial recovery would still be clinically significant and a great benefit for patients. We hope that treatment for glaucoma will be a single injection into an eye, to allow the parts of the retina that have degenerated to recover and regrow. The therapeutic agent that we will use is already in clinical trial for the recovery of function in spinal cord damage so we are optimistic that our experiments will form the basis for the design of clinical studies.

What animals are you planning to use?

We are planning on using 10-12 week old adult mice, both wild type and mice that are genetically altered (GA) so they are unable to make lipid (fat) processing enzymes. These GA strains are currently bred in Cardiff University.

For what purpose are the animals going to be used?

Our animals are part of a study to understand the role of specific lipids (fats) that are found in the skin during repair. These fats are made by immune cells that travel to the site of a wound after an injury. The role played by these fats at the site of a wound is unknown and we are keen to study if the presence of these fats changes how a wound heals.

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

A small punch biopsy will be made to the back of the mice. The wounds will heal within one week and cause little irritation to the mouse. The mice will be monitored continually following biopsy to ensure they suffer no adverse effects as a consequence and pain relief will be administered when necessary.

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

Within this project we are using a cell culture model. We will make the same small biopsy in this model and add lipids of interest and study the wound repair. However, a drawback of this model is firstly that immune cells, that generate the lipids of interest, are not present, and secondly it is not possible to genetically alter skin cells used in this approach.

What will be the expected benefits?

The primary expected benefit of this research is to assist us in designing possible wound therapies to change the levels of these lipids in human and animal wounds to speed up recovery times. If we find that these lipids aid skin wound recovery we can develop formulations to add into wounds to increase their levels at the site of action. Alternatively if we find they slow healing in any way, we can develop formulations to inhibit their production.

2015

What animals are we planning to use?

Approximately 90% of the animals used will be wildtype adult rats, the remainder will be genetically altered adult mice (and wildtype controls) from existing strains (i.e. no new genetic alterations will be made).

For what purpose are the animals going to be used?

This project has three main objectives:

  • To understand the psychological and biological mechanisms involved in normal emotional and cognitive processes.
  • To examine how and why these processes fail in rodent models of psychological disorders.
  • To examine how common laboratory techniques (such as injections) impact on laboratory animal welfare and to explore ways in which to minimise these effects.

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

The procedures used here are not expected to produce severe adverse effects. The key behavioural observations involve the detailed examination of animals' responses to foods. That said, some of the procedures will be directly aversive (e.g. producing short term stress or nausea). We will use the minimum level of any aversive technique that is consistent with the goals of the study. Some animals will undergo surgery under anaesthesia. Here we will follow veterinary advice to perform these techniques in the safest possible manner and always using analgesia.

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

Emotion and cognition are only seen in whole organisms. To investigate both normal function, and its disruptions, requires animals because alternative models (such as those based on cell cultures or computational methods) cannot yet capture the complexity of brain circuits. That said, this project is paralleled by research in humans and so only scientific goals that cannot be achieved through research with human participants are included.

What will be the expected benefits?

Psychiatric disorders are a major health burden in the UK (and worldwide). One bottleneck in developing novel treatments is a lack of targets for drug discovery. This project will develop the understanding of emotion and cognitive function in rodents, and how these fail in rodent models of psychiatric disorders. Such outputs will aid the drug development process by identifying targets for new therapeutic techniques.

Many thousands of rodents are used annually in laboratory work based involving techniques such as injections. The welfare impact of these techniques has received little direct scientific investigation, meaning the aversive impacts, and means to minimise them, are not known. This project will provide information about how aversive some common techniques are and about ways to minimise or avoid that harm.

What animals are you planning to use?

Mouse, juvenile and adult, from established genetically modified lines.

For what purpose are the animals going to be used?

Our animals are part of a study to help us understand how retinal cell loss results from inherited defects in mitochondrial genes  and if there are any ways of preventing this.

Inherited optic nerve atrophy (or optic neuropathy) is one of the commonest causes of human irreversible visual loss in the UK. There are currently no medical or surgical treatments available. The diseases lead to visual loss through the disruption in retinal ganglion cell function or loss of these cells. Genes that control the shape and configuration of organelles called mitochondria, which are present in each cell of the body, have been found to be mutated in patients with inherited optic atrophy.

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

The mutation of eye disease genes in mice creates minimal suffering, since mice are nocturnal animals with excellent senses other than vision, and they do not rely on good vision to find food or water. The treatments to be used will mostly be agents with prior published safety data, so that doses and toxicity are likely to be avoidable or minimal. The adverse effects could include ocular discomfort and inflammation in the eye. Mice will be monitored and will be withdrawn from any treatment if they display harm.

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

Investigating the complex processes involved in inherited optic neuropathy, which consists of many different cellular and tissue interactions in the retina and optic nerve, requires animals to establish the outcome of these processes. Animals have to be used because it is not possible to remove tissue from the eyes of living patients who may be tested with new therapeutic agents without any data on their effectives.

What will be the expected benefits?

This project will translate directly to the benefit of people. The research will assist us in finding new treatments and will be of benefit to those with genetic forms of visual loss.

What animals are you planning to use?

For studies that require the use of animals, we will use mouse models only. The majority of studies will utilise inbred mouse strains that are not genetically altered. For some studies where we wish to evaluate the accumulation of virus within a tumour grown in a mouse, we will use mice genetically engineered to have a defective immune system, as this is the only way that human tumour cells can be grown in these animals. For all studies mice will be bought in from commercial suppliers and used at between 8-14 weeks of age.

For what purpose are the animals going to be used?

Our research pioneers the use of a type of virus called adenovirus, which in humans causes mild, non-life threatening infections of the respiratory and GI tracts, as novel therapies for cancer. By removing the disease causing genes, and replacing them with therapeutic genes, we can effectively treat cancer cells in the lab (in vitro). However, treating cancer in animals is hugely more complex compared to in vitro models, as the virus interacts with multiple "off target" proteins and cell types that can cause toxicity and results in accumulation of virus in non-target cell. Our animal studies will therefore help us to understand how the virus interacts with proteins and cells in the whole animal, allowing us to refine and tailor the virus so it selectively accumulates within only the cancer cells.

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

The mice will be housed together in social groups. For our studies, we will inject the mice with virus and monitor (non-invasively, using bioimaging techniques) which organs the virus accumulates in. It is therefore anticipated that the animals will not experience any significant discomfort over the course of the experiment. At the end of the experiment, we will ensure all possible organs are retained for analysis, therefore reducing the total number of procedures required.

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

Before commencing any studies in animals, we perform extensive studies in vitro using cancer cell lines in order to ensure we are only performing animal studies with our lead candidate viruses. Although there are no systems that replace whole animal models, our laboratory is pioneering the use of clinical cancer samples isolated directly from patients, through agreement with Wales Cancer Bank, and access to these valuable samples form an extremely valuable addition to our in vivo studies.

What will be the expected benefits?

Our studies seek to develop viruses that can, once introduce into the blood stream, "seek out and destroy" tumours through selective replication of the virus within the tumour, and/or through the expression of a protein within the tumour that will promote killing of the cancer cell.  This is thus a highly translational project, that we hope ultimately will result in significant clinical benefit to cancer patients, especially in those patients who present with chemotherapy resistant disease.

What animals are you planning to use?

We are planning to use juvenile and adult mice from both wild-type and genetically altered animals. The GA animals are purchased from commercial suppliers and acquired through academic collaborations.

For what purpose are the animals going to be used?

Our animals are part of a study to understand the molecular and cellular basis of social behaviour in pathological and non-pathological conditions. In this context we are particularly interested in Autism Spectrum Disorders (ASD), as they are associated with defects in social behaviour. Animal models of ASD help us to gain access to the molecular and cellular mechanisms responsible for the social deficits observed in the disorder, a type of study almost impossible to achieve in humans.

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

During the course of this project the animals will go through various behavioural tests, with a particular focus on the social behaviour. The potential harm that could be done to our animals in this project is an elevation of stress. But sociability is a natural behaviour which can be highly influenced by the stress level. To avoid a rise in stress levels we conduct the different social behaviour tests in the least stressful environment possible (e.g. low light level to no light, quiet room, automated measurements to avoid people in the room). Too many tests could also add to the stress on the animals so we limit the number of tests on any single animal to minimise this.

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

Understanding the relationship between behaviour and specific cellular and molecular mechanisms necessitates the use of living animals. Nonetheless, before asking questions in vivo we perform in vitro experiments, in particular on neuronal cultures derived from embryonic stem cell lines, where we are able to precisely dissect these specific molecular and cellular mechanisms. This allows us to better understand the results we obtain from our in vivo work and therefore minimize our use of animals.

What will be the expected benefits?

Autism Spectrum Disorders are frequent in the population (about 1% of the western population is diagnosed for autism) and to date no curative treatment exists. The main limitation in the development of therapeutic treatment is our limited understanding of the precise biological mechanisms underpinning the disorders. The knowledge we will develop during this project is precious because it will help unravel potential new targets for the development of therapeutic strategies for ASD, but also for social behaviour deficits in general.

(Differentiated cell culture as an alternative to animals in metabolic studies)

What animals are you planning to use?

Adult rats (only a small number required since each gives several hundreds of millions of the required cells).

For what purpose are the animals going to be used?

Cell culture has both ethical and economic advantages over whole animal work. For cells to be used as effectively as possible their properties in the culture dish need to be as close as possible to how they are within live animals. However, specialised cells that maintain organ specific properties in culture do not freeze well.  This project is dedicated to finding so alternative methods of cell preservation. Different types of cells can then be used in the lab for all manner of research.

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

Enzyme inducers are used to raise the number of cells needed and the lowest levels that are effective will be used. Cells are removed under terminal anaesthesia.

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

With ethical approval, human cells are being prepared and preserved. However, the human tissue varies greatly in quality. This is due to the time after which it becomes available, the age of the patient, life style choices and medication. This means that cell preservation methods are often compromised due to the quality of the starting cells. For this reason we need to use animals to produce the high quality of cells needed.

What will be the expected benefits?

If cell culture is optimised, this should enable the use human cells to replace animals, partly, in the development of medicines. This type of work can reduce animal experiments, facilitate cell transplantation as an alternative to organ transplantation and may be applicable to the preservation of human organs.