Examples of BBSRC-funded animal research
BBSRC funds animal research in a range of research areas from fundamental research which seeks to understand how organisms work and which could eventually contribute to improving human or animal health, to applied work that is aimed at treating animal diseases or improving animal welfare.
A 'heavy' mouse contributes to the 3Rs
"BBSRC-funded research has led to the creation of a 'heavy' mouse, the world's first animal enriched with 'heavy' molecules so that the structure of the animals' tissue can be seen in unprecedented detail. This allows researchers to analyse the tissues in ways they can't do with natural samples.
It is expected that the 'heavy' tissues could help the development of lab-grown tissue that could be used to replace heart valves, could lead to improved success rates for medical implants and reduce the need for animals in research, as well as opening up an entirely new approach for biochemical investigation (it has already led to new knowledge about the role of a protein called poly(ADPribose)).
The heavy mice are created by letting the mouse eat as much as it likes of mouse feed rich in carbon-13 - a type of carbon that slightly heavier than most carbon in the environment. The different diet doesn't harm the mice, but does allow researchers to see the atomic structure of its tissues. This in turn helps them to grow tissues in the lab that look identical to those grown in a mouse. These tissues are less likely to be rejected if they were to be implanted, and provide a more accurate in vitro model of the mouse than has been available before so that fewer experiments need to be done in vivo."
From research with fish to patient benefits
"Professor Russell Foster's work illustrates how underpinning research in fish can be translated to mice and ultimately used to benefit humans. He won a BBSRC Innovator of the Year prize in 2012 for this work and was awarded a CBE in 2015 for services to science.
Our understanding of the eye was thought to be largely complete; the rod and cone cells detect light, some processing is done by inner retinal cells and the information passes into the brain. However, working with fish Professor Foster's team discovered that the eye contains another light sensitive cell; they found a new photoreceptor gene that was not expressed within the rods and cones but within inner retinal cells. He then showed that mice also have this "third photoreceptor". Genetically engineered mice which lacked rods and cones, still showed responses to light, including the regulation of 24-hour body clocks, sleep, alertness, mood and even pupil size. These new cells are called "photosensitive retinal ganglion cells", pRGCs. By collaborating with ophthalmologists in London and Oxford, he then showed that humans also have pRCGs.
This discovery is changing our understanding of clinical blindness. Individuals who have lost their rods and cones, but have intact pRGCs, are not completely blind. They are unaware of light, but should try to expose themselves to sufficient day-time light to regulate their body clock. Professor Foster is looking at whether it is possible to use the fundamental knowledge of how pRCGs work to develop new drugs that would be useful to those who have lost their eyes completely or who have damaged pRGCs.
The discovery is also changing the way architects and lighting engineers think about lighting in buildings. The pRGCs are most sensitive to blue light, and so enriching artificial light with blue light, or opening up internal spaces to natural light, can optimise human performance at home and in the workplace."
Slipped discs in dogs
Researchers at the Royal Veterinary College have been working to improve the welfare of dog breeds at greater risk of a type of slipped disc in their spines.
They performed a study of 700 dogs which showed that breeds with a 'long and low' body type - long backs and short legs, such as miniature Dachshunds - put them at a greater risk of the painful and debilitating condition.
The researchers examined 700 dogs of diverse breeds referred to the RVC's Queen Mother Hospital for Animals over the course of a year, of which 79 dogs suffered the relevant type of slipped disc. The dogs were weighed and measured and the results subjected to statistical analysis. Having a longer and lower body shape was the biggest risk factor, but small body size and being overweight also made dogs more vulnerable.
Since publishing the paper the researchers have been working with the Dachshund Breed Council to translate the findings into practical advice for Dachshund breeders and owners. The council has published a lay summary of the study on its website, and invited one of the researchers to speak at a recent event.
PMWS in pig herds
Post Weaning Multisystemic Wasting Syndrome (PMWS) is a very common disease in pigs which causes a wide range of unpleasant symptoms and is fatal in around 30% of cases. It costs farmers millions of pounds in efforts to control it.
Scientists from the Royal Veterinary College wanted to know more about how the infection was able to spread without being attacked by the pig's immune system.
Six healthy pigs were humanely euthanised at six-months-old and immune system cells were sampled from the lungs, blood and bone marrow.
Experiments demonstrated PMWS can infect the immune cells and thus avoid detection by the immune system.
The work improved our understanding of how PMWS works, and offered new avenues of research to work towards better prevention and new treatments.
In addition, the scientists discovered in subsequent studies that virus replication was aided by any kind of stress, meaning that management as well as an in general stress-free environment may aid the clearance of the virus.
Improving the health and wellbeing of livestock
Studies on livestock have a vital role to play in improving the health and wellbeing of farmed animals. Calves are usually reared on 'least cost' principles which have been described by some as maintaining the animal in a 'state of chronic hunger'. This method can seriously impact calf health, with human studies suggesting that underfeeding newborn babies is a major risk factor for metabolic disease in later life.
In the study, the researchers administered a measured dose of glucose and insulin intravenously into calves at various ages. They then took blood samples over a few hours to measure insulin sensitivity and glucose responses. By analysing the blood of dairy calves with restricted access to milk versus those with unlimited access, scientists have uncovered that unlimited access improves the health, welfare and productivity of dairy cows. The research, developed in partnership with industry will go on to inform farming practices, to ensure the highest level of welfare is maintained.
Mice to understand the mechanics of maternal nutrition
The B vitamin folate is very important for the growth and development of a healthy foetus. Being deprived of folate and other nutrients can have lifelong consequences for health and, for example, can increase chances of obesity, cardiovascular disease and type 2 diabetes.
By looking at folate supply in mice, researchers at Newcastle University have discovered that mice born to mothers with a low folate supply during pregnancy and lactation were at higher risk of metabolic disease as adults. It appears that the mouse tissues 'remember' their previous nutritional state.
In particular, mice whose mothers had low folate intake were more susceptible to the adverse effects of a high fat diet and had higher than expected concentrations of fats in their bloodstream when they became adults. This suggests that an adequate supply of maternal folate may be important in enabling offspring to handle higher fat diets eaten by many people.
In addition, the Newcastle researchers discovered that the low folate supply during early life changed DNA markers and therefore gene expression. By looking at tissue samples derived from mice that were humanely euthanized, they discovered that epigenetics plays a part in this memory as mice with inadequate folate supply had altered patterns of DNA methylation which turns genes on and off.