News from the School

The European Research Council (ERC) has announced today the award of 255 Advanced Grants to outstanding research leaders across Europe, as part of the EU’s Horizon Europe programme. Four University of Cambridge researchers are amongst those to receive this prestigious and competitive funding.

The University of Cambridge’s grant awardees are:

Dr Albert Guillén i Fàbregas in the Department of Engineering for his project Scaling and Concentration Laws in Information Theory.

Fàbregas, who has previously received ERC Starting, Consolidator and Proof of Concept Grants, said: “I am truly delighted with the news that the ERC will continue to fund my research in information theory, which studies the mathematical aspects of data transmission and data compression.

“This project will broaden the theory to study arbitrary scaling laws of the number of messages to transmit or compress."

Professor Beverley Glover in the Department of Plant Sciences and Director of Cambridge University Botanic Garden, for her project Convergent evolution of floral patterning through alternative optimisation of mechanical parameter space.

Glover said: “This funding will enable us to explore how iridescent colour evolved repeatedly in different flowers. We think it will shed new light on evolution itself, as we think about the development of iridescence structure from a mechanical perspective, focusing on the forces acting as a petal grows and the mechanical properties of the petal tissue.

“It's only possible for me to do this work because of the amazing living collection at Cambridge University Botanic Garden, and I'm thrilled that the ERC is keen to support it."

Professor Ian Henderson in the Department of Plant Sciences for his project Evolution of the Arabidopsis Pancentromere.

Henderson said: “This project seeks to investigate enigmatic regions of the genome called the centromeres, using the model plant Arabidopsis. These regions play a deeply conserved role in cell division yet paradoxically are fast evolving.

“I am highly honoured and excited to be awarded an ERC Advanced grant. The advent of long-read sequencing technology makes addressing these questions timely. The ERC’s long-term support will allow us to capitalise on these advances, build new collaborations, and train postdoctoral researchers.”

Professor Paul Lane in the Department of Archaeology, for his project Landscape Historical Ecology and Archaeology of Ancient Pastoral Societies in Kenya.

Lane said: “Pastoralism has been an extraordinarily resilient livelihood strategy across Africa. This project provides an excellent opportunity to reconstruct how East Africa’s pastoralists responded to significant climate change in the past, and to draw lessons from these adaptations for responding to contemporary climate crises in a region that is witnessing heightened water scarcity and loss of access to critically important grazing lands.”

“This project will allow us to utilise the department’s world-leading archaeological science laboratories and expertise to answer crucial questions about past patterns of mobility, dietary diversity, climatic regimes and food security among East African pastoralists over the last fifteen hundred years. This has never been attempted before for this time period.”

Professor Anne Ferguson-Smith, Pro-Vice Chancellor for Research at the University of Cambridge said: “Many congratulations to Albert, Beverley, Ian and Paul on receiving these prestigious and highly competitive awards. It is fantastic that their ambitious, cutting-edge research will be supported by the European Research Council, marking them as outstanding European research leaders.

“Now that the UK is an associated country to Horizon Europe I encourage other Cambridge researchers to also consider applying to the ERC and other Horizon Europe programmes.”

President of the European Research Council Professor Maria Leptin said: “Congratulations to the 255 researchers who will receive grants to follow their scientific instinct in this new funding round. I am particularly happy to see more mid-career scientists amongst the Advanced Grant winners this time. I hope that it will encourage more researchers at this career stage to apply for these grants.”

The ERC is the premier European funding organisation for excellent frontier research. The 255 ERC Advanced Grants, totalling €652 million, support cutting-edge research in a wide range of fields from medicine and physics to social sciences and humanities.

The European Commission and the UK Government have reached an agreement on the association of the UK to Horizon Europe, which applies for calls for proposals implementing the 2024 budget and onwards.

The ERC Advanced Grants target established, leading researchers with a proven track-record of significant achievements. In recent years, there has been a steady rise in mid-career researchers (12-17 years post-PhD), who have been successful in the Advanced Grants competitions, with 18% securing grants in this latest round.

The funding provides leading senior researchers with the opportunity to pursue ambitious, curiosity-driven projects that could lead to major scientific breakthroughs.

Many congratulations to Albert, Beverley, Ian and Paul... It is fantastic that their ambitious, cutting-edge research will be supported by the European Research Council, marking them as outstanding European research leaders.Anne Ferguson-Smith

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Yes

Researchers have evaluated different types of pig farming – including woodland, organic, free range, RSPCA assured, and Red Tractor certified, to assess each systems’ impact across four areas: land use (representing biodiversity loss), greenhouse gas emissions, antibiotics use and animal welfare. Their study concludes that none of the farm types performed consistently well across all four areas – a finding that has important implications for increasingly climate conscious consumers, as well as farmers themselves.

However, there were individual farms that did perform well in all domains, including an indoor Red Tractor farm, an outdoor bred, indoor finished RSPCA assured farm and fully outdoor woodland farm. “Outliers like these show that trade-offs are not inevitable,” said lead author Dr Harriet Bartlett, Research Associate at the University of Oxford's Smith School of Enterprise and the Environment, who was formerly at the University of Cambridge.  

“Somewhat unexpectedly we found that a handful of farms perform far better than average across all four of our environmental and welfare measures,” added senior author Andrew Balmford, Professor of Conservation Science at the University of Cambridge. However, none of the current label or assurance schemes predicted which farms these would be.

“The way we classify farm types and label pork isn’t helpful for making informed decisions when it comes to buying more sustainable meat. Even more importantly, we aren’t rewarding and incentivising the best-performing farmers. Instead of focusing on farm types or practices, we need to focus on meaningful outcomes for people, the planet and the pigs – and assess, and reward farms based on these,” said Bartlett.

The findings also show that common assumptions around food labelling can be misplaced. For instance, Organic farming systems, which consumers might see as climate and environmentally friendly, have on average three times the CO2 output per kg of meat of more intensive Red Tractor or RSPCA assured systems and four times the land use. However, these same systems use on average almost 90% fewer antibiotic medicines, and result in improved animal welfare compared with production from Red tractor or RSPCA assured systems.

The way we classify livestock farms must be improved, Bartlett says, because livestock production is growing rapidly, especially pork production, which has quadrupled in the past 50 years and already accounts for 9% of greenhouse gas emissions from livestock. Pig farming also uses more antibiotics than any other livestock sector, and 8.5% of all arable land.

“Our findings show that mitigating the environmental impacts of livestock farming isn’t a case of saying which farm type is the best,” said Bartlett. “There is substantial scope for improvement within types, and our current means of classification is not identifying the best farms for the planet and animals overall. Instead, we need to identify farms that successfully limit their impacts across all areas of societal concern, and understand, promote and incentivise their practises.”

The study reached its conclusions using data from 74 UK and 17 Brazilian breed-to-finish systems, each made up of 1-3 farms and representing the annual production of over 1.2 million pigs. It is published today in the journal Nature Food.

“To the best of our knowledge, our dataset covers by far the largest and most diverse sample of pig production systems examined in any single study,” said Bartlett.

James Wood, Professor of Equine and Farm Animal Science at the University of Cambridge, commented: “This important study identifies a key need to clarify what different farm labels should indicate to consumers; there is a pressing need to extend this work into other farming sectors. It also clearly demonstrates the critical importance that individual farmers play in promoting best practice across all farming systems.”

Trade-offs in the externalities of pig production are not inevitable was authored by academics at the University of Oxford, University of Cambridge and the University of São Paulo.

The research was funded by the Biotechnology and Biological Sciences Research Council (BBSRC).

Reference: Bartlett, H.,‘Trade-offs in the externalities of pig production are not inevitable.’ Nature Food, April 2024. DOI: 10.1038/s43016-024-00921-2

Adapted from a press release by the University of Oxford.

Farmers don’t have to choose between lowering environmental impact and improving welfare for their pigs, a new study has found: it is possible to do both. But this is not reflected in the current food labelling schemes relied on by consumers.

The way we classify farm types and label pork isn’t helpful for making informed decisions when it comes to buying more sustainable meat.Harriet BartlettCharity Burggraaf/ GettyTwo pigs on a farm

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YesLicence type: Attribution-Noncommerical

The source of pollutants in rivers and freshwater lakes can now be identified using a comprehensive new water quality analysis, according to scientists at the University of Cambridge and Trent University, Canada.

Microparticles from car tyres, pesticides from farmers’ fields, and toxins from harmful algal blooms are just some of the organic chemicals that can be detected using the new approach, which also indicates the impact these chemicals are likely to have in a particular river or lake.

Importantly, the approach can also point to the origin of specific organic matter dissolved in the water, because it has a distinct composition depending on its source.

The approach uses a technique called high-resolution mass spectrometry to analyse water samples: within an hour this provides a comprehensive overview of all the organic molecules present.

Water quality is strongly determined by the diversity of organic matter dissolved in it – termed ‘chemodiversity.’ The scientists say that the thousands of different dissolved organic compounds can keep freshwater ecosystems healthy, or contribute to their decline, depending on the mixture present.

The paper is published today in the journal Science.

“Traditional approaches to monitoring water quality involve taking lots of different measurements with many devices, which takes a lot of time. Our technique is a very simple way to get a comprehensive overview of what’s going on in a particular river or lake,” said Jérémy Fonvielle, a researcher in the University of Cambridge’s Departments of Plant Sciences and Biochemistry, and co-author of the paper.

To understand what drives this chemodiversity, the team reviewed studies of dissolved organic matter in freshwater samples from rivers and lakes across Europe and northern Canada.

For example, water analysis of Lake Erie in Canada revealed high levels of phosphorus pollution. By looking at the composition of individual molecules in the water sample, researchers identified agricultural activities as the source of this pollution, rather than wastewater effluent. 

“Whereas before, we could measure the amount of organic nitrogen or phosphorus pollution in a river, we couldn't really identify where pollution was coming from. With our new approach we can use the unique molecular fingerprint of different sources of pollution in freshwater to identify their source,” said Dr Andrew Tanentzap at Trent University School of the Environment, co-author of the report.

Traditional approaches involve separately measuring many indicators of ecosystem health, such as the level of organic nutrients or particular pollutants like nitrogen. These can indicate the condition of the water, but not why this state has arisen.

Dissolved organic matter is one of the most complex mixtures on Earth. It consists of thousands of individual molecules, each with their own unique properties. This matter influences many processes in rivers and lakes, including nutrient cycling, carbon storage, light absorption, and food web interactions - which together determine ecosystem function.

Sources of dissolved organic matter in freshwater include urban runoff, agricultural runoff, aerosols and wildfires.

“It's possible to monitor the health of freshwater through the diversity of compounds that are present. Our approach can, and is, being rolled out across the UK,” said Tanentzap.

Fonvielle will now apply this technique to analysing water samples from farmland drainage ditches in the Fens, as part of a project run by the University of Cambridge’s Centre for Landscape Regeneration to understand freshwater health in this agricultural landscape.

The research was funded primarily by the Natural Sciences and Engineering Research Council and the European Research Council.

Reference: Tanentzap, A.J. and Fonvielle, J.A: ‘Chemodiversity in freshwater health.’ Science, March 2024. DOI: 10.1126/science.adg8658

Analysing the diversity of organic compounds dissolved in freshwater provides a reliable measure of ecosystem health, say scientists.

Our technique is a very simple way to get a comprehensive overview of what’s going on in a particular river or lake.Jérémy FonvielleSam WoodmanStudy lake in Norway

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The research, led by the University of Cambridge and Penn State University, improves prospects for the elimination and control of bovine tuberculosis (TB), an infectious disease of cattle that results in large economic costs and health impacts across the world.  

This is the first study to show that BCG-vaccinated cattle infected with TB are substantially less infectious to other cattle. This remarkable indirect effect of the vaccine beyond its direct protective effect has not been measured before.

The spillover of infection from livestock has been estimated to account for about 10% of human tuberculosis cases. While such zoonotic TB (zTB) infections are most commonly associated with gastro-intestinal infections related to drinking contaminated milk, zTB can also cause chronic lung infections in humans. Lung disease caused by zTB can be indistinguishable from regular tuberculosis, but is more difficult to treat due to natural antibiotic resistance in the cattle bacteria.

TB remains endemic in many countries around the world, including in Europe and the Americas, where its control costs farmers and taxpayers hundreds of millions of dollars each year.

The study is published today in the journal Science.

In the study, carried out in Ethiopia, researchers examined the ability of the vaccine, Bacillus Calmette-Guérin (BCG), to directly protect cattle that receive it, as well as to indirectly protect both vaccinated and unvaccinated cattle by reducing TB transmission. Vaccinated and unvaccinated animals were put into enclosures with naturally infected animals, in a novel crossover design performed over two years.

“Our study found that BCG vaccination reduces TB transmission in cattle by almost 90%. Vaccinated cows also developed significantly fewer visible signs of TB than unvaccinated ones. This suggests that the vaccination not only reduces the progression of the disease, but that if vaccinated animals become infected, they are substantially less infectious to others,” said Andrew Conlan, Associate Professor of Epidemiology at the University of Cambridge’s Department of Veterinary Medicine and a corresponding author of the study.

Using livestock census and movement data from Ethiopia, the team developed a transmission model to explore the potential for routine vaccination to control bovine tuberculosis.

“Results of the model suggest that vaccinating calves within the dairy sector of Ethiopia could reduce the reproduction number of the bacterium — the R0 — to below 1, arresting the projected increase in the burden of disease and putting herds on a pathway towards elimination of TB,” Conlan said.

The team focused their studies in Ethiopia, a country with the largest cattle herd in Africa and a rapidly growing dairy sector that has a growing burden of bovine tuberculosis and no current control program, as a representative of similarly situated transitional economies.

“Bovine tuberculosis is largely uncontrolled in low- and middle-income countries, including Ethiopia,” said Abebe Fromsa, associate professor of agriculture and veterinary medicine at Addis Ababa University in Ethiopia and the study’s co-lead author. “Vaccination of cattle has the potential to provide significant benefits in these regions.”

“For over a hundred years, programs to eliminate bovine tuberculosis have relied on intensive testing and slaughtering of infected animals,” said Vivek Kapur, professor of microbiology and infectious diseases and Huck Distinguished Chair in Global Health at Penn State and a corresponding author of the study.

He added: “This approach is unimplementable in many parts of the world for economic and social reasons, resulting in considerable animal suffering and economic losses from lost productivity, alongside an increased risk of spillover of infection to humans. By vaccinating cattle, we hope to be able to protect both cattle and humans from the consequences of this devastating disease.”

Professor James Wood, Alborada Professor of Equine and Farm Animal Science in the University of Cambridge’s Department of Veterinary Medicine, noted that despite TB being more prevalent in lower-income countries, the United Kingdom, Ireland and New Zealand also experience considerable economic pressures from the disease which continues to persist despite intensive and costly control programs.

Wood said: “For over twenty-years the UK government has pinned hopes on cattle vaccination for bovine tuberculosis as a solution to reduce the disease and the consequent costs of the controls. These results provide important support for the epidemiological benefit that cattle vaccination could have to reduce rates of transmission to and within herds.”

This research was supported by The Bill & Melinda Gates Foundation, as well as the Biotechnology and Biological Sciences Research Council; Foreign, Commonwealth and Development Office; Economic & Social Research Council; Medical Research Council; Natural Environment Research Council; and Defence Science & Technology.

Reference: Fromsa, A. et al: ‘BCG vaccination of cattle reduces transmission of bovine tuberculosis, improving the prospects for elimination.’ Science, March 2024. DOI: 10.1126/science.adl3962

Vaccination not only reduces the severity of TB in infected cattle, but reduces its spread in dairy herds by 89%, research finds.

Our study suggests that vaccination not only reduces the progression of the disease, but that if vaccinated animals become infected, they are substantially less infectious to others.Andrew ConlanGetty/ kamisokaHerd of cows in a grassy field

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YesLicence type: Attribution-Noncommerical

Everyone has BRCA1 and BRCA2 genes, but mutations in these genes - which can be inherited - increase the risk of breast and ovarian cancer.

The study found that the immune cells in breast tissue of healthy women carrying BRCA1 or BRCA2 gene mutations show signs of malfunction known as ‘exhaustion’. This suggests that the immune cells can’t clear out damaged breast cells, which can eventually develop into breast cancer.

This is the first time that ‘exhausted’ immune cells have been reported in non-cancerous breast tissues at such scale - normally these cells are only found in late-stage tumours.

The results raise the possibility of using existing immunotherapy drugs as early intervention to prevent breast cancer developing, in carriers of BRCA1 and BRCA2 gene mutations.

The researchers have received a ‘Biology to Prevention Award’ from Cancer Research UK to trial this preventative approach in mice. If effective, this will pave the way to a pilot clinical trial in women carrying BRCA gene mutations.

“Our results suggest that in carriers of BRCA mutations, the immune system is failing to kill off damaged breast cells - which in turn seem to be working to keep these immune cells at bay,” said Professor Walid Khaled in the University of Cambridge’s Department of Pharmacology and Wellcome-MRC Cambridge Stem Cell Institute, senior author of the report.

He added: “We’re very excited about this discovery, because it opens up potential for a preventative treatment other than surgery for carriers of BRCA breast cancer gene mutations.

“Drugs already exist that can overcome this block in immune cell function, but so far, they’ve only been approved for late-stage disease. No-one has really considered using them in a preventative way before.”

The results are published today in the journal Nature Genetics.

Risk-reducing surgery, in which the breasts are removed, is offered to those at increased risk of breast cancer. This can be a difficult decision for young women to make and can have a significant effect on body image and sexual relationships.

“The best way to prevent breast cancer is to really understand how it develops in the first place. Then we can identify these early changes and intervene,” said Khaled.

He added: “Late-stage breast cancer tends to be very unpredictable and hard to manage. As we make better and better drugs, the tumours just seem to find a way around it.”

Using samples of healthy breast tissue collected from 55 women across a range of ages, the researchers catalogued over 800,000 cells - including all the different types of breast cell.

The resulting Human Breast Cell Atlas is now available as a resource for other researchers to use and add to. It contains huge amounts of information on other risk factors for breast cancer including Body Mass Index (BMI), menopausal status, contraceptive use and alcohol consumption.

“We've found that there are multiple breast cell types that change with pregnancy, and with age, and it’s the combination of these effects - and others - that drives the overall risk of breast cancer,” said Austin Reed, a PhD student in the University of Cambridge’s Department of Pharmacology and joint first author of the report.

He added: “As we collect more of this type of information from samples around the world, we can learn more about how breast cancer develops and the impact of different risk factors - with the aim of improving treatment.”

One of the biggest challenges in treating breast cancer is that it is not just one disease, but many. Many different genetic variations can lead to breast cancer, and genetic risk interacts with other risk factors in complicated ways.

For example, it is known that the likelihood of breast cancer increases with age, but this risk is greatly reduced by pregnancy early in life. And age-associated risk is greatly increased in carriers of the breast cancer genes BRCA1 and BRCA2.

The new study aimed to understand how some of these risk factors interact, by characterising the different cell types in the human breast under many different physiological states.

The researchers used a technique called ‘single cell RNA-sequencing’ to characterise the many different breast cell types and states. Almost all cells in the body have the same set of genes, but only a subset of these are switched on in each cell – and these determine the cell’s identity and function. Single cell RNA-sequencing reveals which genes are switched on in individual cells.

“Breast cancer occurs around the world, but social inequalities mean not everyone has access to treatment. Prevention is the most cost-effective approach. It not only tackles inequality, which mostly affects low-income countries, but also improves disease outcome in high-income countries,” said Dr Sara Pensa, Senior Research Associate in the University of Cambridge’s Department of Pharmacology and joint first author of the study.

Breast tissue samples were provided by the Breast Cancer Now tissue bank.

The research was primarily funded by the Medical Research Council and Cancer Research UK.

Reference: Reed, A.D. et al: ‘A human breast cell atlas enables mapping of homeostatic cellular shifts in the adult breast.’ Nature Genetics, March 2024. DOI: 10.1038/s41588-024-01688-9

Researchers at the University of Cambridge have created the world’s largest catalogue of human breast cells, which has revealed early cell changes in healthy carriers of BRCA1 and BRCA2 gene mutations.

We’re very excited about this discovery, because it opens up potential for a preventative treatment other than surgery for carriers of BRCA breast cancer gene mutations.Walid KhaledAngiola Harry on UnsplashWoman holds pink breast cancer awareness ribbon. Credit angiola-harry-unsplash

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YesLicence type: Attribution-Noncommerical

Scientists found that farmed salmon production leads to an overall loss of essential dietary nutrients. They say that eating more wild ‘feed’ species directly could benefit our health while reducing aquaculture demand for finite marine resources.

Researchers analysed the flow of nutrients from the edible species of wild fish used as feed, to the farmed salmon they were fed to. They found a decrease in six out of nine nutrients in the salmon fillet – calcium, iodine, iron, omega-3, vitamin B12 and vitamin A, but increased levels of selenium and zinc.

Most wild ‘feed’ fish met dietary nutrient recommendations at smaller portion sizes than farmed Atlantic salmon, including omega-3 fatty acids which are known to reduce the risk of cardiovascular disease and stroke.

“What we’re seeing is that most species of wild fish used as feed have a similar or greater density and range of micronutrients than farmed salmon fillets,” said lead author, Dr David Willer, Zoology Department, University of Cambridge.

“Whilst still enjoying eating salmon and supporting sustainable growth in the sector, people should consider eating a greater and wider variety of wild fish species like sardines, mackerel and anchovies, to get more essential nutrients straight to their plate.”

In the UK, 71% of adults have insufficient vitamin D in winter, and teenage girls and women often have deficiencies of iodine, selenium and iron. Yet while, 24% of adults ate salmon weekly, only 5.4% ate mackerel, 1% anchovies and just 0.4% herring.

“Making a few small changes to our diet around the type of fish that we eat can go a long way to changing some of these deficiencies and increasing the health of both our population and planet,” said Willer.

The researchers found consuming one-third of current food-grade wild feed fish directly would be the most efficient way of maximising nutrients from the sea.

“Marine fisheries are important local and global food systems, but large catches are being diverted towards farm feeds. Prioritising nutritious seafood for people can help improve both diets and ocean sustainability,” said senior author Dr James Robinson, Lancaster University.

This approach could help address global nutrient deficiencies say the team of scientists from the University of Cambridge, Lancaster University, University of Stirling and the University of Aberdeen.

The study was published today in the journal, Nature Food. 

The scientists calculated the balance of nutrients in edible portions of whole wild fish, used within pelleted salmon feed in Norway, compared to the farmed salmon fillets.

They focused on nine nutrients that are essential in human diets and concentrated in seafood – iodine, calcium, iron, vitamin B12, vitamin A, omega-3 (EPA + DHA), vitamin D, zinc and selenium.

The wild fish studied included Pacific and Peruvian anchoveta, and Atlantic herring, mackerel, sprat and blue whiting – which are all marketed and consumed as seafood.

They found that these six feed species contained a greater, or similar, concentration of nutrients as the farmed salmon fillets. Quantities of calcium were over five times higher in wild feed fish fillets than salmon fillets, iodine was four times higher, and iron, omega-3, vitamin B12, and vitamin A were over 1.5 times higher.

Wild feed species and salmon had comparable quantities of vitamin D.

Zinc and selenium were found to be higher in salmon than the wild feed species – the researchers say these extra quantities are due to other salmon feed ingredients and are a real mark of progress in the salmon sector.

“Farmed salmon is an excellent source of nutrition, and is one of the best converters of feed of any farmed animal, but for the industry to grow it needs to become better at retaining key nutrients that it is fed. This can be done through more strategic use of feed ingredients, including from fishery by-products and sustainably-sourced, industrial-grade fish such as sand eels”, said Dr Richard Newton of the Institute of Aquaculture, University of Stirling, whose team also included Professor Dave Little, Dr Wesley Malcorps and Björn Kok.

 “It was interesting to see that we’re effectively wasting around 80% of the calcium and iodine from the feed fish – especially when we consider that women and teenage girls are often not getting enough of these nutrients”.

Willer said “These numbers have been underacknowledged by the aquaculture industry’s standard model of quoting Fish In Fish Out (FIFO) ratios rather than looking at nutrients.

The researchers would like to see a nutrient retention metric adopted by the fishing and aquaculture industries. They believe that if combined with the current FIFO ratio, the industry could become more efficient, and reduce the burden on fish stocks that also provide seafood. The team are building a standardised and robust vehicle for integrating the nutrient retention metric into industry practice.

“We’d like to see the industry expand but not at a cost to our oceans,” said Willer.

“We’d also like to see a greater variety of affordable, convenient and appealing products made of wild ‘feed’ fish and fish and salmon by-products for direct human consumption.”

The research was funded by the Scottish Government’s Rural and Environmental Science and Analytical Services Division (RESAS), a Royal Society University Research Fellowship, a Leverhulme Trust Early Career Fellowship a Henslow Fellowship at Murray Edwards College and the University of Cambridge.

Reference: D. Willer et al. Wild fish consumption can balance nutrient retention in farmed fish Nature Food DOI: 10.1038/s43016-024-00932-z

The public are being encouraged to eat more wild fish, such as mackerel, anchovies and herring, which are often used within farmed salmon feeds. These oily fish contain essential nutrients including calcium, B12 and omega-3 but some are lost from our diets when we just eat the salmon fillet.

Making a few small changes to our diet around the type of fish that we eat can go a long way to changing some of these deficiencies and increasing the health of both our population and planet Dr David Willer, Zoology DepartmentJoff Lee / The Image Bank / Getty Mackerel with potato salad

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Yes

This obesity-driving combination means that dog owners must be particularly strict with feeding and exercising their Labradors to keep them slim.

The mutation is in a gene called POMC, which plays a critical role in hunger and energy use.

Around 25% of Labradors and 66% of flatcoated retriever dogs have the POMC mutation, which researchers previously showed causes increased interest in food and risk of obesity.

The new study reveals how the mutation profoundly changes the way Labradors and flatcoated retrievers behave around food. It found that although they don’t need to eat more to feel full, they are hungrier in between meals.

In addition, dogs with the POMC mutation were found to use around 25% less energy at rest than dogs without it, meaning they don’t need to consume as many calories to maintain a healthy body weight.

“We found that a mutation in the POMC gene seems to make dogs hungrier. Affected dogs tend to overeat because they get hungry between meals more quickly than dogs without the mutation,” said Dr Eleanor Raffan, a researcher in the University of Cambridge’s Department of Physiology, Development and Neuroscience who led the study.

She added: “All owners of Labradors and flatcoated retrievers need to watch what they’re feeding these highly food-motivated dogs, to keep them a healthy weight. But dogs with this genetic mutation face a double whammy: they not only want to eat more, but also need fewer calories because they’re not burning them off as fast.”

The POMC mutation was found to alter a pathway in the dogs’ brains associated with body weight regulation. The mutation triggers a starvation signal that tells their body to increase food intake and conserve energy, despite this being unnecessary.

The results are published today in the journal Science Advances.

Raffan said: “People are often rude about the owners of fat dogs, blaming them for not properly managing their dogs’ diet and exercise. But we’ve shown that Labradors with this genetic mutation are looking for food all the time, trying to increase their energy intake. It’s very difficult to keep these dogs slim, but it can be done.”

The researchers say owners can keep their retrievers distracted from this constant hunger by spreading out each daily food ration, for example by using puzzle feeders or scattering the food around the garden so it takes longer to eat.

In the study, 87 adult pet Labrador dogs - all a healthy weight or moderately overweight - took part in several tests including the ‘sausage in a box’ test.

First, the dogs were given a can of dogfood every 20 minutes until they chose not to eat any more. All ate huge amounts of food, but the dogs with the POMC mutation didn’t eat more than those without it. This showed that they all feel full with a similar amount of food.

Next, on a different day, the dogs were fed a standard amount of breakfast. Exactly three hours later they were offered a sausage in a box and their behaviour was recorded. The box was made of clear plastic with a perforated lid, so the dogs could see and smell the sausage, but couldn’t eat it.

The researchers found that dogs with the POMC mutation tried significantly harder to get the sausage from the box than dogs without it, indicating greater hunger.

The dogs were then allowed to sleep in a special chamber that measured the gases they breathed out. This revealed that dogs with the POMC mutation burn around 25% fewer calories than dogs without it.

The POMC gene and the brain pathway it affects are similar in dogs and humans. The new findings are consistent with reports of extreme hunger in humans with POMC mutations, who tend to become obese at an early age and develop a host of clinical problems as a result.

Drugs currently in development for human obesity, underactive sexual desire and certain skin conditions target this brain pathway, so understanding it fully is important.

A mutation in the POMC gene in dogs prevents production of two chemical messengers in the dog brain, beta-melanocyte stimulating hormone (β-MSH) and beta-endorphin, but does not affect production of a third, alpha-melanocyte stimulating hormone (α-MSH).

Further laboratory studies by the team suggest that β-MSH and beta-endorphin are important in determining hunger and moderating energy use, and their role is independent of the presence of α-MSH. This challenges the previous belief, based on research in rats, that early onset human obesity due to POMC mutations is caused only by a lack of α-MSH. Rats don’t produce beta-melanocyte stimulating hormone, but humans and dogs produce both α- and β-MSH.

The research was funded by The Dogs Trust and Wellcome.

Reference: Dittmann, M.T. et al: ‘Low resting metabolic rate and increased hunger due to β-MSH and β-endorphin deletion in a canine model.’ Science Advances, March 2024. DOI: 10.1126/sciadv.adj3823

New research finds around a quarter of Labrador retriever dogs face a double-whammy of feeling hungry all the time and burning fewer calories due to a genetic mutation.

Labradors with this genetic mutation are looking for food all the time, trying to increase their energy intake. It’s very difficult to keep these dogs slim, but it can be done.Eleanor RaffanJane GoodallLabrador retriever dog

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UKRI funding of £3 million is awarded today to support a new research cluster, as part of the MRC National Mouse Genetics Network (MRC NMGN), focused on improving existing models of ageing with the aim of improving lifelong health and wellbeing. The cluster is led by scientists at the Universities of Cambridge and Newcastle.

The MRC NMGN focuses on age-related biological changes in model organisms, particularly the mouse, to try and improve our understanding and diagnosis of the most challenging disease area of our time - and generate therapeutic avenues.

This award brings the UKRI’s total investment in the MRC NMGN to £25 million.

The need to improve how people age has become a major requirement of modern societies. Regular increases in life expectancy result in older populations, making healthy ageing essential for a better quality of life and a reduced burden on health and social services. 

Understanding the biological mechanisms underlying the ageing process is paramount for tackling the challenges brought about by our older populations.

The new tools generated as a result of this research will be made available to the scientific community to improve understanding of the ageing process, and to provide a resource for preclinical testing and intervention.

Professor Walid Khaled from Cambridge’s Wellcome-MRC Cambridge Stem Cell Institute and Department of Pharmacology, and Co-lead of the new MRC National Mouse Genetics Network Ageing Cluster, said: “I am very pleased to be co-leading this project from Cambridge and I am looking forward to working with the rest of the team from around the UK. ‘Prevention is better than cure’ and so our project will generate a reference map that we will use in the future to assess interventions that could prevent ageing related health decline.”

Professor Anne Ferguson-Smith, Pro-Vice-Chancellor (Research & International Partnerships) and Arthur Balfour Professor of Genetics at Cambridge, said: "Collaboration is central to our research activities in Cambridge. The new Ageing Cluster is a fine example of multiple institutions working together to add value and bring exciting new insight and expertise to advance the critically important field of healthy ageing. I am proud to be part of this important initiative which can deliver new routes to improved health span."

Professor David Burn, Pro Vice Chancellor, Faculty of Medical Sciences at Newcastle University, added: "I am delighted that Newcastle University is an important part of the UKRI Mouse Genetics Network Ageing Cluster.  This cluster offers researchers the opportunity to develop new animal models so that we may better understand ageing.  This, in turn, will allow us to translate this research into extending healthy lifespan in humans in the future.”

The University is bringing together its world leading expertise to tackle the topic of extending the healthy lifespan. Scientists in the School of Biological Sciences are addressing some of the biggest questions in human biology, including: What if we could identify those at risk of developing chronic age-related conditions before they present in the clinic? What if we could intervene before any symptoms arise and prevent disease onset?

UKRI’s strategy for 2022-2027 aims to harness the full power of the UK’s research and innovation system to tackle major national and global challenges. A total of £75m has been allocated to the theme of Securing better health, ageing and wellbeing, which aims to improve population health, tackle the health inequalities affecting people and communities, and advance interventions that keep us healthier for longer.

Read more about Cambridge research into extending the healthy lifespan.

The University of Cambridge has received UKRI funding for research on age-related biological changes in model organisms as part of a national collaboration.

‘Prevention is better than cure’ and so our project will generate a reference map that we will use in the future to assess interventions that could prevent ageing related health declineWalid KhaledUnderstanding Animal ResearchBrown GM mouse on hand

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To mark the International Day of Women and Girls in Science , two of our academics speak about their research careers and how they ended up using their STEM interests to tackle climate change.

The winners of a new prize supporting ambitious ideas for how artificial intelligence can address critical societal issues are announced today, with projects spanning fertility, climate change, language and communication challenges, mental health, and how local councils deploy AI.

The study, published today in Cell Stem Cell, shows that it is possible to experiment on a developing human placenta, rather than merely observe specimens, in order to study major disorders of pregnancy.

Successful pregnancy depends on the development of the placenta in the first few weeks of gestation. During this period, the placenta implants itself into the endometrium – the mucosal lining of the mother’s uterus.

Interactions between the cells of the endometrium and the cells of the placenta are critical to whether a pregnancy is successful. In particular, these interactions are essential to increase the maternal blood supply to the placenta, necessary for fetal growth and development.

When these interactions do not work properly, they can lead to complications, such as pre-eclampsia, a condition that causes high blood pressure during pregnancy. Pre-eclampsia occurs in around six in 100 first pregnancies and can put at risk the health of both the mother and the baby.

Professor Ashley Moffett from the Department of Pathology at the University of Cambridge said: “Most of the major disorders of pregnancy – pre-eclampsia, still birth, growth restriction, for example – depend on failings in the way the placenta develops in the first few weeks. This is a process that is incredibly difficult to study – the period after implantation, when the placenta embeds itself into the endometrium, is often described as a ‘black box of human development’.

“Over the past few years, many scientists – including several at Cambridge – have developed embryo-like models to help us understand early pre-implantation development. But further development is impeded because we understand so little about the interactions between the placenta and the uterus.”

Professor Moffett and colleagues at the Friedrich Miescher Institute, Switzerland, and the Wellcome Sanger Institute, Cambridge, have used ‘mini-placentas’ – a cellular model of the early stages of the placenta – to provide a window into early pregnancy and help improve our understanding of reproductive disorders. Known as ‘trophoblast organoids’, these are grown from placenta cells and model the early placenta so closely that they have previously been shown to record a positive response on an over-the-counter pregnancy test.

In previous work, Professor Moffett and colleagues identified genes that increase the risk of or protect against conditions such as pre-eclampsia. These highlighted the important role of immune cells uniquely found in the uterus, known as ‘uterine natural killer cells’, which cluster in the lining of the womb at the site where the placenta implants. These cells mediate the interactions between the endometrium and the cells of the placenta.

In their new study, her team applied proteins secreted by the uterine natural killer cells to the trophoblast organoids so that they could mimic the conditions where the placenta implants itself. They identified particular proteins that were crucial to helping the organoids develop. These proteins will contribute to successful implantation, allowing the placenta to invade the uterus and transform the mother’s arteries.

“This is the only time that we know of where a normal cell invades and transforms an artery, and these cells are coming from another individual, the baby,” said Professor Moffett, who is also a Fellow at King’s College, Cambridge.

“If the cells aren’t able to invade properly, the arteries in the womb don’t open up and so the placenta – and therefore the baby – are starved of nutrients and oxygen. That's why you get problems later on in pregnancy, when there just isn't enough blood to feed the baby and it either dies or is very tiny.”

The researchers also found several genes that regulate blood flow and help with this implantation, which Professor Moffett says provide pointers for future research to better understand pre-eclampsia and similar disorders.

Dr Margherita Turco, from the Friedrich Miescher Institute in Switzerland and co-lead of this work, added: “Despite affecting millions of women a year worldwide, we still understand very little about pre-eclampsia. Women usually present with pre-eclampsia at the end of pregnancy, but really to understand it – to predict it and prevent it – we have to look at what's happening in the first few weeks.

“Using ‘mini-placentas’, we can do just that, providing clues as to how and why pre-eclampsia occurs. This has helped us unpick some of the key processes that we should now focus on far more. It shows the power of basic science in helping us understand our fundamental biology, something that we hope will one day make a major difference to the health of mothers and their babies.”

The research was supported by Wellcome, the Royal Society, European Research Council and Medical Research Council.

Reference
Li, Q et al. Human uterine natural killer cells regulate differentiation of extravillous trophoblast early in pregnancy. Cell Stem Cell; 17 Jan 2024; DOI: doi.org/10.1016/j.stem.2023.12.013

Scientists have grown ‘mini-placentas’ in the lab and used them to shed light on how the placenta develops and interacts with the inner lining of the womb – findings that could help scientists better understand and, in future, potentially treat pre-eclampsia.

Most of the major disorders of pregnancy – pre-eclampsia, still birth, growth restriction, for example – depend on failings in the way the placenta develops in the first few weeks. This is a process that is incredibly difficult to study.Ashley MoffettFriedrich Miescher Institute/University of CambridgePlacental organoid (circle in the centre). Trophoblast cells are invading out of the organoid, mimicking placental cells invading the uterus in the early weeks of pregnancy.

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