SARS-CoV-2 is a coronavirus, so named because spike proteins on its surface give it the appearance of a crown (‘corona’). The spike proteins bind to ACE2, a protein receptor found on the surface of cells in our body. Both the spike protein and ACE2 are then cleaved, allowing genetic material from the virus to enter the host cell. The virus manipulates the host cell’s machinery to allow the virus to replicate and spread.

As SARS-CoV-2 divides and replicates, errors in its genetic makeup cause it to mutate. Some mutations make the virus more transmissible or more infectious, some help it evade the immune response, potentially making vaccines less effective, while others have little effect.

Towards the end of 2020, Cambridge scientists observed SARS-CoV-2 mutating in the case of an immunocompromised patient treated with convalescent plasma. In particular, they saw the emergence of a key mutation - the deletion of two amino acids, H69/V70, in the spike protein. This deletion was later found in B1.1.7, the variant that led to the UK being forced once again into strict lockdown in December (now referred to as the ‘Alpha variant’).

Now, in research published in the journal Cell Reports, researchers show that the deletion H69/V70 is present in more than 600,000 SARS-CoV-2 genome sequences worldwide, and has seen global expansion, particularly across much of Europe, Africa and Asia.

The research was led by scientists at the University of Cambridge, MRC-University of Glasgow Centre for Virus Research, The Pirbright Institute, MRC Laboratory of Molecular Biology, and Vir Biotechnology.

Professor Ravi Gupta from the Cambridge Institute of Therapeutic Immunology and Infectious Disease at the University of Cambridge, the study’s senior author, said: “Although we first saw this mutation in an immunocompromised patient and then in the Kent – now ‘Alpha’ – variant, when we looked at samples from around the world, we saw that this mutation has occurred and spread multiple times independently.”

Working under secure conditions, Professor Gupta and colleagues used a harmless form of the virus that displays SARS-CoV-2 spike proteins with the H69/V70 deletion to understand how the spike protein interacts with host cells and what makes this mutation so important.

When they tested this virus against blood sera taken from fifteen individuals who had recovered from infection, they found that the deletion did not allow the virus to ‘escape’ neutralising antibodies made after being vaccinated or after previous infection. Instead, the team found that the deletion makes the virus twice as infective – that is, at breaking into the host’s cells – as a virus that dominated global infections during the latter half of 2020. This was because virus particles carrying the deletion had a greater number of mature spike proteins on their surface. This allows the virus to then replicate efficiently even when it has other mutations that might otherwise hinder the virus. 

“When viruses replicate, any mutations they acquire can act as a double-edged sword: a mutation that enables the virus to evade the immune system might, for example, affect how well it is able to replicate,” said Professor Gupta.

“What we saw with the H69/V70 deletion was that in some cases, the deletion helped the virus compensate for the negative effects that came with other mutations which allowed the virus to escape the immune response. In other words, the deletion allowed these variants to have their cake and eat it – they were both better at escaping immunity and more infectious.”

Dr Dalan Bailey from The Pirbright Institute, who co-led the research, added: “In evolutionary terms, when a virus develops a weakness, it can lead to its demise, but the H69/V70 deletion means that the virus is able to mutate further than it otherwise would. This is likely to explain why these deletions are now so widespread.”

Bo Meng from the Department of Medicine at the University of Cambridge, first author on the paper, said: “Understanding the significance of key mutations is important because it enables us to predict how a new variant might behave in humans when it is first identified. This means we can implement public health and containment strategies early on.”

The research was supported by Wellcome, the Medical Research Council, the Bill & Melinda Gates Foundation and the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre.

Reference
Meng, B, Kemp, SA, Papa, G, Datir R, Ferreira, IATM et al. Recurrent emergence of SARS-CoV-2 spike deletion H69/V70 and its role 1 in the Alpha variant B.1.1.7. Cell Reports; 8 June 2021; DOI: 10.1016/j.celrep.2021.109292 

These particular ceremonies, held in the University’s 18th-century Senate House and known as General Admission to Degrees, will see students from 29 Colleges graduate over four days and have been carefully orchestrated in accordance with social distancing rules for higher education institutions and in consultation with the University’s safety advisers and the City Council. 

Other measures include strict limits on numbers inside the Senate House at one time, maximum ventilation with face coverings worn indoors and students queuing outside before graduating.

Family and friends who would normally attend have been invited to watch the ceremonies, conducted in Latin and in full academic dress, on a private livestream link.  

The University and the Colleges recognise the importance of celebrating the remarkable achievements of our students in a fitting manner that keeps most of the elements of the traditional ceremony while incorporating the necessary precautions.

Pro-Vice-Chancellor (Education) Professor Graham Virgo said:

“Our students have worked incredibly hard and shown resilience and responsibility in their approach to the Covid-19 restrictions. I congratulate them all on their successes, and wish them well for the future.”

In a study published today in Science Advances, a team led by researchers at the University of Cambridge’s Milner Therapeutics Institute and Gurdon Institute used a combination of computational biology and machine learning to create a comprehensive map of proteins that are involved in SARS-CoV-2 infection – from proteins that help the virus break into the host cell to those generated as a consequence of infection. By examining this network using artificial intelligence (AI) approaches, they were able to identify key proteins involved in infection as well as biological pathways that might be targeted by drugs.

To date, the majority of small molecule and antibody approaches for treating COVID-19 are drugs that are either currently the subject of clinical trials or have already been through clinical trials and been approved. Much of the focus has been on several key virus or host targets, or on pathways – such as inflammation – where a drug treatment could be used as an intervention.

The team used computer modelling to carry out a ‘virtual screen’ of almost 2,000 approved drugs and identified 200 approved drugs that could be effective against COVID-19. Forty of these drugs have already entered clinical trials, which the researchers argue supports the approach they have taken.

When the researchers tested a subset of those drugs implicated in viral replication, they found that two in particular – an antimalarial drug and a type of medicine used to treat rheumatoid arthritis – were able to inhibit the virus, providing initial validation of their data-driven approach.

Professor Tony Kouzarides, Director of the Milner Therapeutics Institute, who led the study, said: “By looking across the board at the thousands of proteins that play some role in SARS-CoV-2 infection – whether actively or as a consequence of infections – we’ve been able to create a network uncovering the relationship between these proteins.

“We then used the latest machine learning and computer modelling techniques to identify 200 approved drugs that might help us treat COVID-19. Of these, 160 had not been linked to this infection before. This could give us many more weapons in our armoury to fight back against the virus.”

Using artificial neural network analysis, the team classified the drugs depending on the overarching role of their targets in SARS-CoV-2 infection: those that targeted viral replication and those that targeted the immune response. They then took a subset of those involved in viral replication and tested them using cell lines derived from humans and from non-human primates.

Of particular note were two drugs, sulfasalazine (used to treat conditions such as rheumatoid arthritis and Crohn’s disease) and proguanil (and antimalarial drug), which the team showed reduced SARS-CoV-2 viral replication in cells, raising the possibility of their potential use to prevent infection or to treat COVID-19.

Dr Namshik Han, Head of Computational Research and AI at the Milner Therapeutics Institute, added: “Our study has provided us with unexpected information about the mechanisms underlying COVID-19 and has provided us with some promising drugs that might be repurposed for either treating or preventing infection. While we took a data-driven approach – essentially allowing artificially intelligent algorithms to interrogate datasets – we then validated our findings in the laboratory, confirming the power of our approach.

“We hope this resource of potential drugs will accelerate the development of new drugs against COVID-19. We believe our approach will be useful for responding rapidly to new variants of SARS-CoV2 and other new pathogens that could drive future pandemics.”

The research was funded by LifeArc, the LOEWE Center DRUID, the Bundesministerium für Bildung und Forschung, the European Union’s Horizon 2020 programme, Wellcome and Cancer Research UK.

Reference
Han, N, Hwang, W, Tzelepis, K, & Schmerer, P, et al. Identification of SARS-CoV-2 induced pathways reveal drug repurposing strategies. Sci Adv; 30 June 2021

Supermarkets and food manufacturers have been excessively blamed for Britain’s unhealthy eating habits since the 1980s, according to Cambridge historian Dr Katrina-Louise Moseley.

In an article published in Contemporary British History, Moseley argues that far from being passive victims of manipulation in this period, consumers were ‘complicit’ in long-term behavioural shifts, proactively selecting, rejecting and sweetening advice from the government, the food industry and the media to fit their circumstances and to satisfy their appetites.

Rather than seeking to cast blame, Moseley asserts that we should think more carefully about how people rationalise their eating behaviours and interpret advice about food. Speaking ahead of a public event entitled 'Food on the Move' (9 July 2021), Moseley added that this is particularly relevant in the context of the COVID-19 pandemic, which has had a dramatic impact on eating behaviours.

“Food is a powerful coping mechanism in times of emotional distress, so it isn’t surprising that people have been buying extra packets of their favourite snack or eating more takeaways. I’m interested in the psychology of consumption and getting away from moralising language around food, which can be damaging”, Moseley said. As part of the event, hosted by the University of Warwick, Moseley invites readers to complete an anonymous survey (closes 9 July 2021) to reflect on how their own food practices have changed during the pandemic.

In her article, Moseley contrasts the success of Britain’s anti-smoking campaign, which transformed attitudes to tobacco in the 1960s and 70s, with the failure of the ‘healthy eating’ campaign to counteract rising levels of obesity from the late 1980s onwards.

Moseley said: “The state faced a really difficult task. ‘Don’t smoke’ was a clear-cut message but you can’t tell people not to eat. Food can't be rejected outright, it has to remain a part of everyday life, and that makes it so much more complicated. We’re still really struggling with this today.”

The historian makes fresh use of consumer interviews and surveys conducted in England and Wales in the 1980s and 90s. These include a Mass Observation directive questionnaire on ‘Food and Drink’ completed in 1982; interviews and participant observations gathered from 1992–96 in response to the 1992 Health of the Nation report; and a collection of life history interviews undertaken with a sample of older people in 2017–18. 

Moseley argues that a major problem facing Britain’s ‘healthy eating’ campaign has been its reliance, often unavoidable, on malleable language. Words like ‘balance’ and ‘moderation’ left themselves open to subjective interpretation. Moseley said: “These records reveal all kinds of people, not just the less affluent, leaning towards convenience foods while still trying to define their lifestyles as healthy.”

Looking at the 1982 questionnaire records, Moseley found that attitudes to convenience foods were 'shot through with contradictions'. Speaking for herself and her husband, one female respondent claimed, “neither of us can bear ready-made frozen dinners” – but she made “an exception for certain things from Marks & Spencer – their frozen cod in parsley sauce is palatable and their cauliflower cheese makes me a quick solo meal if Neil is out for the evening.”

Moseley said: “For health enthusiasts and cynics alike, official information about food didn’t always feel correct. Consumers continued to assert that foods had different effects on different individuals, that one could be overweight whilst leading a healthy lifestyle, and that – in the midst of a dizzying array of information, self-evaluation was key.” 

The study describes how supermarkets and food manufacturers seized on the idea of ‘healthy eating’ in the 1980s in response to new nutritional guidelines being issued. In 1984, Heinz began a 25-year-programme to reduce salt and sugar in its products; and in 1986 Mars produced a pamphlet entitled ‘Confectionary in a Healthy Diet’. Meanwhile Tesco and Sainsbury's turned their attention to nutritional labelling. 

Moseley said: “We underestimate what a pivotal role the convenience foods sector played in producing and disseminating knowledge about ‘healthy eating’ in this period. Sometimes, as with Findus’ calorie-controlled ready meals, it was the food industry rather than politicians or doctors that gave people usable, workable public health messages. But increasingly people came to view big food companies, government and public health experts as one and the same: a mysterious force manipulating consumer behaviour.” 

Testimonies collected in the 1980s and 90s emphasise that new jargon baffled many consumers. Puzzling over the term ‘polyunsaturated margarine’, one respondent to the 1980s questionnaire said: “I understand that poly means many and unsaturated means not chock full of something, so what is margarine poly unsaturated with or not with?” In 1985, a market research study of nearly 1,500 consumers in England and Wales found that 43% were uncertain whether saturated or polyunsaturated fat was better for them. 

Moseley said: “Terms like ‘E-numbers’ and ‘saturated fats’ entered public discourse but that didn’t mean that everyone understood or accepted health advice, let alone changed their behaviours. Naturally, people embraced foods that made their lives easier and their mealtimes tastier, often using the language of ‘moderation’ to justify the consumption of highly processed, time-saving foods.”

The study examines the rise of scepticism as consumers felt overloaded with confusing, contradictory and unreliable ‘healthy eating’ messages. The 1992–96 interviews reveal that consumers became increasingly committed to using their ‘common sense’ when thinking about food. Moseley said: “Consumers didn’t respond as authorities hoped they would, but they weren’t irrational or lacking in judgement. People subscribed to their own, highly personalized logics.”

One 1992–96 interviewee said: “some days you just want mashed potatoes and I’m not going to feel bad about that because with the rest of my life… it’s balanced’.” Interviewees also sought reassurance from their childhood eating habits or those of older relatives, saying things like: “Nan lived to a good old age” or “it didn’t seem to do us much harm at the time”.

Testimonies from the 1990s also reveal the emergence of a new language linking food and feeling. One woman defined healthy eating as “that difference between… getting a good feeling from what you eat and getting this sort of not very nice feeling”. “Cheese especially” made another young woman feel “so ugh – you know it makes me feel so fat and just weighs me down”. She added that she felt “much healthier and brighter” if she avoided it. 

Moseley said: “The idea that different foods might cause individuals to feel a certain way in their bodies prefigured a major shift towards self-diagnosed food intolerances in the early twenty-first century.”

The study accepts that some positive health trends did come about in the late 20th century but points out that consumers favoured easier quick-fixes like switching to brown bread and semi-skimmed milk, over sweeping dietary transformations. 

Moseley said: “Medical researchers remain very worried about public scepticism, but their studies tend to lack historical context. Thinking about the history of trust and cynicism alongside developments in public health can help us understand and reconstruct the bigger picture.”

Reflecting on Britain’s food culture today, Moseley points out that economic, social and geographic constraints on ‘healthy’ choices lack public visibility: factors like deprivation, time poverty, and mental illness delimit the choices that consumers feel able to make. She said: “Too often, health education campaigns promote ‘informed’ decision making around food, as if social and economic disparities do not exist. Food has long been a site of inequality in Britain, and unfortunately it remains so today.”

Reference 

K Moseley, ‘From Beveridge Britain to Birds Eye Britain: Shaping knowledge about ‘healthy eating’ in the mid-to-late twentieth-century’, Contemporary British History (2021). DOI: 10.1080/13619462.2021.1915141 

There is significant debate about substance use of autistic adolescents and adults. Some studies indicate that autistic individuals are less likely to use substances, whereas others suggest that autistic individuals are at greater risk of substance misuse or abuse. The team at the Autism Research Centre in Cambridge used a ‘mixed methods’ design to consider both the frequency of substance use among autistic individuals, as well as their self-reported experiences of substance use.

Overall, 1,183 autistic and 1,203 non-autistic adolescents and adults (aged 16-90 years) provided information about the frequency of their substance use via an anonymous, online survey; of this group, 919 individuals also gave more in-depth responses about their experiences of substance use.

Autistic adults were less likely than non-autistic peers to use substances. Only 16% of autistic adults, compared to 22% of non-autistic adults, reported drinking on three or more days per week on average. Similarly, only 4% of autistic adults reported binge-drinking compared to 8% of non-autistic adults.

There were also some sex differences in patterns of substance use: autistic males were less likely than non-autistic males to report ever having smoked or used drugs. In contrast, the team did not find differences in the patterns of frequency of smoking or drug use between autistic and non-autistic females.

However, despite lower rates of substance use overall, the qualitative findings of the study provide a much less hopeful picture: autistic adults were nearly nine times more likely than non-autistic peers to report using recreational drugs (such as marijuana, cocaine and amphetamines)  to manage unwanted symptoms, including autism-related symptoms.

Drugs were used to reduce sensory overload, help with mental focus, and provide routine, among other reasons. Several autistic participants also indirectly referenced using substances to mask their autism. Past research has shown that this behavioural management (also known as ‘camouflaging’ or ‘compensating’) has been linked to emotional exhaustion, worse mental health, and even increased risk of suicide among autistic adults.

Autistic adolescents and adults were also over three times more likely than others to report using substances to manage mental health symptoms, including anxiety, depression, and suicidal thoughts. Several participants specifically noted that they used drugs for self-medication. However, this self-medication was not always viewed as negative by participants, and several noted that using recreational drugs allowed them to reduce the doses of prescribed medications for mental health conditions, which was a welcome change due to the sometimes significant side effects from their prescribed medications.

Another area of concern was the strong association between vulnerability and substance use among autistic teenagers and adults. Previous work from the Cambridge team suggests that autistic adults may be much more likely to have adverse life experiences and be at greater risk of suicide than others. The findings of the new study indicate that autistic individuals are over four times more likely to report vulnerability associated with substance use compared to their non-autistic peers, including dependence/addiction, using drugs to deal with past trauma, and substance use associated with suicide.

In addition, the study identified two new areas of vulnerability not been previously reported: being forced, tricked, or accidentally taking drugs; and childhood use of substances (at the age of 12 years or younger).

Elizabeth Weir, a PhD student at the Autism Research Centre in Cambridge, and the lead researcher of the study, said: “Whether or not the substances currently classed as ‘recreational’ could be used medically remains an open question. It is evident that the current systems of health and social care support are not meeting the needs of many autistic teenagers and adults.

“No one should feel that they need to self-medicate for these issues without guidance from a healthcare professional. Identifying new forms of effective support is urgent considering the complex associations between substance use, mental health, and behaviour management—particularly as camouflaging and compensating behaviours are associated with suicide risk among autistic individuals.”

Dr Carrie Allison, Director of Research Strategy at the Autism Research Centre and a member of the research team, said: “While some of our results suggest lower likelihood of substance use overall, physicians should not assume that their autistic patients aren’t using drugs. Drug use can be harmful so healthcare providers should aim to establish trusting relationships with autistic and non-autistic patients alike to foster frank and honest conversations about substance use.”

Professor Simon Baron-Cohen, Director of the Autism Research Centre and a member of the team, said: “We continue to see new areas in which autistic adults experience vulnerability: mental health, physical health, suicide risk, lifestyle patterns, the criminal justice system, and so on. Substance use is now another area that we need to consider when developing new forms of support for autistic individuals. It is essential that we ensure that autistic people have equal access to high quality social and healthcare that can appropriately support their specific needs; and, unfortunately, it seems clear that our current systems are still not meeting this mark.”

The research was funded by the Autism Research Trust, Rosetrees Trust, Cambridge and Peterborough NHS Foundation Trust, Corbin Charitable Trust, Medical Research Council, Wellcome and the Innovative Medicines Initiative.

Reference
Weir, E., Allison, C., & Baron-Cohen, S. Understanding the substance use of autistic adolescents and adults: a mixed methods approach. The Lancet Psychiatry (2021).

The eruption of the Toba volcano was the largest volcanic eruption in the past two million years, but its impacts on climate and human evolution have been unclear. Resolving this debate is important for understanding environmental changes during a key interval in human evolution.

“We were able to use a large number of climate model simulations to resolve what seemed like a paradox,” said lead author Benjamin Black from Rutgers University. “We know this eruption happened and that past climate modeling has suggested the climate consequences could have been severe, but archaeological and palaeoclimate records from Africa don’t show such a dramatic response.

“Our results suggest that we might not have been looking in the right place to see the climate response. Africa and India are relatively sheltered, whereas North America, Europe and Asia bear the brunt of the cooling. One intriguing aspect of this is that Neanderthals and Denisovans were living in Europe and Asia at this time, so our paper suggests evaluating the effects of the Toba eruption on those populations could merit future investigation.”

The researchers analysed 42 global climate model simulations in which they varied magnitude of sulphur emissions, time of year of the eruption, background climate state and sulfur injection altitude to make a probabilistic assessment of the range of climate disruptions the Toba eruption may have caused.

The results suggest there was likely significant regional variation in climate impacts. The simulations predict cooling in the Northern Hemisphere of at least 4°C, with regional cooling as high as 10°C depending on the model parameters.

In contrast, even under the most severe eruption conditions, cooling in the Southern Hemisphere -- including regions populated by early humans – was unlikely to exceed 4°C, although regions in southern Africa and India may have seen decreases in precipitation at the highest sulphur emission level.

The results explain independent archaeological evidence suggesting the Toba eruption had modest effects on the development of hominid species in Africa. According to the authors, their ensemble simulation approach could be used to better understand other past and future explosive eruptions.

“Our work is not only a forensic analysis of Toba’s aftermath some 74,000 years ago, but also a means of understanding the unevenness of the effects such very large eruptions may have on today’s society,” said co-author Dr Anja Schmidt from the University of Cambridge. “Ultimately, this will help to mitigate the environmental and societal hazards from future volcanic eruptions.”

The study included researchers from the National Center for Atmospheric Research, University of Leeds and University of Cambridge, and was supported by the National Center for Atmospheric Research and the National Science Foundation.

Reference:
Benjamin A. Black et al. ‘Global climate disruption and regional climate shelters after the Toba supereruption.’ PNAS (2021). DOI: 10.1073/pnas.2013046118 |

Adapted from a Rutgers University press release.

Type 2 diabetes is thought to be driven in part by inherited genetic factors, but many of these genes are yet unknown. Previous large-scale studies have depended on efficient ‘array genotyping’ methods to measure genetic variations across the whole genome. This approach typically does a good job at capturing the common genetic differences between people, though individually these each confer only small increases in diabetes risk.

Recent technical advances have allowed more comprehensive genetic measurement by reading the complete DNA sequences of over 20,000 genes that code for proteins in humans. Proteins are essential molecules that enable our bodies to function. In particular, this new approach has allowed for the first time a large-scale approach to study the impact of rare genetic variants on several diseases, including type 2 diabetes.

By looking at data from more than 200,000 adults in the UK Biobank study, researchers from the Medical Research Council (MRC) Epidemiology Unit at the University of Cambridge used this approach to identify genetic variants associated with the loss of the Y chromosome. This is a known biomarker of biological ageing that occurs in a small proportion of circulating white blood cells in men and indicates a weakening in the body’s cellular repair systems. This biomarker has been previously linked to age-related diseases such as type 2 diabetes and cancer.

In results published today in Nature Communications, the researchers identified rare variants in the gene GIGYF1 that substantially increase susceptibility to loss of the Y chromosome, and also increase an individual’s risk of developing type 2 diabetes six-fold. In contrast, common variants associated with type 2 diabetes confer much more modest increases in risk, typically much lower than two-fold.

Around 1 in 3,000 individuals carries such a GIGYF1 genetic variant. Their risk of developing type 2 diabetes is around 30%, compared to around 5% in the wider population. In addition, people who carried these variants had other signs of more widespread ageing, including weaker muscle strength and more body fat.

GIGYF1 is thought to control insulin and cell growth factor signalling. The researchers say their findings identify this as a potential target for future studies to understand the common links between metabolic and cellular ageing, and to inform future treatments.

Dr John Perry, from the MRC Epidemiology Unit and a senior author on the paper, said: “Reading an individual’s DNA is a powerful way of identifying genetic variants that increase our risk of developing certain diseases. For complex diseases such as type 2 diabetes, many variants play a role, but often only increasing our risk by a tiny amount. This particular variant, while rare, has a big impact on an individual’s risk.”

Professor Nick Wareham, Director of the MRC Epidemiology Unit, added: “Our findings highlight the exciting scientific potential of sequencing the genomes of very large numbers of people. We are confident that this approach will bring a rich new era of informative genetic discoveries that will help us better understand common diseases such as type 2 diabetes. By doing this, we can potentially offer better ways to treat – or even to prevent – the condition.”

Ongoing research will aim to understand how the loss of function variants in GIGYF1 lead to such a substantial increase in the risk of developing type 2 diabetes. Their future research will also examine other links between biomarkers of biological ageing in adults and metabolic disorders.

The research was funded by the Medical Research Council. UK Biobank is supported Wellcome, the Medical Research Council, British Heart Foundation, Cancer Research UK, Department of Health, Northwest Regional Development Agency and the Scottish Government.

Reference
Zhao, Y. et al. GIGYF1 loss of function is associated with clonal mosaicism and adverse metabolic health. Nature Communications 2021; 07 Jul 2021; DOI: 10.1038/s41467-021-24504-y

The University of Cambridge is in talks with the United Arab Emirates about a potential strategic partnership. These ongoing conversations have emerged from a shared commitment to creating a more sustainable future by helping to solve some of the greatest challenges facing our planet.

This collaboration is designed to develop innovative solutions that enable the transition away from fossil fuels; the continued development of high quality teaching and learning; the ongoing progression of social cohesion through the study of arts and culture; and the advancement of globally competitive research, education, and entrepreneurship

A University spokesperson said: ‘This is an exciting and unique opportunity for world-leading collaborations on efforts to transform economies and societies. The potential partnership will help prepare education systems for a radically changing labour market, promote greater global understanding through appreciation for Islamic art and culture, and develop innovative technological solutions to the challenges facing our planet, helping the transition away from fossil fuels.’

The United Arab Emirates is a regional and international hub for collaboration in research, art, education and business, in areas as diverse as Mars exploration and celebrating emerging Arab artists. One of the world’s largest investors in renewable energy such as solar power it has bid to host COP28 with a focus on building sustainable economies.

The University of Cambridge and the UAE share an ambition to fight climate change and create sustainable solutions that will help the global economy transition away from fossil fuels. We are excited about the prospect of our students and researchers benefiting from these new connections and perspectives.

The three initial areas of discussions will focus on:

Sustainability

The potential partnership will research and pioneer new ways of moving progressively towards a post-fossil fuel economy and embracing the fourth industrial revolution. A sustainable futures research programme will start with work to advance manufacturing, urban infrastructure and resource management. 

Education

The potential partnership will focus collaboratively on early years education, teacher education, Arabic literacy and blended learning, with a view to developing robust, resilient and coherent systems that can support a 21st-Century labour market.

Arts and Culture

The potential partnership will collaboratively seek to strengthen global understanding of Islamic art and culture, and support the long-term resilience of cultural institutions in both countries for greater social cohesion.

An interdisciplinary team of researchers, led by the Universities of Cambridge and Tübingen, has gathered measurements of body and brain size for over 300 fossils from the genus Homo found across the globe. By combining this data with a reconstruction of the world’s regional climates over the last million years, they have pinpointed the specific climate experienced by each fossil when it was a living human.

The study reveals that the average body size of humans has fluctuated significantly over the last million years, with larger bodies evolving in colder regions. Larger size is thought to act as a buffer against colder temperatures: less heat is lost from a body when its mass is large relative to its surface area. The results are published today in the journal Nature Communications.

Our species, Homo sapiens, emerged around 300,000 years ago in Africa. The genus Homo has existed for much longer, and includes the Neanderthals and other extinct, related species such as Homo habilis and Homo erectus.

A defining trait of the evolution of our genus is a trend of increasing body and brain size; compared to earlier species such as Homo habilis, we are 50% heavier and our brains are three times larger. But the drivers behind such changes remain highly debated.

“Our study indicates that climate - particularly temperature - has been the main driver of changes in body size for the past million years,” said Professor Andrea Manica, a researcher in the University of Cambridge’s Department of Zoology who led the study.

He added: “We can see from people living today that those in warmer climates tend to be smaller, and those living in colder climates tend to be bigger. We now know that the same climatic influences have been at work for the last million years.”

The researchers also looked at the effect of environmental factors on brain size in the genus Homo, but correlations were generally weak. Brain size tended to be larger when Homo was living in habitats with less vegetation, like open steppes and grasslands, but also in ecologically more stable areas. In combination with archaeological data, the results suggest that people living in these habitats hunted large animals as food - a complex task that might have driven the evolution of larger brains.

“We found that different factors determine brain size and body size – they’re not under the same evolutionary pressures. The environment has a much greater influence on our body size than our brain size,” said Dr Manuel Will at the University of Tubingen, Germany, first author of the study.

He added: “There is an indirect environmental influence on brain size in more stable and open areas: the amount of nutrients gained from the environment had to be sufficient to allow for the maintenance and growth of our large and particularly energy-demanding brains.”

This research also suggests that non-environmental factors were more important for driving larger brains than climate, prime candidates being the added cognitive challenges of increasingly complex social lives, more diverse diets, and more sophisticated technology.

The researchers say there is good evidence that human body and brain size continue to evolve. The human physique is still adapting to different temperatures, with on average larger-bodied people living in colder climates today. Brain size in our species appears to have been shrinking since the beginning of the Holocene (around 11,650 years ago). The increasing dependence on technology, such as an outsourcing of complex tasks to computers, may cause brains to shrink even more over the next few thousand years.

“It’s fun to speculate about what will happen to body and brain sizes in the future, but we should be careful not to extrapolate too much based on the last million years because so many factors can change,” said Manica.

This research was funded by the European Research Council and the Antarctic Science Platform.

Reference

Will, M. et al: ‘Different environmental variables predict body and brain size evolution in Homo.’ Nature Communications, July 2021. DOI: 10.1038/s41467-021-24290-7

Women are underrepresented “at almost every level” within the discipline of economics at UK universities, according to a new report co-authored by a Cambridge economist.

Dr Victoria Bateman says that her research for the Royal Economics Society (RES) found signs of “stagnation and retreat” in the closing of gender gaps across the study of economics – with female intake (relative to male) actually falling at both undergraduate and master’s levels over the last two decades.

Published today, the report ‘Gender Imbalance in UK Economics’ marks 25 years since the establishment of the RES Women’s Committee, which was set up to monitor and advance the representation of women in UK economics.

“The economy affects everyone, and economists need to represent us all,” said Bateman, an Economics Fellow at Gonville and Caius College. “If they don’t, that’s a major barrier to building a solid understanding of the economy.”   

“Across all students, from undergraduate to PhD, there are twice as many men studying economics as there are women in UK universities. While in many respects the discipline of economics has come a long way in the 21st century, the gender gap is clearly still real, persistent and in some ways getting worse.”

Bateman and colleagues argue that attracting, retaining and promoting female economists is a “particular problem” within UK academia when compared to areas of government and third sector organisations such as think tanks.

Only a quarter (26%) of economists working in UK academia are female, and only 15% of economics professors are women, compared to 38% of the economists at the UK Treasury and 44% of researchers at economic think tanks.

Among UK students entering the discipline, the gender gap has actually widened since 2002, when 31% of economics undergraduates and 37% of master’s students were women. By 2018, this had fallen to 27% and 31% respectively. Bateman says these statistics show that the closure of the gender gap in economics “isn’t simply a matter of time”.

“Only a third of economics lecturers in the UK are women, and just fifteen percent of economics professors,” said report co-author Dr Erin Hengel, who received her PhD in economics from Cambridge before going on to lecture at the University of Liverpool.

“While these figures are better than they were twenty-five years ago, the improving trend has levelled off. It appears that progress is starting to slow far before we reach any kind of gender parity.”

When the report’s authors factored in ethnicity, the percentage of female students was higher. In 2018, a third (33%) of Black economics undergraduates and 31% of Asian ethnicity undergraduates were women, compared to a quarter (25%) of White students.

However, women from ethnic minority backgrounds are not staying in academic economics. The report also found that at PhD level, the proportion of women is ten percentage points lower among minority candidates than white candidates.

Perhaps startlingly, the report found that between 2012 and 2018 there was not a single Black woman employed as a professor of economics anywhere in the UK.

Bateman says she hopes the new report will serve as a “call to arms” for the discipline of economics. “We are calling on universities to ask themselves why so few UK women are attracted to studying and researching the economy and why, even when they are, they do not stay,” she said. 

Bateman’s 2019 book The Sex Factor showed how the status and freedom of women are central to prosperity, and that “gender blindness” in economics has left the discipline wide of the mark on everything from poverty and inequality to understanding cycles of boom and bust.

“Unless economists are diverse, we cannot hope to build a complete understanding of the economy, and, with it, formulate the right kinds of policies,” Bateman added.

Following the launch of Formula 1’s #WeRaceAsOne initiative last year it set out plans to increase diversity and inclusion across Formula 1, in addition to wider plans set out in its diversity and inclusion strategy in 2019. Formula 1 announced last year that as a sport it would focus specifically on creating employment and education opportunities for underrepresented groups with a personal contribution of $1 million (around £725,000) from Non- Executive Chairman, Chase Carey to finance primarily, but not exclusively, Engineering-focused scholarships for underrepresented students.

Today (14th July), Formula 1 is announcing the Formula 1 Engineering Scholarships, for ten students from underrepresented groups including ethnic minorities, women, and those from lower socio-economic backgrounds. Each scholarship will provide the full cost of a student’s tuition, together with a living stipend. The scholars will be part of the September/October 2021 intake of undergraduate courses in the UK and Masters (Postgraduate) in Italy. All ten Formula 1 teams have committed to provide work experience opportunities to a scholar during their time at university. The participating universities represent different regions within the UK and Italy, and each will run an independent selection process to determine the scholarship recipients. Alongside Cambridge, Formula 1 is partnering with Coventry, Manchester Metropolitan, MUNER Motor vehicle University (Italy), Oxford, and Strathclyde.

As well as the Scholarship programme, Formula 1 is launching an Apprentice Programme and Internship Programme for underrepresented groups.

Stefano Domenicali, President and CEO of Formula 1 said:

"Formula 1 is a global sport with fans across the world. We want to be as diverse as our fan base and that is why we are taking action to ensure talented people from underrepresented groups have the best opportunities to get into, and build, a fantastic career in this amazing sport. I am delighted to announce that scholars, apprentices and interns will get the chance to fulfil their dreams in Formula 1 and I know they have amazing futures ahead of them. I want to pay particular thanks to Chase whose generous donation is funding the ten scholarships."

"Our #WeRaceAsOne platform is our commitment to make real change and shows our recognition that we know we must make a positive contribution to the world we live in. All of the teams are committed to this and the work of the Hamilton Commission shows the dedication to addressing these issues across Formula 1. Our focus is on Diversity & Inclusion, Sustainability and Community and we will continue to drive forward with our plans to be more diverse, more sustainable and leave a lasting positive impact on the countries and communities we visit. We know we must continue to move forward on these issues and the whole sport is united in doing this in the months and years ahead."

Professor Richard Prager, the Head of the University of Cambridge’s Engineering Dept, said:

"We are incredibly grateful to Formula 1 for providing a student with this generous scholarship. Engineering is about problem solving, creativity and team-work, which all benefit greatly from a diverse and inclusive environment. This scholarship will highlight the importance of this priority for the Department of Engineering and the wider University and hopefully encourage many other students from currently underrepresented backgrounds to consider studying engineering at Cambridge."

The University of Cambridge will this year pilot two summer schools as part of efforts to encourage more students from underrepresented backgrounds to apply for postgraduate study.

Experience Postgrad Life Sciences, and the SHARE programme in the social sciences, will each offer undergraduates from universities across the UK and Ireland an introduction to postgraduate study, vital practical research experience and support through the application process.

The two summer schools are part of Cambridge’s commitment to diversifying representation among postgraduates, along with the appointment of a Postgraduate Widening Participation Manager, Dr Katherine Powlesland, and recent re-assessment of the University’s postgraduate admissions practices to better support students from underrepresented backgrounds in making competitive applications. The University is also working to boost the number of Master’s studentships for postgraduate students from underrepresented groups.

Drs Janet Deane, Andrew Blagborough and Matthias Landgraf are co-ordinating Experience Postgrad Life Sciences, an 8-week, paid, residential internship programme which aims to help biological and biomedical sciences undergraduates - including those studying medicine and veterinary medicine - develop research skills, get lab experience, and discover what postgraduate study involves.

“This is aimed at students at universities that are not research intensive and cannot offer this type of opportunity in a lab,” Dr Landgraf said. “These are students who have faced really challenging circumstances and have still found a way to overcome these.

“Creativity and innovation thrive in an environment that is varied and diverse, where people from different backgrounds and with different skills come together. This programme is also about access to information, helping these students create their own networks of connections. It’s very clear that a lot of them haven’t grown up in an environment – of relatives and friends – where they can tap into knowledge around university applications and career choices around postgraduate study or research. That is what we can provide.”

The Cambridge laboratories that host the students – who will be housed by Fitzwilliam College free of charge - will stay in contact with them beyond the summer internship, to provide ongoing help as they complete their undergraduate degrees and seek to enter postgraduate education.

Meanwhile, SHARE, an online pilot programme run by the School of the Humanities and Social Sciences, is aimed at undergraduate social sciences students from backgrounds underrepresented at postgraduate level. Participants, who receive a bursary of £650, will be matched with a PhD student mentor and an academic staff mentor, who will support them during a two-week programme of live events and group discussions, offering research methods training plus guidance on writing research proposals and applying for funding.

Dr Kristine Black-Hawkins, Deputy Head of the School of the Humanities and Social Sciences, said: "Encouraging students from diverse backgrounds into postgraduate study in the social sciences is a key part of the School’s mission. I am delighted to support this pilot project. We hope the programme will be an exciting opportunity for participants to find out more about postgraduate research as well as offer advice to those who wish to go onto further study, whether at Cambridge or elsewhere."

In developing the University’s first widening participation strategy at postgraduate level, Dr Powlesland has already overseen a major mapping exercise to understand at a granular level where there is underrepresentation in the UK-domiciled postgraduate community at Cambridge. As well as – for the first time – capturing contextual information about new candidates’ individual circumstances on the University’s postgraduate applications forms, the work also involves building up a detailed picture of the types of Master’s and PhD students already applying to the University, and pinpointing pockets of underrepresentation across the University’s academic divisions and departments. With no UCAS equivalent providing a widely used central hub for postgraduate applications, Widening Participation data - beyond the statutory reporting requirements collected by HESA (including gender, age, disability status, ethnicity) – has not historically been readily accessible in the sector.

“Diversifying postgraduate study is a sector-wide challenge, but Cambridge is now forging a clear path that I hope could support change in the sector as a whole,” said Dr Powlesland. “There is a belief in some quarters that if you’ve done an undergraduate degree then any disadvantage you had in your education before then has been levelled out. However, across Higher Education there is an acknowledgement - supported by the recent sector-wide expert analyses - that things are not as fair as they should be.

“Academic results will still be the starting point for application to postgraduate study, but if you’ve achieved a so-called ‘good’ degree – usually a 2:1 or above - while you’ve had to, for example, work a part-time job, or if you’ve had caring responsibilities whilst you’ve studied, that’s an even more impressive achievement and it’s important that admissions officers know about it.”

Further information:

• Experience Postgrad Life Sciences is a paid internship for 15 students taking place 5 July-27 August. It is sponsored by the BBSRC and the Wellcome Trust and hosted by the School of the Biological Sciences (SBS) and the School of Clinical Medicine (SCM). Fitzwilliam College will house students free of charge.
• SHARE is offered free of charge, and includes:
  • Two weeks of research training, postgraduate research application preparation, and mentoring
  • A bursary of £650 for the two-week programme (19-30 July 2021), intended to allow participants to fully concentrate on the programme without the need for paid employment to support themselves.

SHARE is supported by:
School of Humanities and Social Sciences, University of Cambridge
ESRC Doctoral Training Partnership for Social Sciences

This is to coincide with the Home Office’s publication of Great Britain’s statistics for animals used in research in 2020.

These ten organisations carried out 1,343,893 procedures, 47% or nearly half of the 2,883,310 procedures carried out in Great Britain in 2020. More than 99% of these 1,343,893 procedures were carried out in rodents or fish.

The statistics are freely available on the organisations’ websites as part of their ongoing commitment to transparency and openness around the use of animals in research.

The ten organisations are listed below alongside the total number of procedures that they carried out in 2020. This is the sixth consecutive year organisations have come together to publicise their collective statistics and examples of their research.

A further breakdown of Cambridge’s numbers, including the number of procedures by species and detail of the levels of severity, can be found on our animal research pages.

Animal research has been essential for developing lifesaving vaccines and treatments for Covid-19. Ferrets and macaque monkeys were used to test the safety and efficacy of Covid-19 vaccines, including the successful Oxford / AstraZeneca vaccine. Hamsters are being used to develop Covid-19 treatment strategies as they display a more severe form of the disease than ferrets and monkeys. Guinea pigs have also been used in regulatory research to batch test vaccine potency.

Despite all this research to develop vaccines and treatments for Covid-19, the majority of UK research facilities carried out significantly less research than usual due to the various national lockdowns. Therefore, the 2020 figures cannot be reasonably compared with previous statistics.

All organisations are committed to the ‘3Rs’ of replacement, reduction and refinement. This means avoiding or replacing the use of animals where possible; minimising the number of animals used per experiment and optimising the experience of the animals to improve animal welfare. However, as institutions expand and conduct more research, the total number of animals used can rise even if fewer animals are used per study.

All organisations listed are signatories to the Concordat on Openness on Animal Research in the UK, a commitment to be more open about the use of animals in scientific, medical and veterinary research in the UK. More than 120 organisations have signed the Concordat including UK universities, medical research charities, research funders, learned societies and commercial research organisations.

Wendy Jarrett, Chief Executive of Understanding Animal Research, which developed the Concordat on Openness, said:

"Animal research has been essential to the development and safety testing of lifesaving COVID-19 vaccines and treatments. Macaque monkeys and ferrets have been used to develop vaccines, including the Oxford / AstraZeneca vaccine, hamsters are being used to develop treatments, and guinea pigs are used to quality-check each batch of vaccines.

"Animal testing provided scientists with initial data that the vaccines were effective and safe enough to move into human clinical trials. During these trials, thousands more humans than animals were used to test how effective and safe the vaccines were in people. The pandemic has led to increased public interest in the way vaccines and medicines are developed and UAR has worked with research institutions and funding bodies throughout the UK to develop resources that explain to the public how animals have been used in this critical research."

University of Cambridge Establishment Licence Holder Dr Martin Vinnell said:

“Animal research currently plays an essential role in our understanding of health and disease and in the development of modern medicines and surgical techniques. Without the use of animals, we would not have many of the modern medicines, antibiotics, vaccines and surgical techniques we take for granted in both human and veterinary medicine.

“We always aim to use as few animals as possible, refining our research and actively looking for ways of replacing their use, for example in the development of ‘mini-organs’ grown from human cells, which can be used to model disease.”

Adapted from a press release by Understanding Animal Research.

Find out more

A team in the University of Cambridge’s Department of Engineering is developing implantable devices to bypass nerve damage and restore movement to paralysed limbs.

“Our aim is to make muscles wireless by intercepting electrical signals from the brain before they enter the damaged nerve and sending them directly to the target muscles via radio waves,” says Sam Hilton, a Research Assistant in the team.

The procedure has been tested and refined in computer simulations, and on cells grown in the lab. But before it can be tested in humans there is another important step: testing its safety in living rats. To avoid testing in animals entirely would place untenable risk on the first human recipients of this new device. All the experiments are carefully designed to ensure that just enough animals are used to produce convincing data, without resulting in unnecessary excess.

By working out how complex microelectronics can interface with living tissue in a very precise and controlled way, this work has potential to improve or restore movement in patients suffering severe nerve damage - improving their quality of life and easing the burden on our healthcare services.

The roadmap sets out a clear plan to create a bridge between two of Cambridge’s historical strengths — biomedical research and cutting-edge technology — and bring these specialisms together to develop new treatments and health tech with real world applications. The solutions in the roadmap are scalable beyond Cambridge and also applicable to other disciplines and sectors.

Professor Andy Neely, Pro-Vice-Chancellor for Enterprise and Business Relations at the University of Cambridge, said: “Cambridge has a deep and rich history of discovery and collaboration, and its interdisciplinary environment is the perfect testbed for new models of innovation in the life sciences. Our roadmap sets out a plan to do just that and will ensure that Cambridge remains a global leader in health technology into the next generation.

“This will require us to pioneer new ways of working and creating connections between different institutions across disciplines, be they academic or private enterprise. Such a model has been proven to work at a small scale – our proposal in the roadmap is to scale this up and apply it across the cluster and beyond.”

The University sits at the heart of the so-called ‘Cambridge cluster’, in which more than 5,300 knowledge-intensive firms employ more than 67,000 people and generate £18 billion in turnover. Cambridge has the highest number of patent applications per 100,000 residents in the UK.

The mission of the University is to contribute to society through the pursuit of education, learning and research at the highest international levels of excellence. This includes cultivating and delivering excellent research and world-leading innovation and training of the next generation of highly skilled researchers and entrepreneurs, thereby underpinning the UK's economic growth and competitiveness.

Professor Tony Kouzarides, Director of the Milner Therapeutics Institute at the University of Cambridge, said: “The pandemic has clearly shown the importance of rapid innovation in healthcare. We are determined to harness the power of innovation, creativity and collaboration in Cambridge, and apply this towards solving some of the biggest medical challenges facing the country, and the world.”

The Connect: Health Tech roadmap is a result of consultation with major stakeholders and a series of road-mapping workshops with the Cambridge community. It aims to shape the future success of the Cambridge cluster in health tech through a supportive and dynamic ecosystem that aligns with the needs of the community.

The roadmap includes ambitious steps to build strong foundations for the Cambridge cluster for the next 20 years and will support the region's economic recovery post-pandemic and bring cutting-edge research, businesses and innovators together to be better prepared and connected for the future. Connect: Health Tech will also increase access to the Cambridge ecosystem extending reach and helping to level up growth and investment across the East of England and the Oxford-Cambridge Arc.

One of the major recommendations in the report is to create and foster connectivity at the interface between medicine and technology and across sectors. This recommendation has been piloted by expanding the Cambridge cluster from a physical community to a digital one.

The COVID19 pandemic has required the creation of an innovative model of access and navigation to Cambridge. The digital platform simplifies navigation of the Cambridge research community and enables new companies based all over the world to access expertise and knowledge across the University with the aim of increasing inward investment in the life sciences. It also pilots an approach to navigation and connectivity that can be scaled up across the Arc and the UK. This new way of working will speed up the development of new healthcare innovations and technologies that the NHS will use in years to come.

Connect: Health Tech is a Cambridge University initiative funded by Research England. Connect: Health Tech UEZ has been created to build a highly effective interdisciplinary bridge between two Cambridge research hubs and beyond: the West science and technology hub anchored at the Maxwell Centre and South biomedical hub anchored at the Milner Therapeutics Institute. The bridge will bring together and integrate a community from across the University, research institutes, NHS, industry, investors, local and national Government, with a focus on medtech, digital health and therapeutics, to create opportunities that will transform ideas at the interface between medicine and technology into reality.

Read Creating a University Enterprise Zone for Cambridge across the life and physical sciences

The team has received funding from the National Institute for Health Research to develop a test that could complement existing antibody tests. They also aim to use similar biological signatures to develop a test and monitor for long COVID.

While most people recover from COVID-19 in a matter of days or weeks, around one in ten people go on to develop symptoms that can last for several months. This can be the case irrespective of the severity of their COVID-19 – even individuals who were asymptomatic can experience so-called ‘long COVID’.

Diagnosing long COVID can be a challenge, however. A patient with asymptomatic or mild disease may not have taken a PCR test at the time of infection – the gold standard for diagnosing COVID-19 –  and so has never had a confirmed diagnosis.  Even antibody tests – which look for immune cells produced in response to infection – are estimated to miss around 30% of cases, particularly among those who have had only mild disease and or beyond six months post-initial illness.

A team at the University of Cambridge and Cambridge University Hospital NHS Foundation Trust has received £370,000 from the National Institute for Health Research to develop a COVID-19 diagnostic test that would complement existing antibody tests and a test that could objectively diagnose and monitor long COVID.

The research builds on a pilot project supported by the Addenbrooke’s Charitable Trust. The team has been recruiting patients from the Long COVID Clinic established in May 2020 at Addenbrooke’s Hospital, part of Cambridge University Hospital NHS Foundation Trust.

During the pilot, the team recruited 85 patients to the Cambridge NIHR COVID BioResource, which collects blood samples from patients when they are first diagnosed and then at follow-up intervals over several months. They now hope to expand their cohort to 500 patients, recruited from Cambridgeshire and Peterborough.

In their initial findings, the team identified a biomarker – a biological fingerprint – in the blood of patients who had previously had COVID-19. This biomarker is a molecule known as a cytokine produced by T cells in response to infection. As with antibodies, this biomarker persists in the blood for a long time after infection. The team plans to publish their results shortly.

Dr Mark Wills from the Department of Medicine at the University of Cambridge, who co-leads the team, said: “We need a reliable and objective way of saying whether someone has had COVID-19. Antibodies are one sign we look for, but not everyone makes a very strong response and this can wane over time and become undetectable.

“We’ve identified a cytokine that is also produced in response to infection by T cells and is likely to be detectable for several months – and potentially years – following infection. We believe this will help us develop a much more reliable diagnostic for those individuals who did not get a diagnosis at the time of infection.”

By following patients for up to 18 months post-infection, the team hopes to address several questions, including whether immunity wanes over time. This will be an important part of helping understand whether people who have been vaccinated will need to receive boosters to keep them protected.

As part of their pilot study, the team also identified a particular biomarker found in patients with long COVID. Their work suggests these patients produce a second type of cytokine, which persists in patients with long COVID compared to those that recover quickly and might be one of the drivers behind the many symptoms that patients experience. This might therefore prove to be useful for diagnosing long COVID.

Dr Nyarie Sithole, also from the Department of Medicine at the University of Cambridge, who co-leads the team and helps to manage long COVID patients, said:  “Because we currently have no reliable way of diagnosing long COVID, the uncertainty can cause added stress to people who are experiencing potential symptoms. If we can say to them ‘yes, you have a biomarker and so you have long COVID’, we believe this will help allay some of their fears and anxieties.

“There is anecdotal evidence that patients see an improvement in symptoms of long COVID once they have been vaccinated – something that we have seen in a small number of patients in our clinic. Our study will allow us to see how this biomarker changes over a longer period of time in response to vaccination.”

At the moment, the team is using the tests for research purposes, but by increasing the size of their study cohort and carrying out further work, they hope to adapt and optimise the tests that can be scaled up and speeded up, able to be used by clinical diagnostic labs.

As well as developing a reliable test, the researchers hope their work will help provide an in-depth understanding of how the immune system responds to coronavirus infection – and why it triggers long COVID in some people.

Dr Sithole added: “One of the theories of what’s driving long COVID is that it’s a hyperactive immune response – in other words, the immune system switches on at the initial infection and for some reason never switches off or never goes back to the baseline. As we’ll be following our patients for many months post-infection, we hope to better understand whether this is indeed the case.”

In addition, having a reliable biomarker could help in the development of new treatments against COVID. Clinical trials require an objective measure of whether a drug is effective. Changes in – or the disappearance of – long-COVID-related cytokine biomarkers with corresponding symptom improvement in response to drug treatment would suggest that a treatment intervention is working.

Spending on pre-primary education accounts for less than 1% of the international community’s aid to education – equivalent to just 34 cents per child, per year – according to analysis by Cambridge University academics for Theirworld, the global children’s charity.

Research shows that pre-primary education is crucial to a child's development and that children who miss out fall behind even before they start primary school. Children enrolled in at least one year of pre-primary education are more likely to develop critical skills and are less likely to drop out of school.

Yet spending on pre-primary education remains consistently low, with donors on average committing 37 times more to post-secondary education, the analysis shows.

Of the world’s top 30 donors to education, eight do not spend a single cent on pre-primary education, including the Netherlands, Qatar, Sweden and Saudi Arabia.

The US, France, Denmark and Germany are among the 16 countries that commit less than 0.5% of their education aid budget to pre-primary education. The UK devotes 1.1%, closely behind Italy (1.8%), Belgium (1.9%), the Czech Republic and South Korea (2.2%).

Of all donor countries, only UNICEF and the Global Partnership for Education, one of the major funds for education in lower-income countries, meet Theirworld’s recommended target of investing at least 10% education aid budgets in pre-primary education. They are followed by Education Cannot Wait, a dedicated fund for crisis situations (8.6%), and New Zealand (6.7%). The World Bank is next, but some way behind (3.8%).

The report - A Better Start? - A Progress Check on Donor Funding for Pre-primary Education and Early Childhood Development - analyses data submitted by international donors to the OECD’s Development Assistance Committee Creditor Reporting System. The most up to date figures are from 2019 so reflect investment before the Covid-19 pandemic.

The analysis shows that the proportion of aid spent on pre-primary education has been increasing - but from a very low base, increasing between 2015 and 2019 from just 0.8% to 0.9%, the highest level since records began.

The report concludes that 6.4 million more children a year in low-income countries would benefit from pre-primary education if donors stepped up and met Theirworld’s recommended 10% target.

Investing in pre-primary education pays off. According to one estimate, for every dollar put into early childhood care and education, world leaders can expect a dividend of $17 in return.

Professor Pauline Rose, director of the Research for Equitable Access and Learning (REAL) Centre, University of Cambridge, and one of the report’s authors, said international donors need to wake up.

“The first five years of a child’s life are among the most critical for their long-term development and the benefits of investing in pre-primary education are found to be the greatest for the most disadvantaged,” she said.

“It is nothing short of a tragedy that world leaders are failing to prioritise spending in this area. The international community must wake up and step up. Without urgent action, the risk is that some of the world’s poorest and most marginalised will continue to fall behind.”

Sarah Brown, Chair of Theirworld, said: “Covid-19 has exacerbated the global education crisis and pushed the world’s poorest children further to the margins. We cannot let this continue.

“Over the next 12 months, world leaders have a series of opportunities at high level meetings, where global stimulus plans will be developed, to show their commitment to the provision of quality pre-primary education.”

Justin van Fleet, President of Theirworld, said: "We know that funding pre-primary education is the most important and impactful thing world leaders can do to give children around the world the best start in life and to put economies back on track following the pandemic.

“Thanks in part to our campaigning, progress has been made - but it’s not enough. It’s time for world leaders to walk the walk and invest 10% of their education aid budgets to the early years. Anything less is a failure for the world's children.”

Around four out of five people in the UK are thought to be infected with HCMV, and in developing countries this can be as high as 95%. For the majority of people, the virus remains dormant, hidden away inside white blood cells, where it can remain undisturbed and undetected for decades. If the virus reactivates in a healthy individual, it does not usually cause symptoms. However, for people who are immunocompromised – for example, transplant recipients who need to take immunosuppressant drugs to prevent organ rejection – HCMV reactivation can be devastating.

At present, there is no effective vaccine against HCMV, and anti-viral drugs often prove ineffective or have very serious side-effects.

Now, in a study published in Nature Communications, researchers at Vrije Universiteit Amsterdam in the Netherlands and at the University of Cambridge have found a way to chase the virus from its hiding place using a special type of antibody known as a nanobody.

Nanobodies were first identified in camels and exist in all camelids – a family of animals that also includes dromedary, llamas and alpacas. Human antibodies consist of two heavy and two light chains of molecules, which together recognise and bind to markers on the surface of a cell or virus known as antigens. For this special class of camelid antibodies, however, only a single fragment of the antibody – often referred to as single domain antibody or nanobody – is sufficient to properly recognize antigens.

Dr Timo De Groof from Vrije Universiteit Amsterdam, the study’s joint first author, said: “As the name suggests, nanobodies are much smaller than regular antibodies, which make them perfectly suited for particular types of antigens and relatively easy to manufacture and adjust. That’s why they’re being hailed as having the potential to revolutionise antibody therapies.”

The first nanobody has been approved and introduced onto the market by biopharmaceutical company Ablynx, while other nanobodies are already in clinical trials for diseases like rheumatoid arthritis and certain cancers. Now, the team in The Netherlands and the UK have developed nanobodies that target a specific virus protein (US28), one of the few elements detectable on the surface of a HCMV latently infected cell and a main driver of this latent state.

Dr Ian Groves from the Department of Medicine at the University of Cambridge said: “Our team has shown that nanobodies derived from llamas have the potential to outwit human cytomegalovirus. This could be very important as the virus can cause life-threatening complications in people whose immune systems are not functioning properly.”

In laboratory experiments using blood infected with the virus, the team showed that the nanobody binds to the US28 protein and interrupts the signals established through the protein that help keep the virus in its dormant state. Once this control is broken, the local immune cells are able to 'see' that the cell is infected, enabling the host’s immune cells to hunt down and kill the virus, purging the latent reservoir and clearing the blood of the virus.

Dr Elizabeth Elder, joint first author, who carried out her work while at the University of Cambridge, said: “The beauty of this approach is that it reactivates the virus just enough to make it visible to the immune system, but not enough for it to do what a virus normally does – replicating and spreading. The virus is forced to put its head above the parapet where it can then be killed by the immune system.”

Professor Martine Smit, also from from the Vrije Universiteit Amsterdam, added: “We believe our approach could lead to a much-needed new type of treatment for reducing – and potentially even preventing – CMV infectious in patients eligible for organ and stem cell transplants.”

The research was funded by the Dutch Research Council (NWO), Wellcome and the Medical Research Council, with support from the NIHR Cambridge Biomedical Research Centre.

Reference
De Groof TWM, Elder E, et al. Targeting the latent human cytomegalovirus reservoir for T-cell mediated killing with virus specific nanobodies. Nature Communications (2021). DOI: 10.1038/s41467-021-24608-5

In a study published in Molecular Psychiatry, the team show that changes in the extracellular matrix of the brain – ‘scaffolding’ around nerve cells – lead to loss of memory with ageing, but that it is possible to reverse these using genetic treatments.

Recent evidence has emerged of the role of perineuronal nets (PNNs) in neuroplasticity – the ability of the brain to learn and adapt – and to make memories. PNNs are cartilage-like structures that mostly surround inhibitory neurons in the brain. Their main function is to control the level of plasticity in the brain. They appear at around five years old in humans, and turn off the period of enhanced plasticity during which the connections in the brain are optimised. Then, plasticity is partially turned off, making the brain more efficient but less plastic.

PNNs contain compounds known as chondroitin sulphates. Some of these, such as chondroitin 4-sulphate, inhibit the action of the networks, inhibiting neuroplasticity; others, such as chondroitin 6-sulphate, promote neuroplasticity. As we age, the balance of these compounds changes, and as levels of chondroitin 6-sulphate decrease, so our ability to learn and form new memories changes, leading to age-related memory decline.

Researchers at the University of Cambridge and University of Leeds investigated whether manipulating the chondroitin sulphate composition of the PNNs might restore neuroplasticity and alleviate age-related memory deficits.

To do this, the team looked at 20-month old mice – considered very old – and using a suite of tests showed that the mice exhibited deficits in their memory compared to six-month old mice.

For example, one test involved seeing whether mice recognised an object. The mouse was placed at the start of a Y-shaped maze and left to explore two identical objects at the end of the two arms. After a short while, the mouse was once again placed in the maze, but this time one arm contained a new object, while the other contained a copy of the repeated object. The researchers measured the amount of time the mouse spent exploring each object to see whether it had remembered the object from the previous task. The older mice were much less likely to remember the object.

The team treated the ageing mice using a ‘viral vector’, a virus capable of reconstituting the amount of 6-sulphate chondroitin sulphates to the PNNs and found that this completely restored memory in the older mice, to a level similar to that seen in the younger mice.

Dr Jessica Kwok from the School of Biomedical Sciences at the University of Leeds said: “We saw remarkable results when we treated the ageing mice with this treatment. The memory and ability to learn were restored to levels they would not have seen since they were much younger.”

To explore the role of chondroitin 6-sulphate in memory loss, the researchers bred mice that had been genetically-manipulated such that they were only able to produce low levels of the compound to mimic the changes of ageing. Even at 11 weeks, these mice showed signs of premature memory loss. However, increasing levels of chondroitin 6-sulphate using the viral vector restored their memory and plasticity to levels similar to healthy mice.

Professor James Fawcett from the John van Geest Centre for Brain Repair at the University of Cambridge said: “What is exciting about this is that although our study was only in mice, the same mechanism should operate in humans – the molecules and structures in the human brain are the same as those in rodents. This suggests that it may be possible to prevent humans from developing memory loss in old age.”

The team have already identified a potential drug, licensed for human use, that can be taken by mouth and inhibits the formation of PNNs. When this compound is given to mice and rats it can restore memory in ageing and also improves recovery in spinal cord injury. The researchers are investigating whether it might help alleviate memory loss in animal models of Alzheimer's disease.

The approach taken by Professor Fawcett’s team – using viral vectors to deliver the treatment – is increasingly being used to treat human neurological conditions. A second team at the Centre recently published research showing their use for repairing damage caused by glaucoma and dementia.

The study was funded by Alzheimer’s Research UK, the Medical Research Council, European Research Council and the Czech Science Foundation.

Reference
Yang, S et al. Chondroitin 6-sulphate is required for neuroplasticity and memory in ageing. Molecular Psychiatry; 16 July 2021; DOI: doi.org/10.1038/s41380-021-01208-9

Researchers from the University of Cambridge have demonstrated how a typical touchscreen could be used to identify common ionic contaminants in soil or drinking water by dropping liquid samples on the screen, the first time this has been achieved. The sensitivity of the touchscreen sensor is comparable to typical lab-based equipment, which would make it useful in low-resource settings.

The researchers say their proof of concept could one day be expanded for a wide range of sensing applications, including for biosensing or medical diagnostics, right from the phone in your pocket. The results are reported in the journal Sensors and Actuators B.

Touchscreen technology is ubiquitous in our everyday lives: the screen on a typical smartphone is covered in a grid of electrodes, and when a finger disrupts the local electric field of these electrodes, the phone interprets the signal.

Other teams have used the computational power of a smartphone for sensing applications, but these have relied on the camera or peripheral devices, or have required significant changes to be made to the screen.

“We wanted to know if we could interact with the technology in a different way, without having to fundamentally change the screen,” said Dr Ronan Daly from Cambridge’s Institute of Manufacturing, who co-led the research. “Instead of interpreting a signal from your finger, what if we could get a touchscreen to read electrolytes, since these ions also interact with the electric fields?”

The researchers started with computer simulations, and then validated their simulations using a stripped down, standalone touchscreen, provided by two UK manufacturers, similar to those used in phones and tablets.

The researchers pipetted different liquids onto the screen to measure a change in capacitance and recorded the measurements from each droplet using the standard touchscreen testing software. Ions in the fluids all interact with the screen's electric fields differently depending on the concentration of ions and their charge.

“Our simulations showed where the electric field interacts with the fluid droplet. In our experiments, we then found a linear trend for a range of electrolytes measured on the touchscreen,” said first author Sebastian Horstmann, a PhD candidate at IfM. “The sensor saturates at an anion concentration of around 500 micromolar, which can be correlated to the conductivity measured alongside. This detection window is ideal to sense ionic contamination in drinking water.”

One early application for the technology could be to detect arsenic contamination in drinking water. Arsenic is another common contaminant found in groundwater in many parts of the world, but most municipal water systems screen for it and filter it out before it reaches a household tap. However, in parts of the world without water treatment plants, arsenic contamination is a serious problem.

“In theory, you could add a drop of water to your phone before you drink it, in order to check that it’s safe,” said Daly.

At the moment, the sensitivity of phone and tablet screens is tuned for fingers, but the researchers say the sensitivity could be changed in a certain part of the screen by modifying the electrode design in order to be optimised for sensing.

“The phone’s software would need to communicate with that part of the screen to deliver the optimum electric field and be more sensitive for the target ion, but this is achievable,” said Professor Lisa Hall from Cambridge’s Department of Chemical Engineering and Biotechnology, who co-led the research. “We’re keen to do much more on this – it’s just the first step.”

While it’s now possible to detect ions using a touchscreen, the researchers hope to further develop the technology so that it can detect a wide range of molecules. This could open up a huge range of potential health applications.

“For example, if we could get the sensitivity to a point where the touchscreen could detect heavy metals, it could be used to test for things like lead in drinking water. We also hope in the future to deliver sensors for home health monitoring,” said Daly.

“This is a starting point for broader exploration of the use of touchscreen sensing in mobile technologies and the creation of tools that are accessible to everyone, allowing rapid measurements and communication of data,” said Hall.

Reference:
Sebastian Horstmann, Cassi J Henderson, Elizabeth A H Hall, Ronan Daly ‘Capacitive touchscreen sensing - a measure of electrolyte conductivity.’ Sensors and Actuators B (2021). DOI: https://doi.org/10.1016/j.snb.2021.130318

This is the first time this vital, 400 million year old process has been visualised in real time in full root systems of living plants. Understanding the dynamics of plant colonisation by fungi could help to make food production more sustainable in the future.

Almost all crop plants form associations with a particular type of fungi – called arbuscular mycorrhiza fungi – in the soil, which greatly expand their root surface area. This mutually beneficial interaction boosts the plant’s ability to take up nutrients that are vital for growth. 

The more nutrients plants obtain naturally, the less artificial fertilisers are needed. Understanding this natural process, as the first step towards potentially enhancing it, is an ongoing research challenge. Progress is likely to pay huge dividends for agricultural productivity.

In a study published in the journal PLOS Biology, researchers used the bright red pigments of beetroot – called betalains – to visually track soil fungi as they colonised plant roots in a living plant. 

“We can now follow how the relationship between the fungi and plant root develops, in real-time, from the moment they come into contact. We previously had no idea about what happened because there was no way to visualise it in a living plant without the use of elaborate microscopy,” said Dr Sebastian Schornack, a researcher at the University of Cambridge’s Sainsbury Laboratory and joint senior author of the paper. 

To achieve their results, the researchers engineered two model plant species – a legume and a tobacco plant – so that they would produce the highly visible betalain pigments when arbuscular mycorrhiza fungi were present in their roots. This involved combining the control regions of two genes activated by mycorrhizal fungi with genes that synthesise red-coloured betalain pigments.

The plants were then grown in a transparent structure so that the root system was visible, and images of the roots could be taken with a flatbed scanner without disturbing the plants.

Using their technique, the researchers could select red pigmented parts of the root system to observe the fungus more closely as it entered individual plant cells and formed elaborate tree-like structures – called arbuscules – which grow inside the plant’s roots. Arbuscules take up nutrients from the soil that would otherwise be beyond the reach of the plant. 

Other methods exist to visualise this process, but these involve digging up and killing the plant and the use of chemicals or expensive microscopy. This work makes it possible for the first time to watch by eye and with simple imaging how symbiotic fungi start colonising living plant roots, and inhabit parts of the plant root system over time.

“This is an exciting new tool to visualise this, and other, important plant processes. Beetroot pigments are a distinctive colour, so they’re very easy to see. They also have the advantage of being natural plant pigments, so they are well tolerated by plants,” said Dr Sam Brockington, a researcher in the University of Cambridge’s Department of Plant Sciences, and joint senior author of the paper.

Mycorrhiza fungi are attracting growing interest in agriculture. This new technique provides the ability to ‘track and trace’ the presence of symbiotic fungi in soils from different sources and locations. The researchers say this will enable the selection of fungi that colonise plants fastest and provide the biggest benefits in agricultural scenarios.

Understanding and exploiting the dynamics of plant root system colonisation by fungi has potential to enhance future crop production in an environmentally sustainable way. If plants can take up more nutrients naturally, this will reduce the need for artificial fertilisers – saving money and reducing associated water pollution. 

This research was funded by the Biotechnology and Biological Sciences Research Council, Gatsby Charitable Foundation, Royal Society, and Natural Environment Research Council. 

Reference
Timoneda, A. & Yunusov, T. et al: ‘MycoRed: Betalain pigments enable in vivo real-time visualisation of arbuscular mycorrhizal colonisation.’ PLOS Biology, July 2021. DOI: 10.1371/journal.pbio.3001326