A single gene could be the reason why some of us carry an extra 30 pounds of fat
By the time they reach adulthood, they could be up to 30 pounds (13.6 kg) heavier with the excess weight likely to be mostly fat.
The NIHR Cambridge BRC-supported study found that when the MC4R gene does not work properly, our brains think we have lower fat stores than we do, signalling that we are starving and need to eat.
These results were found by studying the MC4R gene in a random sample of around 6,000 participants born in Bristol in 1990-91, who were recruited to Children of the 90s, a health study based at the University of Bristol.
Based on the frequency of mutations in this study, it is possible that around 200,000 people in the UK could carry a substantial amount of additional fat because of mutations in MC4R.
In the longer term, knowledge of the brain pathways controlled by MC4R should help in the design of drugs that bypass the signalling blockade and help restore people to a healthy weight.
This is an abridged version of the article first published on our website on 28 May 2021.
Repairing damaged donor livers course increase life-saving transplants
Bile ducts act as the liver’s waste disposal system, and malfunctioning bile ducts are responsible for a third of adult and 70 per cent of children’s liver transplantations.
Due to a shortage of livers, researchers needed to find alternative solutions and investigated whether they could repair the liver using cell-based therapies.
Using a perfusion system, researchers could show they could transplant biliary cells grown in the lab known as cholangiocytes organoids – in the bile duct that act as a barrier between the bile and other tissues – into damaged human livers to repair them.
In order to do this the researchers used a technique known as single-cell RNA sequencing to learn more about the individual cells lining the biliary tree. They found cells from the gallbladder could be converted into cells in the bile duct and could replace the damaged ones.
This is the first time a procedure of this kind has been used on human donor organs and could be useful for other organs.
Could diphtheria become a ‘major global threat’ again as it evolves?
Diphtheria is a highly contagious and potentially fatal infection yet it is easily preventable. Researchers have noticed as it evolves it is becoming resistant to a number of antibiotics.
In high-income countries, babies are vaccinated against infection. However, diphtheria is still problematic in low- and middle-income countries, where the disease can still cause infections in those who are unvaccinated. The disease can be spread through coughs, sneezes or close contact with someone who has been infected. Antibiotics is still the main method to treat the disease.
Researchers analysed the genomes of 61 bacteria isolated from patients and combining these with 441 publicly available genomes, the researchers were able to build a phylogenetic tree – a genetic ‘family tree’ – to see how the infections are related and understand how they spread. They also used this information to assess the presence of antimicrobial resistance (AMR) genes and assess toxin variation.
When the team looked for genes that might identify any resistance to antimicrobials, they found that the average number of AMR genes per genome was increasing each decade. Genomes of bacteria isolated from infections from the most recent decade (2010-19) showed the highest average number of AMR genes per genome, almost four times as many on average than in the next highest decade, the 1990s.
Read the full press release from 8 March 2021
How is research helping with life-saving liver transplants?
Professor Vallier explains that no donated livers are wasted even if they are not suitable for transplantation as researchers can use them to learn more about the liver and improve treatments to ultimately benefit patients.
Watch the short video below to find out about the latest research happening in Cambridge.
Cambridge GPs launch ‘pill on a string’ cancer check
The cytosponge or ‘pill on a string’ has been designed to help detect the early stages of oesophageal cancer.
Developed by the University of Cambridge and supported by the NIHR Cambridge BRC and NIHR Cambridge Clinical Research Facility, the device is now being trialled with GP patients in a mobile unit, known as the Heartburn Sponge Test unit. After Cambridge it will move on to Essex and then Suffolk as the pilot aims at proving a wider benefit to the NHS.
The hope is this new, quick and potentially life-saving device will detect the early signs of oesophageal cancer and treatment can begin a lot sooner.
The cytosponge is a small pill with a thread attached that the patient swallows, which expands into a small sponge when it reaches the stomach.
It is quickly pulled back up the throat by a nurse, collecting cells from the oesophagus which will be sent for analysis.
The procedure takes around 10 minutes and can be performed in a GP surgery.
Because oesophageal cancer is often found late, it is usually fatal. Only 17% of people diagnosed with it live for a further five years or more after diagnosis.
It is hoped the cytosponge could one day become a test used by GP surgeries throughout the country to identify potential issues for people who are on long-term heartburn medication, or when someone has had heartburn or indigestion for three weeks or more.
This is an abridged version of the article first published on our website on 17 June 2021.
Stress does not lead to loss of self-control in eating disorders
Cambridge researchers investigated whether binge-eating is caused by stress. They invited women with anorexia nervosa, bulimia nervosa and healthy controls to attend a study.
In a monitored environment women would receive controlled meals provided by a metabolic nutritionist. The women then underwent a fasting period during which they performed tasks whilst they received an MRI scan so researchers could look at their brain activity. The women also performed tasks to increase their stress levels, which was repeated.
After the tasks were completed the women were then offered an ‘all you can eat’ buffet in a relaxing environment and were told they could eat as much or as little as they would like.
On the second day of their study, the volunteers carried out the same tasks, but without the added stress.
The team found that even when the participants were not stressed, the women with bulimia nervosa performed worse on the main task, but this was not the case for those women affected by anorexia nervosa.
The researchers also found stress did not affect the actual performance in any way for either of the patient groups or the controls. However, the patient groups showed some differences in brain activity when they were stressed – and this activity differed between women with anorexia and those with bulimia.
While the researchers observed that the patients in general ate less in the buffet than the controls, the amount that they ate did not differ between the stress and control days.
The researchers also found when they were stressed, people with anorexia nervosa produce more of the hunger hormone, but contradictorily also more of a hormone that should tell them that they are full, so their bodies are sending them confusing signals about what to do around food.
People with bulimia nervosa had lower levels of cortisol, the ‘stress hormone’, than in healthy volunteers.
Read the full story published on 19 April 2021.
New gene variants identified that cause hypertension in pregnant women
Hypertension (high blood pressure) affects 30% of adults, who may then need long-term treatment to help prevent strokes and heart attacks.
For one in 10 of these patients, their hypertension is caused by a tiny benign nodule in one of the adrenals. These are glands near the kidneys that produce steroid hormones, including aldosterone that stimulates the kidneys to retain salt and hence increase blood pressure.
The research team found a number of gene variants which cause the production of high levels of aldosterone from small adrenal nodules, including a unique pair of new variants which always occur together. Patients in this group are mainly women, who present with sudden onset of high blood pressure and low blood potassium in the early months of a pregnancy.
Once the cause of the women’s hypertension was identified, they were able to complete a successful pregnancy and after birth had their adrenal nodule removed, curing their hypertension completely and meaning they could stop all their drugs.
This is an abridged version of the article first published on our website on 13 August 2021.
World first for AI and machine learning to treat Covid patients worldwide
In what’s known as federated learning, the research applied an algorithm to analyse anonymised electronic patient health data and chest x-rays from 10,000 Covid patients worldwide, including 250 at Addenbrooke’s Hospital.
The study – dubbed EXAM – took just two weeks of AI ‘learning’ to achieve high-quality predictions on how much extra oxygen a patient would need in the first days of hospital care.
To maintain strict patient confidentiality, the patient data was fully anonymised and an algorithm was sent to each hospital so no data was shared or left its location.
Once the algorithm had ‘learned’ from the data, the analysis was brought together to build an AI tool which could predict the oxygen needs of hospital Covid patients anywhere in the world.
This model can be used to help frontline physicians worldwide.
This is an abridged version of the article first published on our website on 15 September 2021.
Cambridge Clinical Vision Laboratory (CCVL)
The CCVL is a dedicated facility for vision research embedded within the NIHR Cambridge Clinical Research Facility in a strategic location next to the Early Phase Trials Unit.
The CCVL is part of a major drive by the NIHR Cambridge BRC to fast-track advanced gene therapy and cell-based therapies for ocular and neurodegenerative diseases. We also support early-phase experimental trials exploring novel chemotherapeutic and immunomodulatory agents for cancer and various autoimmune diseases.
The CCVL is available to assist and support your studies, including grant applications. Please contact us to discuss your ideas and requirements further.
Updated risk model helps doctors predict and prevent cardiovascular disease
The original risk model – SCORE (Systematic COronary Risk Evaluation) – was focused solely on predicting and preventing mortality, using data from the 1980s.
But now more people survive heart attacks and strokes than die from them, especially younger people, so the researchers wanted to show the absolute risk scores of people having non-fatal as well as fatal CVD within 10 years, using data from dozens of countries.
This updated model – SCORE2 – looked at data from 700,000 mainly middle-aged participants to develop risk prediction models tailored for use in European countries.
SCORE2 has been adopted by the European Guidelines on CVD Prevention in Clinical Practice.
This is an abridged version of the article first published on our website on 15 August 2021.
‘Biological fingerprint’ in blood could help identify COVID patients with no symptoms
This means they can identify people who have had COVID-19 even if they displayed no symptoms – and the biomarkers last several months after infection.
Current practice requires people to take a PCR test at the time of infection or an antibody test, to see if they had the virus but were asymptomatic.
As a result of the research the team has received £370,000 from the National Institute for Health Research (NIHR) to develop a COVID-19 diagnostic test that will complement existing antibody tests, as well as develop a test that could diagnose and monitor long Covid.
The research builds on a pilot project supported by the Addenbrooke’s Charitable Trust which has been recruiting patients from the Long COVID Clinic established in May 2020 at Addenbrooke’s Hospital.
During the pilot, the team recruited 85 patients to the Cambridge-led NIHR COVID BioResource, which collects blood samples from patients when they are first diagnosed and then at follow-up intervals over several months.
In their initial findings, they identified a molecule known as a cytokine produced by T cells in response to infection – which persists in the blood for a long time after 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 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 and might be useful for diagnosing long COVID and help in the development of new treatments against COVID.
This is an abridged version of the press release which was first published on our website on July 19, 2021.
Key mutations in Alpha variant enable SARS-CoV-2 to overcome evolutionary weak points
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 cells in our body, where the virus then replicates and spreads.
But as it divides and replicates, it also mutates. Some mutations make the virus 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 immuno-compromised patient treated with convalescent plasma (where the patient received blood plasma which already had antibodies). In particular, they saw the emergence of a key mutation – the deletion of two amino acids, H69/V70.
This deletion has since been seen across much of Europe, Africa and Asia – the so-called ‘Alpha’ variant – and appears to have spread multiple times independently.
Working under secure conditions, Professor Gupta and colleagues used a ‘pseudotype virus’ to understand how the spike protein interacts with host cells and what makes this mutation so important.
They found that the deletion makes the virus twice as infectiv – that is, the variants were both better at escaping immunity and more infectious.
This is an abridged version of the press release which was first published on our website on June 29, 2021.
From mother to baby; how mother’s metabolism determines the baby’s metabolism through the milk composition
One of the major components of breastmilk is fat, which is produced in the breast by the mammary gland, mainly from carbohydrates through a process called denovo lipogenesis, together with essential fatty acids from the circulations. The fat in the milk is metabolised by the infant and then brought into the circulation in a range of lipids.
We used high resolution mass spectrometry to study the fat composition of breastmilk from 30 mothers in the Gambia, as well as the lipid composition of the mother’s and infant’s blood, all at the same day, 3 months after birth. This gave us, for the first time, an insight how the metabolism from the mother affects the lipid metabolism of the infant, through the fat composition of the milk. Our results show that the fats produced in the breast are important for a health development of the infant.
Furse, S., Billing, G., Snowden, S. G., Smith, J., Goldberg, G., & Koulman, A. (2019). Relationship between the lipid composition of maternal plasma and infant plasma through breast milk. Metabolomics : Official journal of the Metabolomic Society,
Understanding the link between vitamin D and risk of type 2 diabetes
The number of people globally with type 2 diabetes continues to increase. There is an urgent need to find ways of preventing this serious condition.
Cambridge researchers established a collaboration with colleagues in 8 European countries to study the link between blood vitamin D markers (which show how much vitamin D a person has in their blood) and developing type 2 diabetes. They also forged a collaboration with a laboratory with technical expertise in the measurement of a number of different forms of blood vitamin D in the blood.
They found that higher levels of total vitamin D were related to having lower risk of type 2 diabetes but that some types of vitamin D can be associated with a risk of developing type 2 diabetes.
Their findings help to expand prior scientific knowledge as previous studies looked at the total amount of vitamin D diabetes patients had.
This research also helped researchers to understand whether people from northern and southern European countries had different levels (on average) of vitamin D, and the dietary sources that contribute to vitamin D levels in the blood.
This research provides the first evidence for differences in risk of type 2 diabetes depending on the specific type of blood vitamin D. It raises the importance of the need for further understanding of the biology of vitamin D when it is metabolised (processed) into different forms in the body. Further research will be needed to test if the links observed in this research point to cause and effect.
This case study relates to the publication by Zheng J et al. J Clin Endocrinol Metab 2019 Apr 1;104(4):1293-1303.
Reducing calories to improve pregnancy outcomes in gestational diabetes
Diabetes which first develops in pregnancy (gestational diabetes) affects around 5% of pregnant women in the UK. Gestational diabetes causes short term issues in pregnancy, such as increased fetal growth and increased birth-weight, but it is also associated with an increased long-term risk of type 2 diabetes for both mother and child. Current guidelines advise women diagnosed with gestational diabetes to change towards a healthier diet during pregnancy and to increase exercise levels. Such changes can often help control blood glucose (sugar) levels without medication. However, there is not a lot of evidence about the best diet for women with gestational diabetes.
Researchers from Cambridge are recruiting 500 women diagnosed with gestational diabetes for a dietary intervention study led by Dr Claire Meek, Senior Clinical Research Fellow at the Wellcome-MRC Institute of Metabolic Science. Participants will receive weekly home-delivered food boxes that contain all meals and snacks from 28 weeks pregnancy to when the baby is born. Women will be randomly allocated to receive either a standard calorie or a reduced calorie diet box.
The researchers are investigating the impact of the diet on the mother’s weight change in this period of pregnancy and on the baby’s birthweight. They are also making detailed measurements to investigate the impact of the diet on body fat changes. The mother’s usual diet will be measured before and after the diet box intervention using an online diet tool to record what they are eating and drinking (Intake24).
This innovative study, which is funded by Diabetes UK, will help to improve care for women with gestational diabetes and their babies in future.
Kusinski LC, Murphy HR, De Lucia Rolfe E, Rennie KL, Oude Griep LM, Hughes D, Taylor R, Meek CL. Dietary intervention in pregnant women with gestational diabetes: protocol for the DiGest Randomised Controlled Trial. Nutrients 2020, 12(4), 1165;
The NIHR identity
Download the local NIHR Cambridge BRC branding guidelines.
- For promotional materials (e.g. presentations) use your host institution’s templates. This will ensure you use their logo correctly.
- You may wish to include the logos of other organisations that have supported your research. These should all be the same size regardless of the value of their support. Where possible the NIHR organisation that has supported your research should go on the top left-hand side (but only if it is a leading partner). If more than one NIHR organisation has supported your research you should use the NIHR logo only and then refer to the individual parts (e.g. NIHR Cambridge BRC and NIHR Cambridge CRF) in your body copy.
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- NEVER stretch, manipulate or change the colour of any NIHR logo. The logos are available in full colour, black and white and transparent formats and should fit all your requirements. For more advice and to download the logos for web and print please contact the BRC comms team.
Templates for NIHR staff only:
If you represent the NIHR, did you know there are templates available that you can use for your posters, banners, presentations and reports?
If the material you are producing represents a collaboration between two or more NIHR organisations (e.g. NIHR Cambridge BRC and NIHR Cambridge CRF) you should use templates with the NIHR logo only and then refer to the individual parts of the NIHR in your body copy.
Please contact the BRC comms team to find out more, and also for links to download NIHR logos and brand identity guidelines.
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Please contact your organisation’s communications department for the required consent forms or contact cuh.brccomms@nhs.net.
The participant must also receive a copy for their records so they know who to get in touch with if they wish to withdraw their consent.
- Download the CUH consent form
Creating accessible documents
The NIHR Cambridge BRC has put together a guide on how to create documents that comply with accessibility requirements.
This contains information relevant to all researchers on how to make your documents accessible.
For NIHR staff there are also templates which you can download and adapt for your organisations.
Differing immune responses discovered in asymptomatic cases and those with severe COVID-19
In the study, researchers and their collaborators in the Human Cell Atlas initiative analysed blood from 130 people with COVID-19. These patients came from three different UK centres in Newcastle, Cambridge and London and ranged from asymptomatic to critically severe.
The researchers found raised levels of specific immune cells in asymptomatic people to help fight infection – but patients with more serious symptoms had lost these protective cell types and instead gained inflammatory cells. In severe cases this led to lung inflammation, blood clotting difficulties and hospitalisation.
While it is not yet understood how the infection stimulates these immune responses, the study gives a molecular explanation for how COVID-19 could cause an increased risk of blood clotting and inflammation in the lungs, which can lead to the patient needing a ventilator.
This also uncovers potential new therapeutic targets to help protect patients against inflammation and severe disease.
In the future, research may identify those who are more likely to experience moderate to severe disease by looking at levels of these immune cells in their blood.
This is an abridged version of the press release which was first published on our website on April 22, 2021.
Cambridge Enterprise
We help transform your ideas into commercial opportunities attractive to organisations that can bring them to market and support formation of new companies and social enterprises.
We also manage the commercial relationship and negotiation of relevant agreements. Our remit extends to supporting the development of intellectual property arising from NIHR Cambridge BRC activities and collaborations between the University of Cambridge and the NHS; if you are either a CUH NHS Trust employee, or a University employee supported by the NIHR Cambridge BRC, and want to discuss how to commercialise your technology, we have the experience and expertise to support you.
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If you would like to ask us a question, please email CBRCIPSupport@enterprise.cam.ac.uk, and someone from the team will get in touch with you.