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The event was an opportunity to showcase this impressive contribution to the UK economy to Parliamentarians and policy makers. It was also a chance to discuss how elements of Cambridge's strategic success may be implemented in new and emerging clusters across the UK.

A highlight of the evening was George Freeman MP, the current Minister of State for Science, Innovation and Technology, delivering a very well received speech on the importance of Cambridge as the "golden corner of the golden triangle". The Minister expressed his delight at receiving such a short, focused summary report and spoke of the importance of the continued success of Cambridge for both the East of England and wider UK economy. 

The Member of Parliament for Cambridge, Daniel Zeichner MP, offered thoughts on infrastructure issues in the city that, if solved, would unlock further potential for economic growth, including tackling congestion, seeing progress on East West Rail, and finding solutions to the lack of lab space. He also described how centres of excellence, like Cambridge, need to be nurtured and supported by government policy, including targeted funding to incentivise innovation. The report had immediate impact when Daniel mentioned the results of the analysis in the House of Commons budget debate that he returned to immediately after the event.

Baroness Sally Morgan of Huyton, Master at Fitzwilliam, and who kindly sponsored the event, highlighted the finding, that for every £1 the University spends, it creates £11.70 of economic impact.

Professor Andy Neely closed the speeches, restating the headline findings and highlighting the ways in which government policy could support the ecosystem’s continued success and help Cambridge attract the best global talent.  

We were delighted to host local stakeholders, including representatives from Nyobolt, Abcam and Cambridge Enterprise, who were on hand to answer questions on how and why the University was crucial to their success. 

Attendees from Parliament included former Universities Minister and Chair of Innovate Cambridge, Lord David Willetts and former Chancellor, Lord Norman Lamont. From the Commons, Chi Onwurah MP (Shadow Science Minister) and Seema Malhotra MP, also joined us for the event.

On Monday 20 March, the University of Cambridge hosted a reception in the Houses of Parliament to launch a new report that shows it is a research powerhouse driving the most successful economic cluster in the UK. The analysis by respected consultancy London Economics shows that the University adds nearly £30 billion to the economy every year and supports more than 86,000 jobs across the UK

The text in this work is licensed under a Creative Commons Attribution 4.0 International License. Images, including our videos, are Copyright ©University of Cambridge and licensors/contributors as identified.  All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

Yes

One Health In Action in the Caribbean

Chris is a Professor of Veterinary Virology at the School of Veterinary Medicine, University of the West Indies (UWI) in Trinidad and Tobago. He took up his post at the University of the West Indies in early 2012 and is currently running a One Health – based research programme. He has recently received the UWI Vice Chancellor award for research, is a member of the UWI Covid-19 taskforce and is a member of the World Organisation for Animal Health (WOAH) Biological Standards Commission.

Talk summary: Chris will talk about the work he has been doing promoting the One Health approach across the Caribbean region. There has been a growing consensus that a One Health approach is necessary to address many of the health and development issues of today. His presentation will outline actions being taken to roll out the One Health approach to health challenges faced within the Caribbean, emphasizing the importance of collaboration and building partnerships. The presentation will describe two European Union funded projects that Chris has led. The “One Health One Caribbean One Love” and ‘Climate Change and One Health’ projects are example of ‘One Health in Action’. Both project are developing cohorts / networks of Caribbean professionals with the knowledge and skills to become change agents in their respective fields.

Chaired by Professor James Wood

• Speaker: Professor Chris Oura, School of Veterinary Medicine, University of the West Indies
• Thursday 11 May 2023, 16:00-17:00
• Venue: LT2.
• Series: Departmental Seminar Programme, Department of Veterinary Medicine; organiser: Fiona Roby.

Add to your calendar or Include in your list

One Health In Action in the Caribbean

Chris is a Professor of Veterinary Virology at the School of Veterinary Medicine, University of the West Indies (UWI) in Trinidad and Tobago. He took up his post at the University of the West Indies in early 2012 and is currently running a One Health – based research programme. He has recently received the UWI Vice Chancellor award for research, is a member of the UWI Covid-19 taskforce and is a member of the World Organisation for Animal Health (WOAH) Biological Standards Commission.

Talk summary: Chris will talk about the work he has been doing promoting the One Health approach across the Caribbean region. There has been a growing consensus that a One Health approach is necessary to address many of the health and development issues of today. His presentation will outline actions being taken to roll out the One Health approach to health challenges faced within the Caribbean, emphasizing the importance of collaboration and building partnerships. The presentation will describe two European Union funded projects that Chris has led. The “One Health One Caribbean One Love” and ‘Climate Change and One Health’ projects are example of ‘One Health in Action’. Both project are developing cohorts / networks of Caribbean professionals with the knowledge and skills to become change agents in their respective fields.

Chaired by Professor James Wood

• Speaker: Professor Chris Oura, School of Veterinary Medicine, University of the West Indies
• Thursday 11 May 2023, 16:00-17:00
• Venue: LT2.
• Series: Departmental Seminar Programme, Department of Veterinary Medicine; organiser: Fiona Roby.

Add to your calendar or Include in your list

The first Innovate UK award, received in 2021, allowed SMi to partner with the Cambridge Institute of Therapeutic Immunology and Infectious Disease, the Medicines Discovery Catapult and the National Physical Laboratory to develop its technology for testing for respiratory diseases. The second award, made in early 2023, is helping SMi and its partners apply the same technology to detecting cancer.

Co-founded in 2018 by former University of Cambridge researcher Dr Andrew Thompson, SMi is developing a new technology that analyses samples using super-resolution imaging. The technology can detect, quantify and characterise single molecules that are of interest, including DNA, RNA and protein molecules associated with specific diseases. It can visualise what other technologies cannot see and very rapidly batch analyse hundreds of samples with extremely high accuracy.

The first round of £1.9m funding enabled SMi to develop its platform, used for the simultaneous screening of common respiratory diseases. The COVID-19 pandemic demonstrated the need for rapid and cost-effective diagnostic testing on a massive scale. Test accuracy and the ability to identify new variants were critical.

The second Innovate UK award has funded the application of SMi’s platform to cancer diagnosis by enabling work with another team of specialists at the Medicines Discovery Catapult. Here the same single molecule visualisation approach is being used to detect and quantify cancer biomarkers in patient blood samples. This will help clinicians to make more accurate assessments, and combined with the flexibility, accuracy, speed and high throughput of SMi’s technology, could reduce diagnostic backlogs and provide patients with their results much sooner.

SMi’s aim has always been to create a user-friendly, automated benchtop instrument that can be used in both research and healthcare settings. Initial instrument designs were guided by consultation with NHS trusts and the NIHR Medical Devices Testing and Evaluation Centre (MD-TEC), while prototypes have been tested in labs at the University of Cambridge, the Medicines Discovery Catapult and the National Physical Laboratory. Commercial production will be outsourced to a medical device manufacturer in the East of England.

SMi’s CEO Dr Andrew Thompson said: “SMi is creating a highly accurate and user-friendly platform that is based upon single molecule imaging, meaning that we can detect individual molecules that are invisible to other technologies. With an approach that allows them to reliably monitor single molecules, SMi provides scientists and clinicians with a quality of data that is unprecedented. Such capabilities are likely to have far-reaching benefits for diagnosis and the discovery of new medicines. Our Innovate UK funding is allowing us to work with very highly qualified research and clinical partners, providing a means to accelerate our product development and realise these opportunities sooner.”

The Cambridge Institute for Therapeutic Immunology and Infectious Diseases has been leading the University of Cambridge’s collaboration with SMi. Ravindra Gupta, Professor of Clinical Microbiology, and named as one of Time Magazine’s 100 most influential people of the year in 2020 for his work on HIV, said: “SMi’s platform is incredibly exciting and could revolutionise testing for a range of diseases. We have been fortunate to partner with SMi on SARS-CoV-2 detection, and application could extend to identification of specific genetic variants of pathogens as well as cancers.”

Dr Tammy Dougan, Life Science and Healthcare Partnership Lead in the University’s Strategic Partnerships Office, said: “This is a great example of a Cambridge start-up winning Innovate UK funding and using it to build effective collaborations between research partners to take a new technology out of the lab and into clinical practice.”

Since 2018, SMi has grown into a team of sixteen, including scientists, mechanical engineers, software engineers and medical device specialists based in two locations: the outskirts of Cambridge and the West Coast of the USA.

Cambridge start-up SMi and its research partners have received two Innovate UK awards to progress their work on testing for infectious diseases and detecting biomarkers for cancer.

Andrew Brookes, Getty Images: Pipetting sample into a tray

The text in this work is licensed under a Creative Commons Attribution 4.0 International License. Images, including our videos, are Copyright ©University of Cambridge and licensors/contributors as identified.  All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

Yes

The first Innovate UK award, received in 2021, allowed SMi to partner with the Cambridge Institute of Therapeutic Immunology and Infectious Disease, the Medicines Discovery Catapult and the National Physical Laboratory to develop its technology for testing for respiratory diseases. The second award, made in early 2023, is helping SMi and its partners apply the same technology to detecting cancer.

Co-founded in 2018 by former University of Cambridge researcher Dr Andrew Thompson, SMi is developing a new technology that analyses samples using super-resolution imaging. The technology can detect, quantify and characterise single molecules that are of interest, including DNA, RNA and protein molecules associated with specific diseases. It can visualise what other technologies cannot see and very rapidly batch analyse hundreds of samples with extremely high accuracy.

The first round of £1.9m funding enabled SMi to develop its platform, used for the simultaneous screening of common respiratory diseases. The COVID-19 pandemic demonstrated the need for rapid and cost-effective diagnostic testing on a massive scale. Test accuracy and the ability to identify new variants were critical.

The second Innovate UK award has funded the application of SMi’s platform to cancer diagnosis by enabling work with another team of specialists at the Medicines Discovery Catapult. Here the same single molecule visualisation approach is being used to detect and quantify cancer biomarkers in patient blood samples. This will help clinicians to make more accurate assessments, and combined with the flexibility, accuracy, speed and high throughput of SMi’s technology, could reduce diagnostic backlogs and provide patients with their results much sooner.

SMi’s aim has always been to create a user-friendly, automated benchtop instrument that can be used in both research and healthcare settings. Initial instrument designs were guided by consultation with NHS trusts and the NIHR Medical Devices Testing and Evaluation Centre (MD-TEC), while prototypes have been tested in labs at the University of Cambridge, the Medicines Discovery Catapult and the National Physical Laboratory. Commercial production will be outsourced to a medical device manufacturer in the East of England.

SMi’s CEO Dr Andrew Thompson said: “SMi is creating a highly accurate and user-friendly platform that is based upon single molecule imaging, meaning that we can detect individual molecules that are invisible to other technologies. With an approach that allows them to reliably monitor single molecules, SMi provides scientists and clinicians with a quality of data that is unprecedented. Such capabilities are likely to have far-reaching benefits for diagnosis and the discovery of new medicines. Our Innovate UK funding is allowing us to work with very highly qualified research and clinical partners, providing a means to accelerate our product development and realise these opportunities sooner.”

The Cambridge Institute for Therapeutic Immunology and Infectious Diseases has been leading the University of Cambridge’s collaboration with SMi. Ravindra Gupta, Professor of Clinical Microbiology, and named as one of Time Magazine’s 100 most influential people of the year in 2020 for his work on HIV, said: “SMi’s platform is incredibly exciting and could revolutionise testing for a range of diseases. We have been fortunate to partner with SMi on SARS-CoV-2 detection, and application could extend to identification of specific genetic variants of pathogens as well as cancers.”

Dr Tammy Dougan, Life Science and Healthcare Partnership Lead in the University’s Strategic Partnerships Office, said: “This is a great example of a Cambridge start-up winning Innovate UK funding and using it to build effective collaborations between research partners to take a new technology out of the lab and into clinical practice.”

Since 2018, SMi has grown into a team of sixteen, including scientists, mechanical engineers, software engineers and medical device specialists based in two locations: the outskirts of Cambridge and the West Coast of the USA.

Cambridge start-up SMi and its research partners have received two Innovate UK awards to progress their work on testing for infectious diseases and detecting biomarkers for cancer.

Andrew Brookes, Getty Images: Pipetting sample into a tray

The text in this work is licensed under a Creative Commons Attribution 4.0 International License. Images, including our videos, are Copyright ©University of Cambridge and licensors/contributors as identified.  All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

Yes

The first Innovate UK award, received in 2021, allowed SMi to partner with the Cambridge Institute of Therapeutic Immunology and Infectious Disease, the Medicines Discovery Catapult and the National Physical Laboratory to develop its technology for testing for respiratory diseases. The second award, made in early 2023, is helping SMi and its partners apply the same technology to detecting cancer.

Co-founded in 2018 by former University of Cambridge researcher Dr Andrew Thompson, SMi is developing a new technology that analyses samples using super-resolution imaging. The technology can detect, quantify and characterise single molecules that are of interest, including DNA, RNA and protein molecules associated with specific diseases. It can visualise what other technologies cannot see and very rapidly batch analyse hundreds of samples with extremely high accuracy.

The first round of £1.9m funding enabled SMi to develop its platform, used for the simultaneous screening of common respiratory diseases. The COVID-19 pandemic demonstrated the need for rapid and cost-effective diagnostic testing on a massive scale. Test accuracy and the ability to identify new variants were critical.

The second Innovate UK award has funded the application of SMi’s platform to cancer diagnosis by enabling work with another team of specialists at the Medicines Discovery Catapult. Here the same single molecule visualisation approach is being used to detect and quantify cancer biomarkers in patient blood samples. This will help clinicians to make more accurate assessments, and combined with the flexibility, accuracy, speed and high throughput of SMi’s technology, could reduce diagnostic backlogs and provide patients with their results much sooner.

SMi’s aim has always been to create a user-friendly, automated benchtop instrument that can be used in both research and healthcare settings. Initial instrument designs were guided by consultation with NHS trusts and the NIHR Medical Devices Testing and Evaluation Centre (MD-TEC), while prototypes have been tested in labs at the University of Cambridge, the Medicines Discovery Catapult and the National Physical Laboratory. Commercial production will be outsourced to a medical device manufacturer in the East of England.

SMi’s CEO Dr Andrew Thompson said: “SMi is creating a highly accurate and user-friendly platform that is based upon single molecule imaging, meaning that we can detect individual molecules that are invisible to other technologies. With an approach that allows them to reliably monitor single molecules, SMi provides scientists and clinicians with a quality of data that is unprecedented. Such capabilities are likely to have far-reaching benefits for diagnosis and the discovery of new medicines. Our Innovate UK funding is allowing us to work with very highly qualified research and clinical partners, providing a means to accelerate our product development and realise these opportunities sooner.”

The Cambridge Institute for Therapeutic Immunology and Infectious Diseases has been leading the University of Cambridge’s collaboration with SMi. Ravindra Gupta, Professor of Clinical Microbiology, and named as one of Time Magazine’s 100 most influential people of the year in 2020 for his work on HIV, said: “SMi’s platform is incredibly exciting and could revolutionise testing for a range of diseases. We have been fortunate to partner with SMi on SARS-CoV-2 detection, and application could extend to identification of specific genetic variants of pathogens as well as cancers.”

Dr Tammy Dougan, Life Science and Healthcare Partnership Lead in the University’s Strategic Partnerships Office, said: “This is a great example of a Cambridge start-up winning Innovate UK funding and using it to build effective collaborations between research partners to take a new technology out of the lab and into clinical practice.”

Since 2018, SMi has grown into a team of sixteen, including scientists, mechanical engineers, software engineers and medical device specialists based in two locations: the outskirts of Cambridge and the West Coast of the USA.

Cambridge start-up SMi and its research partners have received two Innovate UK awards to progress their work on testing for infectious diseases and detecting biomarkers for cancer.

Andrew Brookes, Getty Images: Pipetting sample into a tray

The text in this work is licensed under a Creative Commons Attribution 4.0 International License. Images, including our videos, are Copyright ©University of Cambridge and licensors/contributors as identified.  All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

Yes

Scientists at the Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID) and Wellcome Sanger Institute showed that following SARS-CoV-2 infection, cells in the lining of the lungs, nasal cells, and immune cells in the blood show a blunted inflammatory response in obese patients, producing suboptimal levels of molecules needed to fight the infection.

Since the start of the pandemic, there have been almost 760 million confirmed cases of SARS-CoV-2 infection, with almost 6.9 million deaths. While some people have very mild – or even no – symptoms, others have much more severe symptoms, including acute respiratory distress syndrome requiring ventilator support.

One of the major risk factors for severe COVID-19 is obesity, which is defined as a body mass index (BMI) of over 30. More than 40% of US adults and 28% of adults in England are classed as obese.

While this link has been shown in numerous epidemiological studies, until now, it has not been clear why obesity should increase an individual’s risk of severe COVID-19. One possible explanation was thought to be that obesity is linked to inflammation: studies have shown that people who are obese already have higher levels of key molecules associated with inflammation in their blood. Could an overactive inflammatory response explain the connection?

Professor Menna Clatworthy is a clinician scientist at the University of Cambridge, studying tissue immune cells at CITIID alongside caring for patients at Addenbrooke’s Hospital, part of Cambridge University Hospitals NHS Foundation Trust. She said: “During the pandemic, the majority of younger patients I saw on the COVID wards were obese. Given what we know about obesity, if you’d asked me why this was the case, I would have said that it was most likely due to excessive inflammation. What we found was the absolute opposite.”

Clatworthy and her team analysed blood and lung samples taken from 13 obese patients with severe COVID-19 requiring mechanical ventilation and intensive care treatment, and 20 controls (non-obese COVID-19 patients and ventilated non-COVID-19 patients). These included patients admitted to the Intensive Care Unit at Addenbrooke’s Hospital.

Her team used a technique known as transcriptomics, which looks at RNA molecules produced by our DNA, to study activity of cells in these key tissues. Their results are published in the American Journal of Respiratory and Critical Care Medicine.

Contrary to expectations, the researchers found that the obese patients had underactive immune and inflammatory responses in their lungs.  In particular, when compared to non-obese patients, cells in the lining of their lungs and some of their immune cells had lower levels of activity among genes responsible for the production of two molecules known as interferons (INF) – interferon-alpha and interferon-gamma – which help control the response of the immune system, and of tumour necrosis factor (TNF), which causes inflammation.

When they looked at immune cells in the blood of 42 adults from an independent cohort, they found a similar, but less marked, reduction in the activity of interferon-producing genes as well as lower levels of IFN-alpha in the blood.

Professor Clatworthy said: “This was really surprising and unexpected. Across every cell type we looked at, we found that that the genes responsible for the classical antiviral response were less active. They were completely muted.”

The team was able to replicate its findings in nasal immune cells taken from obese children with COVID-19, where they again found lower levels of activity among the genes that produce IFN-alpha and IFN-gamma. This is important because the nose is one of the entry points for the virus – a robust immune response there could prevent the infection spreading further into the body, while a poorer response would be less effective.

One possible explanation for the finding involves leptin, a hormone produced in fat cells that controls appetite. Leptin also plays a role in the immune response: in individuals who are normal weight, levels of the hormone increase in response to infection and it directly stimulates immune cells. But obese people already have chronically higher levels of leptin, and Clatworthy says it is possible that they no longer produce sufficient additional leptin in response to infection, or are insensitive to it, leading to inadequate stimulation of their immune cells.

The findings could have important implications both for the treatment of COVID-19 and in the design of clinical trials to test new treatments.

Because an overactive immune and inflammatory response can be associated with severe COVID-19 in some patients, doctors have turned to anti-inflammatory drugs to dampen this response. But anti-inflammatory drugs may not be appropriate for obese patients.

Co-author Dr Andrew Conway Morris from the Department of Medicine at the University of Cambridge and Honorary Consultant on the intensive care unit at Addenbrooke’s Hospital said: “What we’ve shown is that not all patients are the same, so we might need to tailor treatments. Obese subjects might need less anti-inflammatory treatments and potentially more help for their immune system.”

Clinical trials for potential new treatments would need to involve stratifying patients rather than including both severe and normal weight patients, whose immune responses differ.

The research was largely supported by Wellcome, the Medical Research Council and the National Institute of Health and Care Research, including via the NIHR Cambridge Biomedical Research Centre.

Reference
Guo, SA, Bowyer, GS, Ferdinand, JR, Maes, M & Tuong, ZK et al. Obesity associated with attenuated tissue immune cell responses in COVID-19. Am J Resp Critical Care Med; 1 Mar 2023; DOI: 10.1164/rccm.202204-0751OC 

Individuals who are obese may be more susceptible to severe COVID-19 because of a poorer inflammatory immune response, say Cambridge scientists.

During the pandemic, the majority of younger patients I saw on the COVID wards were obese... I would have said that it was most likely due to excessive inflammation. What we found was the absolute oppositeMenna ClatworthyCambridge University Hospitals NHS Foundation TrustIntensive care unit at Addenbrooke's Hospital

The text in this work is licensed under a Creative Commons Attribution 4.0 International License. Images, including our videos, are Copyright ©University of Cambridge and licensors/contributors as identified.  All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

Yes

Scientists at the Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID) and Wellcome Sanger Institute showed that following SARS-CoV-2 infection, cells in the lining of the lungs, nasal cells, and immune cells in the blood show a blunted inflammatory response in obese patients, producing suboptimal levels of molecules needed to fight the infection.

Since the start of the pandemic, there have been almost 760 million confirmed cases of SARS-CoV-2 infection, with almost 6.9 million deaths. While some people have very mild – or even no – symptoms, others have much more severe symptoms, including acute respiratory distress syndrome requiring ventilator support.

One of the major risk factors for severe COVID-19 is obesity, which is defined as a body mass index (BMI) of over 30. More than 40% of US adults and 28% of adults in England are classed as obese.

While this link has been shown in numerous epidemiological studies, until now, it has not been clear why obesity should increase an individual’s risk of severe COVID-19. One possible explanation was thought to be that obesity is linked to inflammation: studies have shown that people who are obese already have higher levels of key molecules associated with inflammation in their blood. Could an overactive inflammatory response explain the connection?

Professor Menna Clatworthy is a clinician scientist at the University of Cambridge, studying tissue immune cells at CITIID alongside caring for patients at Addenbrooke’s Hospital, part of Cambridge University Hospitals NHS Foundation Trust. She said: “During the pandemic, the majority of younger patients I saw on the COVID wards were obese. Given what we know about obesity, if you’d asked me why this was the case, I would have said that it was most likely due to excessive inflammation. What we found was the absolute opposite.”

Clatworthy and her team analysed blood and lung samples taken from 13 obese patients with severe COVID-19 requiring mechanical ventilation and intensive care treatment, and 20 controls (non-obese COVID-19 patients and ventilated non-COVID-19 patients). These included patients admitted to the Intensive Care Unit at Addenbrooke’s Hospital.

Her team used a technique known as transcriptomics, which looks at RNA molecules produced by our DNA, to study activity of cells in these key tissues. Their results are published in the American Journal of Respiratory and Critical Care Medicine.

Contrary to expectations, the researchers found that the obese patients had underactive immune and inflammatory responses in their lungs.  In particular, when compared to non-obese patients, cells in the lining of their lungs and some of their immune cells had lower levels of activity among genes responsible for the production of two molecules known as interferons (INF) – interferon-alpha and interferon-gamma – which help control the response of the immune system, and of tumour necrosis factor (TNF), which causes inflammation.

When they looked at immune cells in the blood of 42 adults from an independent cohort, they found a similar, but less marked, reduction in the activity of interferon-producing genes as well as lower levels of IFN-alpha in the blood.

Professor Clatworthy said: “This was really surprising and unexpected. Across every cell type we looked at, we found that that the genes responsible for the classical antiviral response were less active. They were completely muted.”

The team was able to replicate its findings in nasal immune cells taken from obese children with COVID-19, where they again found lower levels of activity among the genes that produce IFN-alpha and IFN-gamma. This is important because the nose is one of the entry points for the virus – a robust immune response there could prevent the infection spreading further into the body, while a poorer response would be less effective.

One possible explanation for the finding involves leptin, a hormone produced in fat cells that controls appetite. Leptin also plays a role in the immune response: in individuals who are normal weight, levels of the hormone increase in response to infection and it directly stimulates immune cells. But obese people already have chronically higher levels of leptin, and Clatworthy says it is possible that they no longer produce sufficient additional leptin in response to infection, or are insensitive to it, leading to inadequate stimulation of their immune cells.

The findings could have important implications both for the treatment of COVID-19 and in the design of clinical trials to test new treatments.

Because an overactive immune and inflammatory response can be associated with severe COVID-19 in some patients, doctors have turned to anti-inflammatory drugs to dampen this response. But anti-inflammatory drugs may not be appropriate for obese patients.

Co-author Dr Andrew Conway Morris from the Department of Medicine at the University of Cambridge and Honorary Consultant on the intensive care unit at Addenbrooke’s Hospital said: “What we’ve shown is that not all patients are the same, so we might need to tailor treatments. Obese subjects might need less anti-inflammatory treatments and potentially more help for their immune system.”

Clinical trials for potential new treatments would need to involve stratifying patients rather than including both severe and normal weight patients, whose immune responses differ.

The research was largely supported by Wellcome, the Medical Research Council and the National Institute of Health and Care Research, including via the NIHR Cambridge Biomedical Research Centre.

Reference
Guo, SA, Bowyer, GS, Ferdinand, JR, Maes, M & Tuong, ZK et al. Obesity associated with attenuated tissue immune cell responses in COVID-19. Am J Resp Critical Care Med; 1 Mar 2023; DOI: 10.1164/rccm.202204-0751OC 

Individuals who are obese may be more susceptible to severe COVID-19 because of a poorer inflammatory immune response, say Cambridge scientists.

During the pandemic, the majority of younger patients I saw on the COVID wards were obese... I would have said that it was most likely due to excessive inflammation. What we found was the absolute oppositeMenna ClatworthyCambridge University Hospitals NHS Foundation TrustIntensive care unit at Addenbrooke's Hospital

The text in this work is licensed under a Creative Commons Attribution 4.0 International License. Images, including our videos, are Copyright ©University of Cambridge and licensors/contributors as identified.  All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

Yes

Scientists at the Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID) and Wellcome Sanger Institute showed that following SARS-CoV-2 infection, cells in the lining of the lungs, nasal cells, and immune cells in the blood show a blunted inflammatory response in obese patients, producing suboptimal levels of molecules needed to fight the infection.

Since the start of the pandemic, there have been almost 760 million confirmed cases of SARS-CoV-2 infection, with almost 6.9 million deaths. While some people have very mild – or even no – symptoms, others have much more severe symptoms, including acute respiratory distress syndrome requiring ventilator support.

One of the major risk factors for severe COVID-19 is obesity, which is defined as a body mass index (BMI) of over 30. More than 40% of US adults and 28% of adults in England are classed as obese.

While this link has been shown in numerous epidemiological studies, until now, it has not been clear why obesity should increase an individual’s risk of severe COVID-19. One possible explanation was thought to be that obesity is linked to inflammation: studies have shown that people who are obese already have higher levels of key molecules associated with inflammation in their blood. Could an overactive inflammatory response explain the connection?

Professor Menna Clatworthy is a clinician scientist at the University of Cambridge, studying tissue immune cells at CITIID alongside caring for patients at Addenbrooke’s Hospital, part of Cambridge University Hospitals NHS Foundation Trust. She said: “During the pandemic, the majority of younger patients I saw on the COVID wards were obese. Given what we know about obesity, if you’d asked me why this was the case, I would have said that it was most likely due to excessive inflammation. What we found was the absolute opposite.”

Clatworthy and her team analysed blood and lung samples taken from 13 obese patients with severe COVID-19 requiring mechanical ventilation and intensive care treatment, and 20 controls (non-obese COVID-19 patients and ventilated non-COVID-19 patients). These included patients admitted to the Intensive Care Unit at Addenbrooke’s Hospital.

Her team used a technique known as transcriptomics, which looks at RNA molecules produced by our DNA, to study activity of cells in these key tissues. Their results are published in the American Journal of Respiratory and Critical Care Medicine.

Contrary to expectations, the researchers found that the obese patients had underactive immune and inflammatory responses in their lungs.  In particular, when compared to non-obese patients, cells in the lining of their lungs and some of their immune cells had lower levels of activity among genes responsible for the production of two molecules known as interferons (INF) – interferon-alpha and interferon-gamma – which help control the response of the immune system, and of tumour necrosis factor (TNF), which causes inflammation.

When they looked at immune cells in the blood of 42 adults from an independent cohort, they found a similar, but less marked, reduction in the activity of interferon-producing genes as well as lower levels of IFN-alpha in the blood.

Professor Clatworthy said: “This was really surprising and unexpected. Across every cell type we looked at, we found that that the genes responsible for the classical antiviral response were less active. They were completely muted.”

The team was able to replicate its findings in nasal immune cells taken from obese children with COVID-19, where they again found lower levels of activity among the genes that produce IFN-alpha and IFN-gamma. This is important because the nose is one of the entry points for the virus – a robust immune response there could prevent the infection spreading further into the body, while a poorer response would be less effective.

One possible explanation for the finding involves leptin, a hormone produced in fat cells that controls appetite. Leptin also plays a role in the immune response: in individuals who are normal weight, levels of the hormone increase in response to infection and it directly stimulates immune cells. But obese people already have chronically higher levels of leptin, and Clatworthy says it is possible that they no longer produce sufficient additional leptin in response to infection, or are insensitive to it, leading to inadequate stimulation of their immune cells.

The findings could have important implications both for the treatment of COVID-19 and in the design of clinical trials to test new treatments.

Because an overactive immune and inflammatory response can be associated with severe COVID-19 in some patients, doctors have turned to anti-inflammatory drugs to dampen this response. But anti-inflammatory drugs may not be appropriate for obese patients.

Co-author Dr Andrew Conway Morris from the Department of Medicine at the University of Cambridge and Honorary Consultant on the intensive care unit at Addenbrooke’s Hospital said: “What we’ve shown is that not all patients are the same, so we might need to tailor treatments. Obese subjects might need less anti-inflammatory treatments and potentially more help for their immune system.”

Clinical trials for potential new treatments would need to involve stratifying patients rather than including both severe and normal weight patients, whose immune responses differ.

The research was largely supported by Wellcome, the Medical Research Council and the National Institute of Health and Care Research, including via the NIHR Cambridge Biomedical Research Centre.

Reference
Guo, SA, Bowyer, GS, Ferdinand, JR, Maes, M & Tuong, ZK et al. Obesity associated with attenuated tissue immune cell responses in COVID-19. Am J Resp Critical Care Med; 1 Mar 2023; DOI: 10.1164/rccm.202204-0751OC 

Individuals who are obese may be more susceptible to severe COVID-19 because of a poorer inflammatory immune response, say Cambridge scientists.

During the pandemic, the majority of younger patients I saw on the COVID wards were obese... I would have said that it was most likely due to excessive inflammation. What we found was the absolute oppositeMenna ClatworthyCambridge University Hospitals NHS Foundation TrustIntensive care unit at Addenbrooke's Hospital

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Yes

One Health In Action in the Caribbean

Chris will talk about the work he has been doing promoting the One Health approach across the Caribbean region. There has been a growing consensus that a One Health approach is necessary to address many of the health and development issues of today. His presentation will outline actions being taken to roll out the One Health approach to health challenges faced within the Caribbean, emphasizing the importance of collaboration and building partnerships. The presentation will describe two European Union funded projects that Chris has led. The “One Health One Caribbean One Love” and ‘Climate Change and One Health’ projects are example of ‘One Health in Action’. Both project are developing cohorts / networks of Caribbean professionals with the knowledge and skills to become change agents in their respective fields.

Chaired by Professor James Wood

• Speaker: Professor Chris Oura, School of Veterinary Medicine, University of the West Indies
• Thursday 11 May 2023, 16:00-17:00
• Venue: LT2.
• Series: Departmental Seminar Programme, Department of Veterinary Medicine; organiser: Fiona Roby.

Add to your calendar or Include in your list

One Health In Action in the Caribbean

Chris will talk about the work he has been doing promoting the One Health approach across the Caribbean region. There has been a growing consensus that a One Health approach is necessary to address many of the health and development issues of today. His presentation will outline actions being taken to roll out the One Health approach to health challenges faced within the Caribbean, emphasizing the importance of collaboration and building partnerships. The presentation will describe two European Union funded projects that Chris has led. The “One Health One Caribbean One Love” and ‘Climate Change and One Health’ projects are example of ‘One Health in Action’. Both project are developing cohorts / networks of Caribbean professionals with the knowledge and skills to become change agents in their respective fields.

Chaired by Professor James Wood

• Speaker: Professor Chris Oura, School of Veterinary Medicine, University of the West Indies
• Thursday 11 May 2023, 16:00-17:00
• Venue: LT2.
• Series: Departmental Seminar Programme, Department of Veterinary Medicine; organiser: Fiona Roby.

Add to your calendar or Include in your list

Heliyon. 2023 Mar;9(3):e14383. doi: 10.1016/j.heliyon.2023.e14383. Epub 2023 Mar 11.

ABSTRACT

Cigarette smoking has many serious negative health consequences. The relationship between smoking and SARS-CoV-2 infection is controversial, specifically whether smokers are at increased risk of infection. We investigated the impact of cigarette smoke on ACE2 isoform expression and SARS-CoV-2 infection in differentiated primary human bronchial epithelial cells at the air-liquid-interface (ALI). We assessed the expression of ACE2 in response to CSE and therapeutics reported to modulate ACE2. We exposed ALI cultures to cigarette smoke extract (CSE) and then infected them with SARS-CoV-2. We measured cellular infection using flow cytometry and whole-transwell immunofluorescence. We found that CSE increased expression of full-length ACE2 (flACE2) but did not alter the expression of a Type I-interferon sensitive truncated isoform (dACE2) that lacks the capacity to bind SARS-CoV-2. CSE did not have a significant impact on key mediators of the innate immune response. Importantly, we show that, despite the increase in flACE2, CSE did not alter airway cell infection after CSE exposure. We found that nicotine does not significantly alter flACE2 expression but that NRF2 agonists do lead to an increase in flACE2 expression. This increase was not associated with an increase in SARS-CoV-2 infection. Our results are consistent with the epidemiological data suggesting that current smokers do not have an excess of SARS-CoV-2 infection. but that those with chronic respiratory or cardiovascular disease are more vulnerable to severe COVID-19. They suggest that, in differentiated conducting airway cells, flACE2 expression levels may not limit airway SARS-CoV-2 infection.

PMID:36938474 | PMC:PMC10005841 | DOI:10.1016/j.heliyon.2023.e14383

Front Immunol. 2023 Mar 2;14:1028162. doi: 10.3389/fimmu.2023.1028162. eCollection 2023.

ABSTRACT

The biological processes underlying NK cell alloreactivity in haematopoietic stem cell transplantation (HSCT) remain unclear. Many different models to predict NK alloreactivity through KIR and MHC genotyping exist, raising ambiguities in its utility and application for clinicians. We assessed 27 predictive models, broadly divided into six categories of alloreactivity prediction: ligand-ligand, receptor-ligand, educational, KIR haplotype-based, KIR matching and KIR allelic polymorphism. The models were applied to 78 NGS-typed donor/recipient pairs undergoing allogeneic HSCT in genoidentical (n=43) or haploidentical (n=35) matchings. Correlations between different predictive models differed widely, suggesting that the choice of the model in predicting NK alloreactivity matters. For example, two broadly used models, educational and receptor-ligand, led to opposing predictions especially in the genoidentical cohort. Correlations also depended on the matching fashion, suggesting that this parameter should also be taken into account in the choice of the scoring strategy. The number of centromeric B-motifs was the only model strongly correlated with the incidence of acute graft-versus-host disease in our set of patients in both the genoidentical and the haploidentical cohorts, suggesting that KIR-based alloreactivity, not MHC mismatches, are responsible for it. To our best knowledge, this paper is the first to experimentally compare NK alloreactivity prediction models within a cohort of genoidentical and haploidentical donor-recipient pairs. This study helps to resolve current discrepancies in KIR-based alloreactivity predictions and highlights the need for deeper consideration of the models used in clinical studies as well as in medical practice.

PMID:36936953 | PMC:PMC10017772 | DOI:10.3389/fimmu.2023.1028162

Phytopathology. 2023 Mar 19. doi: 10.1094/PHYTO-02-23-0069-IA. Online ahead of print.

ABSTRACT

A synoptic review of plant disease epidemics and outbreaks was made using two complementary approaches. The first approach involved reviewing scientific literature published in 2021; the second approach involved retrieving new records added in 2021 to the CABI Distribution Database. The literature review retrieved 186 articles, describing studies in 62 categories (pathogen species/species complexes) across >40 host species on 6 continents. Pathogen species with >5 articles were: Bursaphelenchus xylophilus, Candidatus Liberibacter asiaticus, cassava mosaic viruses, citrus tristeza virus, Erwinia amylovora, Fusarium spp. complexes, Fusarium oxysporum f. sp. cubense, Magnaporthe oryzae, maize lethal necrosis co-infecting viruses, Meloidogyne spp. complexes, Pseudomonas syringae pvs, Puccinia striiformis f. sp. tritici, Xylella fastidiosa, and Zymoseptoria tritici. Automated searches of the CABI Distribution Database identified 617 distribution records new in 2021 of 283 plant pathogens. A further manual review of these records confirmed 15 pathogens reported in new locations: apple hammerhead viroid, apple rubbery wood viruses, Aphelenchoides besseyi, Biscogniauxia mediterranea, Ca. Liberibacter asiaticus, citrus tristeza virus, Colletotrichum siamense, cucurbit chlorotic yellows virus, Erwinia rhapontici, Erysiphe corylacearum, Fusarium oxysporum f. sp. cubense Tropical Race 4, Globodera rostochiensis, Nothophoma quercina, potato spindle tuber viroid, and tomato brown rugose fruit virus. Of these, 4 pathogens had at least 25% of all records reported in 2021. We assessed two of these pathogens - tomato brown rugose fruit virus and cucurbit chlorotic yellows virus - to be actively emerging in/spreading to new locations. In general our dual approaches revealed distinct sets of plant disease outbreaks and new records, with little overlap.

PMID:36935375 | DOI:10.1094/PHYTO-02-23-0069-IA

Protist. 2023 Feb 28:125947. doi: 10.1016/j.protis.2023.125947. Online ahead of print.

NO ABSTRACT

PMID:36935326 | DOI:10.1016/j.protis.2023.125947

Commun Biol. 2023 Mar 16;6(1):277. doi: 10.1038/s42003-023-04589-5.

ABSTRACT

Expanding the arsenal of prophylactic approaches against SARS-CoV-2 is of utmost importance, specifically those strategies that are resistant to antigenic drift in Spike. Here, we conducted a screen of over 16,000 RNAi triggers against the SARS-CoV-2 genome, using a massively parallel assay to identify hyper-potent siRNAs. We selected Ten candidates for in vitro validation and found five siRNAs that exhibited hyper-potent activity (IC50 < 20 pM) and strong blockade of infectivity in live-virus experiments. We further enhanced this activity by combinatorial pairing of the siRNA candidates and identified cocktails that were active against multiple types of variants of concern (VOC). We then examined over 2,000 possible mutations in the siRNA target sites by using saturation mutagenesis and confirmed broad protection of the leading cocktail against future variants. Finally, we demonstrated that intranasal administration of this siRNA cocktail effectively attenuates clinical signs and viral measures of disease in the gold-standard Syrian hamster model. Our results pave the way for the development of an additional layer of antiviral prophylaxis that is orthogonal to vaccines and monoclonal antibodies.

PMID:36928598 | DOI:10.1038/s42003-023-04589-5

Microbiol Mol Biol Rev. 2023 Mar 16:e0008022. doi: 10.1128/mmbr.00080-22. Online ahead of print.

ABSTRACT

The quest for bacterial survival is exemplified by spores formed by some Firmicutes members. They turn up everywhere one looks, and their ubiquity reflects adaptations to the stresses bacteria face. Spores are impactful in public health, food safety, and biowarfare. Heat resistance is the hallmark of spores and is countered principally by a mineralized gel-like protoplast, termed the spore core, with reduced water which minimizes macromolecular movement/denaturation/aggregation. Dry heat, however, introduces mutations into spore DNA. Spores have countermeasures to extreme conditions that are multifactorial, but the fact that spore DNA is in a crystalline-like nucleoid in the spore core, likely due to DNA saturation with small acid-soluble spore proteins (SASPs), suggests that reduced macromolecular motion is also critical in spore dry heat resistance. SASPs are also central in the radiation resistance characteristic of spores, where the contributions of four spore features-SASP; Ca2+, with pyridine-2,6-dicarboxylic acid (CaDPA); photoproduct lyase; and low water content-minimize DNA damage. Notably, the spore environment steers UV photochemistry toward a product that germinated spores can repair without significant mutagenesis. This resistance extends to chemicals and macromolecules that could damage spores. Macromolecules are excluded by the spore coat which impedes the passage of moieties of ≥10 kDa. Additionally, damaging chemicals may be degraded or neutralized by coat enzymes/proteins. However, the principal protective mechanism here is the inner membrane, a compressed structure lacking lipid fluidity and presenting a barrier to the diffusion of chemicals into the spore core; SASP saturation of DNA also protects against genotoxic chemicals. Spores are also resistant to other stresses, including high pressure and abrasion. Regardless, overarching mechanisms associated with resistance seem to revolve around reduced molecular motion, a fine balance between rigidity and flexibility, and perhaps efficient repair.

PMID:36927044 | DOI:10.1128/mmbr.00080-22

Gene-based vaccines to combat bacterial diseases, hurdles and opportunities’

With the recent success of adenoviral vaccines against Ebola and SARS -CoV-2, the potential of this platform in the fight against outbreak pathogens is being realised. This technology has proven impact in high income countries and is also suitable for large scale manufacture and use in low-and-middle income countries, as demonstrated by the Oxford/AstraZeneca vaccine against SARS -CoV-2. The potential of viral-vectors to induce T Helper type 1 and high antibody responses in humans makes the use of this approach attractive in efforts to combat the disease and disability caused by bacterial pathogens. However, the case for their use in bacterial vaccines is less clear: the expression of a bacterial protein in a eukaryotic cell may impact on the antigen localization, induce unwanted glycosylation or affect protein conformation, and this is also true if using the mRNA vaccine platform. The potential and challenges of adenoviral vectors was explored against two bacterial diseases, capsular group B meningococcus and the plague. While all antigens and combinations were able to induce high antibody responses after a single dose immunisation in mice, not all were able to induce functional antibodies. We show that a subset of outer membrane proteins from Gram-negative bacteria can be incorporated into gene-based vectors for novel vaccine development. While our work highlights the challenges inherent in developing novel vaccines using this technology and can be applied to mRNA, the successful progression of two novel bacterial vaccines to clinical development underlines the potential of these platforms for vaccine development against bacterial diseases.

Canceled - to be re-scheduled

• Speaker: Professor Christine Rollier, Professor of Vaccinology, University of Surrey
• Wednesday 24 May 2023, 13:00-14:00
• Venue: LT2.
• Series: Departmental Seminar Programme, Department of Veterinary Medicine; organiser: Fiona Roby.

Add to your calendar or Include in your list

Gene-based vaccines to combat bacterial diseases, hurdles and opportunities’

With the recent success of adenoviral vaccines against Ebola and SARS -CoV-2, the potential of this platform in the fight against outbreak pathogens is being realised. This technology has proven impact in high income countries and is also suitable for large scale manufacture and use in low-and-middle income countries, as demonstrated by the Oxford/AstraZeneca vaccine against SARS -CoV-2. The potential of viral-vectors to induce T Helper type 1 and high antibody responses in humans makes the use of this approach attractive in efforts to combat the disease and disability caused by bacterial pathogens. However, the case for their use in bacterial vaccines is less clear: the expression of a bacterial protein in a eukaryotic cell may impact on the antigen localization, induce unwanted glycosylation or affect protein conformation, and this is also true if using the mRNA vaccine platform. The potential and challenges of adenoviral vectors was explored against two bacterial diseases, capsular group B meningococcus and the plague. While all antigens and combinations were able to induce high antibody responses after a single dose immunisation in mice, not all were able to induce functional antibodies. We show that a subset of outer membrane proteins from Gram-negative bacteria can be incorporated into gene-based vectors for novel vaccine development. While our work highlights the challenges inherent in developing novel vaccines using this technology and can be applied to mRNA, the successful progression of two novel bacterial vaccines to clinical development underlines the potential of these platforms for vaccine development against bacterial diseases.

Canceled - to be re-scheduled

• Speaker: Professor Christine Rollier, Professor of Vaccinology, University of Surrey
• Wednesday 24 May 2023, 13:00-14:00
• Venue: LT2.
• Series: Departmental Seminar Programme, Department of Veterinary Medicine; organiser: Fiona Roby.

Add to your calendar or Include in your list

Gene-based vaccines to combat bacterial diseases, hurdles and opportunities’

With the recent success of adenoviral vaccines against Ebola and SARS -CoV-2, the potential of this platform in the fight against outbreak pathogens is being realised. This technology has proven impact in high income countries and is also suitable for large scale manufacture and use in low-and-middle income countries, as demonstrated by the Oxford/AstraZeneca vaccine against SARS -CoV-2. The potential of viral-vectors to induce T Helper type 1 and high antibody responses in humans makes the use of this approach attractive in efforts to combat the disease and disability caused by bacterial pathogens. However, the case for their use in bacterial vaccines is less clear: the expression of a bacterial protein in a eukaryotic cell may impact on the antigen localization, induce unwanted glycosylation or affect protein conformation, and this is also true if using the mRNA vaccine platform. The potential and challenges of adenoviral vectors was explored against two bacterial diseases, capsular group B meningococcus and the plague. While all antigens and combinations were able to induce high antibody responses after a single dose immunisation in mice, not all were able to induce functional antibodies. We show that a subset of outer membrane proteins from Gram-negative bacteria can be incorporated into gene-based vectors for novel vaccine development. While our work highlights the challenges inherent in developing novel vaccines using this technology and can be applied to mRNA, the successful progression of two novel bacterial vaccines to clinical development underlines the potential of these platforms for vaccine development against bacterial diseases.

Canceled - to be re-scheduled

• Speaker: Professor Christine Rollier, Professor of Vaccinology, University of Surrey
• Wednesday 24 May 2023, 13:00-14:00
• Venue: LT2.
• Series: Departmental Seminar Programme, Department of Veterinary Medicine; organiser: Fiona Roby.

Add to your calendar or Include in your list