Photographer captures the human stories behind UNCOVER research

Bristol photographer Tom Skipp has been working with the UNCOVER Group to understand the human stories and motivations behind the people who are playing a role in global efforts to overcome COVID-19.

Tom was concerned by what he felt was a public distrust of science and an anecdotal feeling that minority populations might be dissuaded to take a vaccine given a historic prejudice by institutions. He felt that scientists are perceived as inaccessible, usually only seen on pedestals or next to government officials disseminating statistics, and limiting civil liberties.

Dr Rajeka LazarusBy meeting some of the people involved in the UNCOVER group, Tom hoped to understand their stories and motivations and relate those to the people of Bristol on a street level. Tom has captured a series of portraits some of which are part of a billboard campaign on show at various locations across Bristol until the 9th May.

Dr Rajeka Lazarus, consultant in infectious diseases and microbiology at University Hospitals Bristol and Weston, runs COVID vaccine trials and has been motivated by the impact of COVID on minoritized populations.

Dr Ore Francis, a post-doctoral research assistant developing a SARS-CoV-2 pseudovirus to make COVID research faster and safer.  He has been motivated by the generosity of people donating samples and resourced to the global COVID research efforts.

Talking about his project, Tom said: “These photographs are all taken where the people have been carrying out their work over the last year, in university labs, hospitals and at home. They’ve all been experiencing the daily struggles and burdens put upon all of us by the pandemic with the added pressure of having the capabilities to do something about it.”

Dr Ore Francis

  • 92-98 Kingsland Road, BS2 0QZ – Drs Ore Francis, Research Associate, and Rajeka Lazarus, a consultant in infectious diseases and microbiology at UHBW
  • 28 Stapleton Road, BS5 0QX – Dek Woolfson, Professor of Chemistry and Biochemistry and Director of the Bristol BioDesign Institute
  • 34 Ashley Road, BS6 5NS – Adam Finn, Professor of Paediatrics at Bristol, Director of the Bristol Vaccine Centre at Bristol Medical School and lead of Bristol UNCOVER Group
  • 265 Church Road, BS5 9HU – Dr David Mathews, Reader in Virology
  • Electric Ladyland, Trinity Road, BS2 0FJ – Dr Christy Waterfall, Senior Research Associate

Image credit: Tom Skipp 

Genotype to Phenotype National Virology Consortium Launched

A national research project to study the effects of emerging mutations in SARS-CoV-2 has been launched. The £2.5 million UK Research and Innovation (UKRI)-funded ‘G2P-UK’ National Virology Consortium will study how mutations in the virus affect key outcomes such as how transmissible it is, the severity of COVID-19 it causes, and the effectiveness of vaccines and treatments.

The Consortium will bring together leading virologists from ten research institutions including Drs Andrew Davidson and David Matthews from the University of Bristol. They will work alongside the COVID-19 Genomics UK (COG-UK) consortium, which plays a world-leading role in virus genome sequencing, and Public Health England to boost the UK’s capacity to study newly identified virus variants and rapidly inform government policy.

The consortium is led by Professor Wendy Barclay, from Imperial College London, who said: “The UK has been fantastic in sequencing viral genomes and identifying new variants – now we have to better understand which mutations affect the virus in a way that might affect our control strategies. We are already working to determine the effects of the recent virus variants identified in the UK and South Africa and what that means for the transmission of SARS-CoV-2 and vaccine effectiveness.”

Bristol will be leading on the application of synthetic biology approaches to engineer synthetic pesudovirus platform technologies to probe virus infectivity.

Interactive virtual reality emerges as a new tool for drug design against COVID-19

Bristol scientists have demonstrated a new virtual reality [VR] technique which should help in developing drugs against the SARS-CoV-2 virus – and enable researchers to share models and collaborate in new ways. The innovative tool, created by University of Bristol researchers, and published in the Journal of Chemical Information and Modeling, will help scientists around the world identify anti-viral drug leads more rapidly.

A cartoon showing iMD-VR being used to model how a viral protein binds to the SARS-CoV-2 main protease
A cartoon showing iMD-VR being used to model how a viral protein binds to the SARS-CoV-2 main protease

Interactive molecular dynamics in virtual reality (iMD-VR) is an effective tool for flexible substrate and inhibitor docking to the SARS-CoV-2 main protease’ by A Mulholland et al in the Journal of Chemical Information and Modeling

Neuropilin-1 drives SARS-CoV-2 infectivity, finds breakthrough study

In this breakthrough study, the research groups in Bristol’s Faculty of Life Sciences, Professor Peter Cullen from the School of Biochemistry; Dr Yohei Yamauchi, Associate Professor and virologist from the School of Cellular and Molecular Medicine, and Dr Boris Simonetti, a senior researcher in the Cullen lab, used multiple approaches to discover that SARS-CoV-2 recognises a protein called neuropilin-1 on the surface of human cells to facilitate viral infection.

Neuropilin-1 is a host factor for SARS-CoV-2 infection

James L. Daly, Boris Simonetti, Katja Klein, Kai-En Chen, Maia Kavanagh Williamson, Carlos Antón-Plágaro, Deborah K. Shoemark, Lorena Simón-Gracia, Michael Bauer, Reka Hollandi, Urs F. Greber, Peter Horvath, Richard B. Sessions, Ari Helenius, Julian A. Hiscox, Tambet Teesalu, David A. Matthews, Andrew D. Davidson, Brett M. Collins, Peter J. Cullen1, Yohei Yamauchi

Science  20 Oct 2020: DOI: 10.1126/science.abd3072

https://science.sciencemag.org/content/early/2020/10/19/science.abd3072

Druggable pocket discovered in SARS-CoV-2 Spike protein could stop virus spread

An international team of scientists, led by University of Bristol Professors Christiane Schaffitzel and Imre Berger, have unearthed a druggable pocket in the SARS-CoV-2 Spike protein that could be used to stop the virus in its tracks. ‘Spike protein’ refers to the multiple copies of glycoprotein that surround SARS-CoV-2. These ‘spikes’ bind to human cells, allowing the virus to penetrate the cells and replicate, damaging as they go. The collaborative study of SARS-CoV-2 is comprised of experts from Bristol UNCOVER Group, Bristol biotech Imophoron Ltd, the Max Planck Institute in Heidelberg and Geneva Biotech Sàrl.

Professor Christiane Schaffitzel from the School of Biochemistry
Professor Christiane Schaffitzel from the School of Biochemistry

The team analysed the SARS-CoV-2 Spike protein at near atomic resolution by applying electron cryo-microscopy (Cryo-EM) and Oracle’s high-performance cloud computing to produce a 3D image of the virus’s molecular composition. After getting a look at the virus up-close, the scientists spotted a potential ‘game changer’ in defeating the current pandemic.

The researchers spotted the presence of a free fatty acid; linoleic acid (LA), hidden away in a pocket within the Spike protein. LA is vital to most cellular functions in humans. It is not naturally produced by the body, so humans must intake LA through diet. The acid helps to maintain cell membranes in the lungs, and regulates inflammation and immune modulation, which are all the functions that are implicated in Covid-infected patients. Professor Berger, Director of the Max Planck Bristol Centre for Minimal Biology, confirms that “the virus that is causing all this chaos, according to our data, grabs and holds on to exactly this molecule – basically disarming much of the body’s defences.”

Professor Schaffitzel, from the University of Bristol’s School of Biochemistry, explained: “From other diseases we know that tinkering with LA metabolic pathways can trigger systemic inflammation, acute respiratory distress syndrome and pneumonia. These pathologies are all observed in patients suffering from severe COVID-19. A recent study of COVID-19 patients showed markedly reduced LA levels in their sera.”

The exploitation of the druggable pocket containing LA in SARS-CoV-2 could be the key to manipulating the virus. The discovery of a druggable pocket has previously been successfully exploited in rhinovirus, which causes the common cold. In rhinovirus, small molecules were tightly bound to the pocket to distort its molecular structure, and prevent its infectivity in human cells. The team are optimistic that their discovery of a similar pocket in SARS-CoV-2 can be used to develop small molecule anti-viral drugs against it.

Professor Berger adds: “Our discovery provides the first direct link between LA, COVID-19 pathological manifestations and the virus itself. The question now is how to turn this new knowledge against the virus itself and defeat the pandemic.”

Stopping the spread of coronavirus in universities

Infectious disease modelling experts at the University of Bristol have conducted a rapid review and developed a new epidemic model which contributed to evidence considered by SAGE to assess the effectiveness of different interventions that could stop the spread of SARS-CoV-2 in a university setting. The findings have provided the sector with recommendations to help reduce the risk for students, staff and the wider community.

COVID-19 transmission in a university setting: a rapid review of modelling studies

Hannah Christensen, Katy Turner, Adam Trickey, Ross D Booton, Gibran Hemani, Emily Nixon, Caroline Relton, Leon Danon, Matthew Hickman, Ellen Brooks Pollock

doi: https://doi.org/10.1101/2020.09.07.20189688

High COVID-19 transmission potential associated with re-opening universities can be mitigated with layered interventions

Ellen Brooks-Pollock, Hannah Christensen, Adam Trickey, Gibran Hemani, Emily Nixon, Amy Thomas, Katy Turner, Adam Finn, Matt Hickman, Caroline Relton, Leon Danon

doi: https://doi.org/10.1101/2020.09.10.20189696

Analysis of seven trials finds that corticosteroids reduce risk of death by 20 per cent in critically ill COVID-19 patients

A team led by Jonathan Sterne, Professor of Medical Statistics and Epidemiology, and Deputy Director of the NIHR Bristol Biomedical Research Centre (NIHR Bristol BRC) has conducted a meta-analysis of seven trials and found that corticosteroids reduce the risk of death among critically ill COVID-19 patients by 20 per cent. The team included international collaborators and was co-ordinated by the World Health Organisation (WHO). The study looked at mortality over a 28-day period after the start of treatment. They found that treatment with one of the three corticosteroids dexamethasone, hydrocortisone or methylprednisolone led to an estimated 20 per cent reduction in the risk of death. The dexamethasone finding is mainly based on results from the RECOVERY trial, which were included in the analysis.

Association Between Administration of Systemic Corticosteroids and Mortality Among Critically Ill Patients With COVID-19

A Meta-analysis

The WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group

Article Information

JAMA. 2020;324(13):1330-1341. doi:10.1001/jama.2020.17023

https://jamanetwork.com/journals/jama/fullarticle/2770279

New Covid-19 Study could Restart the Arts

A science experiment or a film set?

During the coronavirus pandemic, many countries have effectively banned group singing and playing of woodwind and brass instruments. Although there have been several clusters of Covid-19 noted in choirs around the world, there is no concrete evidence to link these cases to the acts of playing and singing. The University of Bristol, Imperial College London, Wexham Park Hospital, Lewisham and Greenwich NHS Trust, Royal Brompton Hospital and ARUP have all banded under the name PERFORM for a Covid-19 research project to tackle this problem.

PERFORM (ParticulatE Respiratory Matter to InForm Guidance for the Safe Distancing of PerfOrmeRs in a COVID-19 PandeMic), supported by Public Health England, will explore whether singing and playing brass and woodwind instruments produces more respiratory particles than when speaking. These aerosol experts will also be investigating whether venue temperature and size affects the amount of aerosol droplets produced.

The CELEBS instrument at Bristol for studying the airborne transmission of SARS-CoV-2 in a high containment lab.

Airborne droplets of a similar diameter to a human hair enable the transmission of the Covid-19 virus through sneezing, coughing, speaking, and even breathing. These droplets can contaminate surfaces up to two metres away that unsuspecting individuals may later touch. And equally troubling are smaller (10 micrometres!), respirable particles that can remain airborne hours after a sneeze, or singing.

Prof. Jonathan Reid from the University of Bristol has been determining whether aerosol droplets could be a culprit in the transmission of the virus. A PERFORM experiment at the University of Bristol includes individuals singing and speaking between the decibel (dB) ranges of 50–60, 70-80 and 90-100 dB. The Langford Vet School and the School of Cellular and Molecular Medicine at Bristol are also exploring how long the virus survives at certain temperatures and relative levels of humidity. They have been in operating theatres working with clinicians to quantify aerosols produced from aerosol generating procedures, such as extubation and intubation.

Measuring the aerosol generated from a cough in an operating theatre, to better understand the risks of aerosol generating
procedures such as extubations.

The results from the Bristol study in conjunction with other outcomes in the PERFORM collaboration efforts against Covid-19 will help to provide more robust evidence for guidance on social distancing, and may provide an answer to the currently uncertain future of choirs and orchestras around the world.

Charities join forces to understand how COVID-19 affects people with type 1 diabetes

JDRF and Diabetes UK will co-fund Professor Kathleen Gillespie, at the University of Bristol, to find out why the risk of death from Covid-19 is higher in those who are type 1 diabetic. Scientists don’t know how many people with type 1 have had coronavirus and recovered, obscuring the full impact that the virus is having on the UK’s 400,000 people with type 1.

Professor Gillespie’s team will work with a research group in Milan that has developed a test that can detect coronavirus antibodies in a small sample of blood – small enough to be collected via post. By offering this test to around 5,000 people participating in ongoing studies of type 1 diabetes (the Bart’s Oxford study and UK TrialNet), Professor Gillespie will be able to estimate how many people contracted coronavirus. She will also ask participants to share their experiences of COVID-19 and lockdown – including whether they have been shielding, if they have had any COVID-19 symptoms, and how their blood glucose levels have reacted. With this information, Professor Gillespie will be able to see how the type 1 diabetes community has been hit by COVID-19. This will give scientists and clinicians a clearer idea of the risk that coronavirus poses to people with type 1, enabling healthcare teams to better support and protect people with the condition.

Early COVID-19 research – the bedrock for scientific next steps

Guest Blog: Elizabeth Blackwell Institute Director Professor Rachael Gooberman-Hill

Blog 6 July 2020

EBI Director

Early COVID-19 research – the bedrock for scientific next steps

Research at Bristol has risen to the challenge of SARS-CoV-2 and the disease it causes, COVID-19. Since the start of the pandemic, colleagues across the University have taken huge strides to use their expertise to move quickly on work that addresses the immediate and longer-term questions around the virus.

Here at the Elizabeth Blackwell Institute we’ve run a funding call to support research across all faculties and disciplines; designed to support research with as little bureaucracy as possible and maximum impact. We’ve supported over 60 projects in total in the space of three months, with around half of them in the UNCOVER group – an emergency research group at the University of Bristol set up specifically to tackle COVID-19.

Elizabeth Blackwell Institute funded COVID-19 research

The Elizabeth Blackwell Institute has been helping scientists to plant their seeds and it’s satisfying to watch them grow. The UNCOVER group’s work is high quality, and its success is down to the hard work of everyone involved, who have all worked fast and with massive efficiency. At the Elizabeth Blackwell Institute we’re going to learn from the streamlined research funding processes that we’ve been able to use over recent months.

Discoveries from UNCOVER are already being published so that the international research community can use it straight away. It’s making steps in important directions, particularly in our understanding of transmission, treatment and prevention of COVID-19. UNCOVER includes work here at Bristol and in partnership with others, and is underpinning proposals to major research funders. Some of the research completed already, just within a few months, is providing the bedrock for the next steps in the science.

I’ve been overawed from the start by the energy and commitment of Bristol’s staff in the research response to the pandemic, our thanks from all at the Elizabeth Blackwell Institute for your hard work.