Bristol BioDesign Institute blog
BioDesign: biomolecules to biosystems, from understanding to design
Congratulations to the team at Halo Therapeutics, who have won the ‘BioSeed ‘One to Watch’ Award for Therapeutics’ at the OBN Awards. Halo is developing pan coronavirus antivirals for home use by COVID-19 patients, based on groundbreaking discoveries made during the lockdowns. The award was collected by Prof Imre Berger, who is co-founder and CSO of Halo, and a Co-Director of the Bristol BioDesign Institute. Halo was founded on IP generated through BrisSynBio.
In a recent policy paper, the UK Government have outlined an Innovation Strategy, which sets out their ambitions for an innovation-led economy. Zentraxa, an exciting spin-out of bioengineering researchers from the Bristol BioDesign Institute and the University of Bristol, have been featured in the document ‘UK Innovation Strategy: Leading the future by creating it’. This strategy focuses on how the government can support businesses innovate by making the most of the UK’s research, development and innovation system, to make the UK a global hub for innovation.
Zentraxa is manufacturing biopolymers for use in highly functional adhesives in medical and industrial settings and are establishing a new niche in the synthetic peptides market. They have been highlighted in the UK Innovation Strategy as an example of a highly-successful pioneer in this type of research. Co-founder and Director of Zentraxa, Paul Race, is a University of Bristol Professor of Biological Chemistry who set up the spin-out in 2017. From 2014-17 he served as Co-Director of the >£14M Bristol Centre for Synthetic Biology Research (BrisSynBio) and was a founding Director of the Bristol BioDesign Institute.
See the Zentraxa case-study on page 30 of the UK Innovation Strategy. Congratulations to the Zentraxa team for this recognition!
Over the past year the BBI have contributed expertise, equipment and resources to support UNCOVER, Bristol University COVID-19 Emergency Research Response Group.
Bristol based photographer Tom Skipp has captured portraits of some of the people involved, including BBI Director Dek Woolfson. Tom was motivated to tell the human stories behind the people at Bristol who are playing an important role in global efforts to overcome COVID-19.
A series of these portraits are part of a billboard campaign on show at various locations across Bristol until the 9th May.
Image credit: Tom Skipp
A team of scientists from the University of Bristol, including BBI Director Professor Imre Berger, have formed a new biotech spin-out company ‘Halo Therapeutics Ltd’ that is developing potential treatments for coronavirus.
The scientists behind Halo Therapeutics were responsible for the breakthrough discovery of a molecule that changes the shape of the SARS-CoV-2 virus spike protein, which was published in Science. Professor Imre Berger, one of the team leading the drug’s development, explained: “The aim of our treatment is to significantly reduce the amount of virus that enters the body and to stop it from multiplying. Then, even if people are infected with the virus or exposed to it, they will not become ill because the antiviral prevents the virus from spreading to the lungs and beyond. Importantly, because the viral load will be so low it will likely also stop transmission.”
Halo Therapeutics Ltd is preparing for clinical trials. If proven to be effective, the antivirals could be used by people of all ages worldwide at the first sign of COVID-19 symptoms, or if they have been in contact with someone with the virus, preventing the virus from taking hold and stopping further transmission.
Studies show the treatments are potentially ‘pan-corona antivirals’ in that they will work against all coronavirus strains – including the highly contagious ‘UK (Kent)’, ‘South African’ and ‘Brazilian’ variants. Some examples of treatments that Halo are currently developing include a nasal spray and inhaler. The antiviral also has the potential to treat patients at all stages of covid-19 and to reduce transmissibility.
Coordinated by the University of Bristol, the ADDovenom Project engages in research on snakebite venom, from which thousands of people die each year. The University of Bristol, alongside the University of Liège, Aix-Marseille University, Liverpool School of Tropical Medicine and iBET, will use novel snakebite therapy to research antivenoms. Project Coordinator, Professor Christiane Berger-Schaffitzel, says –
“Our ultimate goal is to provide a low-cost, easy-to-produce, safe to administer, clinically effective and low dose type of antivenom that can be stored and used for community treatment ideally at the point-of-care – a substantial therapeutic advance to reduce the global mortality of venomous snake-bites.”
For updates on this interdisciplinary research venture take a look at the ADDovenom website, where you can find latest news items, research information, details on partners, and the experts behind the project.
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.
In a tribute to University of Bristol Professors Christiane Berger-Schaffitzel and Imre Berger‘s research, scientists use virtual reality to depict the novel pocket in the SARS-CoV-2 spike protein.
The discovery, in a group research paper led by Berger-Schaffitzel, finds that linoleic acid binds to a ‘druggable’ pocket in the spike protein’s protomers, which prevents the virus from attaching to human ACE2 receptors. The video visualises how a gating helix within one of the protomers opens to accommodate the linoleic acid in the pocket, as well as how Arginine 408 and Glutamine 409 interact with the linoleic acid, which acts like a ‘lid’ over the pocket to keep the molecule tightly bound.
Research study discussed: Toelzer et al. (2020). ‘Free fatty acid binding pocket in the locked structure of SARS-CoV-2 spike protein‘. Science. eabd3255. doi:10.1126/science.abd3255s.
Since the start of lockdown 1.0 in March 2020, the BBI has been hosting a series of virtual seminars. Speakers have included Professors Anne Osbourn, Christine Orengo, Andreas Plueckthun, and many others. Lockdown has allowed us to broaden our speaker base on an international level, with academics from the US, Israel and Switzerland.
On 11 November, we had Professor Domitilla Del Vecchio from the Massachusetts Institute of Technology (MIT) give a webinar on ‘Context dependence of biological circuits: Predictive models and engineering solutions’. Panellists for the event were some of our own University of Bristol academics Dr. Thomas Gorochowski and Prof. Claire Grierson.
You can watch the full recording of the webinar here:
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.
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.”