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.
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
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.
This webinar is a spotlight on plant synthetic biology, featuring three rising stars in one dynamic interactive session. Three early career researchers, hosted by Dr. Thomas Gorochowski and Dr. Emily Larson, discuss plant biology topics including reprogramming plant root growth, genome engineering, and the biodesign potential of marchantia polymorpha. The speakers include:
Dr. Jennifer Brophy (keynote) – ‘Reprogramming plant root growth using synthetic developmental regulation.’
Dr Quentin Dudley – ‘Genome engineering of Nicotiana benthamiana as an improved plant-based bioproduction system for medicinal alkaloids.’
Dr Eftychis Frangedakis – ‘Marchantia polymorpha: an emerging system for plant synthetic biology.’
You can watch the full recording, including Q&A here:
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 ADDovenom team at the October 2020 kick-off meeting~
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.
The Bristol BioDesign Institute‘s newly imagined webinar series for 2021 has been designed as a platform to invite the best international speakers that are aligned to our core areas of interest. These include; biomolecular design and assembly in the cell, development and delivery of bioactive molecules, minimal biology towards cell-like systems, advanced computing and digital biology. You can find our upcoming speakers for the year on the International Webinar Series section of our website.
The first speaker of 2021 is Professor Elisa Franco from UCLA, with BBI Directors, Thomas Gorochowski and Dek Woolfson, panelling. The seminar is followed by an audience Q&A session, and then a one-to-one interview where Dr. Gorochowski asks Professor Franco questions about how she got into synthetic biology and her predictions for its future.
You can watch Professor Franco’s seminar, on ‘Programming dynamic behaviors in molecular systems and materials‘ below, or on the BBI YouTube Channel.
Abstract – Biological cells adapt, replicate, and self-repair in ways that are unmatched by man-made devices. These processes are enabled by the interplay of receptors, gene networks, and self-assembling cytoskeletal scaffolds. Taking inspiration from this architecture, we follow a reductionist approach to build synthetic materials by interconnecting nucleic acid components with the capacity to sense, compute, and self-assemble. Nucleic acids are versatile molecules whose interactions and kinetic behaviors can be rationally designed from their sequence content; further, they are relevant in a number of native and engineered cellular pathways, as well as in biomedical and nanotechnology applications. I will illustrate our approach with two examples. The first is the construction of self-assembling DNA scaffolds that can be programmed to respond to environmental inputs and to canonical molecular signal generators such as pulse generators and oscillators. The second is the encapsulation of these dynamic scaffolds in droplets serving as a mimic of cellular compartments. I will stress how mathematical modeling and quantitative characterization can help identify design principles, guide experiments, and explain observed phenomena.
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.
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.
Professor Imre Berger, Max Planck Bristol Director and Bristol BioDesign Institute Director
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 Christiane Schaffitzel from the School of Biochemistry
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.”
On the 31st October 2019, the Transforming UK Translation conference was held, bringing together Universities and Research Institutes to exchange ideas on bridging industry with academia. Hosted by the Royal Society, the Academy of Medical Sciences, the Royal Academy of Engineering and the Wellcome Trust, this one-off event was designed to address eight commitments in the Transforming UK Translation 10-year plan. Commitments from the hosts include opening training and development opportunities, fostering a system that rewards translation as part of research excellence, and that all work produced will have wider societal benefits.
Dek Woolfson
There were over 200 people in attendance, including our Royal Society Entrepreneur in Residence, David Tew, and BBI Director Prof Dek Woolfson. Meetings throughout the day consisted of talks, workshops and round table discussions with key stakeholders to address industry-academia engagements, their mutually beneficial partnerships and how to attract and train the right talent to drive these engagements.
A well-oiled machine: Lessons from Cambridge
An instance of successful translation is The Cambridge Department of Computer Science and Technology. In 20 years, they have founded over 270 companies. More than half of these are still active in 2020 with combined revenues of $1 billion and upwards. Their translational strategy is successful for several reasons:
Staff are encouraged by the department to be both entrepreneurs and academics simultaneously, which creates spin-outs and attracts business-minded researchers to the University in a continuous loop.
All negotiations regarding Intellectual Property are dealt with outside of the University to maintain positive relationships between entrepreneurs and businesses.
Entrepreneurial staff are encouraged and willing to mentor other industry hopefuls to create a supportive working environment. Friendly competition is welcomed with annual prizes given out.
Academics have space to develop companies more and publish a little less.
The department launches as many prospective businesses as possible rather than being selective. They aim to reduce negotiation time between all parties to help drive the quantity of start-ups.
The ‘golden share’ method is utilised when negotiating start-up contracts, where the University owns 2-3% of a company, but has control of at least 51% of the voting rights. This model is far easy to negotiate, is quicker to sort contracts and doesn’t dilute the University’s stake in the business.
For companies relatively new to the start-up businesses, like Bristol, there are a lot of lessons we can learn from this model. Having only started our first BrisSynBio spin-out in 2017, Bristol University is in its early stages of transforming translation.
BrisSynBio: The new kids on the block
At the conference, BrisSynBio at the University of Bristol was used as a successful example of thriving industry-academia collaboration. BrisSynBio is one of only six Synthetic Biology Research Centres in the UK, funded by BBSRC and EPSRC. BrisSynBio’s research focuses on aspects of biomolecular design and engineering and applying these in the field of synthetic biology. An Innovation Manager post was created to translate novel areas of synthetic biology research into real-life application. There are four UoB spin-out companies; Cytoseek, Imophoron Ltd, Rosa biotech and Zentraxa, specialising in synthetic biology research, including cell therapies, new vaccine candidates, biosensing technology and bioengineering pharmaceuticals respectively. Their combined successes have led to millions of pounds of translational funding from angel investors and venture capitalists, overseen by Dr David Tew.
Lessons from Transforming UK Translation:
How to attract, train and retain the right talent was an important take-away message from the conference. Currently, collaborations rely heavily on personal networking to enable industry-academia interactions. There is a need to hire full-time ‘connectors’ to create an obvious digital ‘gateway’ that either party can contact. Also, encouraging the mobility of people between academia, start-up companies, industry and incubators will benefit the innovative ecosystem function with less conflict and more healthy competition. To incentivise academics to innovate, Universities need to recognise knowledge share and transfer of technology as a positive output.
As well as negotiating intellectual property of academics, cultivating long-term, trusting relationships is of equal importance. The amount of student industrial placements, sponsored PhDs and apprenticeships should be increased to build healthy business partnerships. A thriving knowledge economy should be the goal of businesses and academics, and all parties should encourage the sharing and application of ideas beyond the academic setting wherever possible.
Finally, it’s important not to consider translation as commercialisation alone. Translation does not revolve only around the spinout of companies through innovative ideas- long-term professional partnerships are just as significant. We should propel the collaborations between technology-driven companies and academic institutions, using the innovative ability of the former and the research of the latter in a way that both sides may sustainably benefit.
