BBSRC’s sLoLa programme announces funding for project involving BBI Director

The Director of the Bristol BioDesign Institute, Prof Dek Woolfson, will be leading the University of Bristol’s contribution to one of five projects funded through the BBSRC’s strategic Longer and Larger (sLoLa) grants programme, which supports “adventurous fundamental bioscience research at the frontiers of human knowledge”.

The Universities of Bristol and Edinburgh are collaborating on the Enzymatic Photocatalysis project, which will be led by Prof Nigel Scrutton at University of Manchester. This project will “apply a cyclical design-build-evaluate-learn approach to discovering the generalisable principles of photo-biocatalysis.”

The Bristol team will design completely synthetic proteins that trap light and funnel this energy into new enzyme-like activities for generating molecules that are otherwise difficult to make synthetically or biochemically.

Anike Te appointed Aegis Professor of Engineering Biology 

Portrait photo of Anike TeAnike Te, Chief Strategy Officer for international materials company Lucideon, has joined the Bristol BioDesign Institute as an Aegis Professor in Engineering Biology. This prestigious appointment strongly aligns with our vision to be leading innovators in biomolecular and biosystems design and their translation, and for Bristol to be an internationally recognised centre in engineering biology.

Anike has experience in identification and adoption of new technologies into industry in healthcare, energy, construction, aerospace and ceramics in an international context. She has recently focused on the potential of synthetic biology to unlock sustainable, next generation materials.

Anike has also accepted a position on the Scientific Advisory Board for our UKRI-funded Bristol Centre for Engineering Biology, BrisEngBio, which was established to accelerate the translation of discovery synthetic biology research to address global challenges and boost the UK’s bioeconomy.

Anike will work across our portfolio of synthetic and engineering biology projects, surfacing and supporting the translation of novel therapeutics, diagnostics and materials. She will advise on the growth of our industrial networks to include new industries and new geographical regions, and mentor our new entrepreneurs.

The Aegis Professorship scheme was set up by the Science Partnership Office at the University of Bristol. In the scheme, visiting professors, who are leaders in their professional field, bring their up-to-date experience of work into academia. Through guidance and mentorship they facilitate joint working between researchers and external organisations such as industry and government.

Carmen Galan, Professor of Organic and Biological Chemistry and BrisEngBio Co-Lead for Innovation and Partnerships, said: “Working with Anike is a clear statement of our intention to work with industry to accelerate the translation of discovery synthetic biology research for real world benefit. The networks and expertise that Lucideon unlock for us aligns closely with our newest Bristol BioDesign Insititute research theme in Engineering Living and Sustainable Composite Interfaces.”

Imre Berger, Professor of Biochemistry and BrisEngBio Co-Lead for Innovation and Partnerships added: “Anike’s extensive expertise in establishing and leading international industrial networks will be a vital asset to accelerate new and potentially highly valuable projects that could evolve into transformative spin-outs and impacts. Having an external senior industrialist dedicate time to translation of research technologies is extremely valuable and Anike will be a perfect fit for this.”

Commenting on her appointment, Anike said: “It is a great honour to join the University of Bristol as an Aegis Professor in Engineering Biology. It’s a great opportunity to bring together academia and industry in an innovative, collaborative approach.”

“Lucideon is becoming increasingly involved in synthetic and engineering biology. It’s a very exciting area of science, which touches on many industries and technologies, and creates solutions to real-world issues, both in the UK and internationally.”

De novo designed peptides for cellular delivery and subcellular localisation

The Dodding (Biochemistry), Savery (Biochemistry), and Woolfson (Biochemistry and Chemistry) groups have teamed up with Birte Hoecker’s lab in Bayreuth, Germany to design peptides that smuggle functional cargoes into human cells.

They have used these designer cell-penetrating peptides to take control of a molecular motor and to ferry organelles from the middle to the periphery of the cells.

Their paper about this research was published in Nature Chemical Biology in July 2022.

  • De novo designed peptides for cellular delivery and subcellular localisation
    Guto G. Rhys, Jessica A. Cross, William M. Dawson, Harry F. Thompson, Sooruban Shanmugaratnam, Nigel J. Savery, Mark P. Dodding, Birte Höcker & Derek N. Woolfson
    Nat Chem Biol (2022). https://doi.org/10.1038/s41589-022-01076-6

‘Impossible’ protein-like structure made by University of Bristol researchers

The Woolfson (Chemistry and Biochemistry) and Clayden (Chemistry) groups have teamed up to make a new protein-like structure previously thought impossible. The work is reported in an article published in the journal Nature

Most proteins are built from two structural building blocks – the alpha helix and the beta strand. These can be combined in different ways to generate an amazing gallery of 3D shapes that give natural proteins their many functions. Other structural building blocks do exist, but they are rare and thought not to be overly important in protein structure or function. One of these is called the 310-helix. 

Uninhibited by the natural precedent for using alpha helices and the beta strands, and working between the two labs, Dr Prasun Kumar designed a protein-like molecule made solely from 310-helices. To do this, Prasun combined amino acids – the chemical units of proteins – that are found in natural proteins with others that are not. He made these designer proteins by chemical synthesis and showed that they formed bundles of pure 310-helices using X-ray crystallography.

The team now plans to probe this so-called “dark matter” of protein structure to explore chemistries and functions that go beyond those of natural proteins.        

The work is funded by the BBSRC, supported by BrisSynBio, and involved a collaboration with Dr Neil Paterson at the Diamond Light Source

Prof Imre Berger elected Fellow of Academy of Medical Sciences

Imre BergerImre Berger, Professor of Biochemistry and Chemistry, Co-Director of the Bristol BioDesign Institute, and Director of the Max Planck Bristol Centre for Minimal Biology, has been elected as a Fellow of the Academy of Medical Sciences for his outstanding contributions to biomedical science and notable discoveries during the COVID-19 pandemic.

This year, the Academy has elected 60 outstanding biomedical and health scientists to its Fellowship for their remarkable contributions to biomedical and health science and their ability to generate new knowledge and improve the health of people everywhere.

Professor Berger’s work includes a number of significant breakthroughs in the fight against COVID-19. His team discovered a druggable pocket in the SARS-CoV-2 Spike protein that could be used to stop the virus from infecting human cells, blocking transmission and forestalling severe COVID-19 disease. At the height of the pandemic, his team showed that exposing the SARS-CoV-2 coronavirus to a free fatty acid called linoleic acid locks the Spike protein into a closed, non-infective form inhibiting the virus’ ability to enter and multiply in cells, stopping it in its tracks.

The findings, published in Science, are now being used to develop new cost-effective treatments against all pathogenic coronavirus strains by Bristol-based Halo Therapeutics Ltd. The biotech company, co-founded by Professor Berger, is currently preparing for in-human clinical trials.

Other notable breakthroughs include the discovery that SARS-CoV-2-infected individuals could have several different SARS-CoV-2 variants hidden away from the immune system in different parts of the body, which may make complete clearance of the virus from infected persons, by their own antibodies, or by therapeutic antibody treatments, much more difficult.

Professor Berger is also pioneering new vaccine technologies. His team developed the ADDomer™, a thermostable vaccine platform for highly adaptable, easy-to-manufacture, rapid-response vaccines to combat present and future infectious diseases including COVID-19.  A key benefit of the platform is the speed with which candidate vaccines can be identified and could be manufactured in large quantities without refrigeration, significantly facilitating distribution world-wide. Vaccine innovator start-up Imophoron Ltd, co-founded by Professor Berger, is bringing ADDomer™-based vaccines to the market.

Professor Imre Berger said: “I am honoured to have been elected to the Fellowship of the Academy of Medical Sciences.

“I am also deeply grateful for the great effort by the fantastic scientists, technicians, engineers and students in my team, past and present, and the collaborators whom I have the privilege to work with. As researchers, the pandemic has presented us with immense challenges which has only highlighted the importance of scientific endeavour and medical science. It is therefore rewarding to have had our contributions recognised by the Academy that also seeks to improve and support advances in this field.”

Professor Dame Anne Johnson FMedSci, President of the Academy of Medical Sciences said: “Each of the new Fellows has made important contributions to the health of our society. The diversity of biomedical and health expertise within our Fellowship is a formidable asset that in the past year has informed our work on critical issues such as tackling the COVID-19 pandemic, understanding the health impacts of climate change, addressing health inequalities, and making the case for funding science. The new Fellows of 2022 will be critical to helping us deliver our ambitious 10-year strategy that we will launch later this year.”

The new Fellows will be formally admitted to the Academy on Monday 27 June 2022.

(This news story was originally published by the University of Bristol)

BrisEngBio, the new Bristol Centre for Engineering Biology, launched

Simeon Castle holding petri dishes in the lab
Simeon Castle, SynBio CDT PhD Student. Photo by Felix Russel-Saw

A new centre for engineering biology will build on Bristol’s success in synthetic biology and accelerate translation of its pioneering research to address global challenges and boost the UK’s bioeconomy.

By applying engineering principles to living systems, engineering biology aims to solve some of the world’s most pressing challenges in health, food security, and the environment.

The Bristol Centre for Engineering Biology, BrisEngBio, brings together scientists from a wide range of disciplines – from biology and chemistry to data science and systems engineering. Partnering with deep tech incubator, Science Creates and Oracle for Research, the aim is to develop fundamental research discoveries into commercially viable applications that benefit people and the planet.

BrisEngBio is the evolution of the UKRI-funded Synthetic Biology Research Centre, BrisSynBio, which published more than 325 research papers, enabled the spin-out of eight biotech companies, and leveraged additional research funding of over £90M.

“BrisEngBio embodies the same spirit of discovery and entrepreneurship that made BrisSynBio one of the country’s most academically and commercially successful centres for synthetic biology. Through this, we have already demonstrated that our fundamental research discoveries can be made commercially relevant. Now, through BrisEngBio, we are putting the ecosystem in place to really accelerate both discovery science and its translation.

“BrisEngBio’s early-career researchers will be honorary members of Science Creates, and through this they will benefit from a bespoke training and mentoring programme in innovation and commercialisation,” said Professor Dek Woolfson, Principal Investigator and Director of BrisEngBio.

“It’s been fantastic to work with many of the spin-out companies that came from BrisSynBio through Science Creates, with Science Creates Ventures having led investment rounds totalling £7.5 million and directly invested in two of those companies Imophoron and Cytoseek. We look forward to building on those successes, continuing our partnership with the University, and enabling more of these important discoveries to be translated for global good,” said Dr Harry Destecroix from Science Creates.

Photo of Dr Thomas Gorochowski, Dr Lucia Marucci and Professor Dek Woolfson
BrisEngBio investigators Dr Thomas Gorochowski, Dr Lucia Marucci and Professor Dek Woolfson at the BrisEngBio launch event. Photo by Beeston Media

“Synthetic and engineering biology has enormous potential to address some of the major global challenges that we face today.  For example, in healthcare, energy and food security.  But this requires input from all areas of science. BrisEngBio is a truly multidisciplinary venture, involving 55 University of Bristol academics from 11 Schools across four Faculties, and three Research Institutes,” said Professor Woolfson.

Initial UKRI funding of £1.5M will support 12 research projects and early career researchers over two years. BrisEngBio will cross disciplines to develop truly novel research such as hijacking bacterial transport as an antimicrobial strategy; identifying novel natural products for drug discovery; and using machine learning to predict self-healing properties of biohybrid materials.

Aligned with the UK Government’s National Engineering Biology Programme (NEBP), the centre promises to strengthen the UK’s position as an international leader in biotechnology.

Co-Investigator Dr Thomas Gorochowski said: “BrisSynBio had unprecedented success in funding and nurturing the fundamental science behind synthetic biology. It is critical that centres like ours set the research agenda and help maintain the UK’s position at the forefront of synthetic biology. BrisEngBio will provide the ecosystem to drive translation of new discoveries into commercially viable and truly world-leading engineering biology.”

Collaborating with Oracle for Research, BrisEngBio will utilise advanced cloud computing to realise data-driven design that combines academic and industry expertise in data science, machine learning, and multi-scale modelling.

Alison Derbenwick Miller, Vice President, Oracle for Research, said: “We are delighted that Oracle Cloud technology can support next-generation discovery and innovation at the new Bristol Centre for Engineering Biology (BrisEngBio). Through our collaboration, Oracle for Research will continue to support University of Bristol projects that drive real change through discovery and accelerate important research.”

Co-Investigator Dr Lucia Marucci said: “This is such an exciting time to be working at the interface of the natural sciences and engineering. We have seen through the pandemic what impact synthetic biology can have on our ability to develop vaccines and treatments. At BrisEngBio, we will nurture early career researchers and help them transition their research from scientific discovery to solutions that are both commercially viable and have the potential to address some of our most pressing global challenges.”

Professor Wolfson said: “I am delighted and excited by the continued support from UKRI and Government for the important area of synthetic biology. The new centre will allow us to translate our discoveries in fundamental synthetic biology into cutting edge technologies with significant impact locally, nationally and internationally, and across healthcare, the bioeconomy and environment.”

(This press release was originally published by University of Bristol on 29 March 2022)

Bristol’s pioneering COVID-19 research prompts French Embassy visit

Representatives from the French Embassy visited University labs on 10 December to see some of the innovative COVID-19 research being undertaken at Bristol, including work on ADDomer™, a thermostable vaccine platform being developed by Bristol scientists to combat emerging infectious diseases.

Dr Rachel Millet and Arthur Belaud from the Embassy’s Innovation Branch, which seeks to drive France-UK business enterprise, met with scientists Professor Imre Berger and Frederic Garzoni, founders of Imophoron Ltd, the biotech start-up developing ADDomer that uses technology developed at an institution in France, and recently secured £4 million investment.

L to R: Arthur Belaud from the French Embassy, Dr Anne Westcott from the University, Dr Rachel Millet from the French Embassy and Professor Imre Berger at the University’s Max Planck Bristol Centre for Minimal Biology.

During the visit, the delegation took a tour of labs in the University’s Max Planck-Bristol Centre for Minimal Biology (MPBC), the GW4/Wellcome Trust Cryo-EM facility led by Prof Christiane Schaffitzel, and Science Creates, the Bristol-based incubator, which is operated in partnership with the University and supports scientists and engineers in commercialising ground-breaking innovations. Having recently opened its second facility in the city’s Old Market, the party met with Science Creates founder and Bristol graduate Dr Harry Destecroix to discuss the future of deep-tech eco-systems.

Professor Imre Berger, Director of Bristol’s Max Planck Centre for Minimal Biology, said: “We are honoured to host this visit from the French Embassy’s Innovation Branch to share knowledge and showcase the pioneering research that is being done in collaboration with our European colleagues and institutions.”

Press release issued: 10 December 2021 on University of Bristol News and Features~ article here.

Bristol innovators to administer thermostable COVID vaccine in clinical trials

CEO of Imophoron Ltd, Frederic Garzoni, and University of Bristol researchers, including Imophoron co-founder Professor Imre Berger, combine efforts to generate a promising vaccine candidate for COVID19.

Professor Imre Berger (left) and Frederic Garzoni (right) at the Life Sciences Building at the University of Bristol

Prior to the pandemic, Frederic Garzoni and Imre Berger bolstered their research in a synthetically engineered protein scaffold named ADDomer™, and with Oracle’s cloud computing technology and Cryo-Electron microscopy (Cryo-EM), the protein was found to be thermotolerant. Professor of Biochemistry, Christiane Berger-Schaffitzel, who was leading the Cryo-EM team, said that “seeing Fred’s vaccine design [at near atomic resolution] in such detail gave us confidence that we were on the right track”.

The protein’s novel ability to maintain its structural integrity without refrigeration, even for months on end, eliminates the cold chain problem that all other mRNA based vaccines are constricted to. To compare, COVID vaccines by AstraZeneca, Moderna and BioNTech need to be cooled at 4°, -20° or even -80°, which restricts their transportability to remote locations.

The protein contains a druggable ‘pocket’ in its surface, which can be injected with various live-attenuated diseases. Professor Imre Berger explains that the body then develops a strong immune response against the “small and harmless pieces of the virus on top of the surface of the ADDomer™”.

First tested on emerging infectious arbovirus, Chikungunya, the vaccine candidate can be used boost antibodies against a host of other viruses and diseases. Spurred on by the success of antibody development in animal models, the Cryo-EM work, accelerated by Oracle Cloud, was instrumental in fast-tracking the vaccine design with other viruses in its ‘pocket’. Today, Imophoron Ltd has secured a £4 million investment to accelerate three vaccines to clinical trials on humans; Chikungunya, RSV (respiratory syncytial virus), and COVID19.

When the first lockdown hit in 2020, a group of clinicians, virologists, chemists, biologists and other academics mobilised as the University COVID19 Emergency Research (UNCOVER) group to tackle the global health crisis. “Scientists everywhere mounted an unprecedented effort to decipher SARS-CoV-2 and the disease, in record time” says Adam Finn, UNCOVER lead and Bristol Professor of Paediatrics. UNCOVER labs urgently needed SARS-CoV-2 antigens to create tests to detect antibodies in the blood of people who had contracted the virus.

SARS-COV-2 virus image (left) and ADDomer™ COVID vaccine image (right)

Fred Garzoni volunteered to assist UNCOVER with supplying the reagents they needed, having worked closely with Bristol researchers Berger and Berger-Schaffitzel on ADDomer™. This was also a unique opportunity to test Imophoron’s protein scaffold technology and develop, as fast as possible, a thermotolerant COVID-19 vaccine candidate with the protein. Within weeks, a viable vaccine had been developed for use on animals in preclinical tests.

“We had access to everything and everybody through UNCOVER” said Fred Garzoni, who worked tirelessly with the Vet School and the ASU’s UNCOVER researchers including Mick Bailey, Jamie Mann, Joe Roe, and David Morgan. Their trials on animal models showed incredibly promising results. Not only did the COVID-19 vaccine candidate induce strong immune responses in subjects, but it critically interrupted virus transmissibility.

In addition, the vaccine may not need trained healthcare professionals to administer the dose. The vaccine was just as effective when administered intranasally as with a syringe, which would reduce the cost and complexity of rolling out worldwide pandemic vaccine programmes. In theory, you could self-administer the COVID vaccine as a nasal spray at home!

The distinctive features of this vaccine candidate – its thermostability and various methods it can be administered- truly set the ADDomer™ apart from existing vaccines. Now that the global uptake of the COVID vaccine stands at 47%, this discovery made by Imophoron Ltd and UNCOVER at the University of Bristol could truly transform the accessibility of vaccines to the most remote corners of the world.

BBI Spin-out Zentraxa showcased in UK Innovation Strategy

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!