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.
Overview
Two BBSRC-funded post-doctoral research associate positions are available immediately to work in Dek Woolfson’s Peptide Design and Assembly group in the Schools of Chemistry and Biochemistry at the University of Bristol. Experience in one or more of peptide chemistry, protein biochemistry, de novo peptide/protein design, and the structural characterization of peptides and proteins would be an advantage. However, such experience is not essential, as we are looking for enthusiastic and talented researchers in the chemical/biochemical sciences who are interested in pursuing careers in peptide/protein design and its application in chemical and synthetic biology.
Post 1: De novo protein design in cells
This three-year post is joint with Dr Mark Dodding’s group (Biochemistry, Bristol). It builds on recent work between the Woolfson and Dodding groups (Cross et al.Cell Chem Biol(2021) DOI: 10.1016/j.chembiol.2021.03.010; Rhys et al.Nature Chem Biol(2022) DOI: 10.1038/s41589-022-01076-6). The project aims to design motor proteins from the bottom up to operate in eukaryotic cells.
Environment The Woolfson lab has purposed-built office space for computational work and laboratories for peptide chemistry, protein biochemistry, biophysics, protein crystallization, and cell biology. In addition, through Chemistry, Biochemistry, and the Bristol BioDesign Institute, the group has walk-up access to mass spectrometry, light and electron microscopy, and other facilities. The current group comprises 16 people with a balance of PhD and post-doctoral researchers from diverse backgrounds from around the world, which fosters a supportive, inclusive, and cutting-edge approach to peptide-design research.
Anike 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.”
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
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.
As part of City Nature Challenge 2022, a team of PhD candidates at the University of Bristol have led hands-on, family-friendly public engagement activities explaining how the cutting edge science of environmental DNA (eDNA) sequencing can be used to identify local wildlife. DNA sequencing has been taking place in universities and research labs for half a century, but the Bento Lab – a portable, hand-held DNA lab – is allowing citizen scientists to study the DNA of living things around them. The University of Bristol team used a series of escape room-like activities to bring to life the processes involved in using the Bento Lab.
The activities took place in Queen Square, Castle Park and Tyntesfield in Bristol, and were led by (l-r) Matt Tarnowski, Claire Noble, Hannah Langlands, Harry Thompson and Rosie Maddock.
An activity introducing the microscopic world of biology at our fingertips
DNA can be collected from inside an organism’s cells in a process that is a bit like popping a balloon. This was the first task to participants had to do – the balloon had been filled with the letters G, T, C, A to represent DNA – and they then extracted the ‘DNA’ using a pipette. As it is hard to study DNA from so few cells, a polymerase chain reaction (PCR) is used to amplify a particular DNA sequence within the cells. Attendees had to figure out how the PCR process works using coloured dominoes, and all succeeded in understanding that it involves repeatedly doubling the targeted DNA.
This amplified DNA can be selected using gel electrophoresis, which was demonstrated using a noisy rain-stick. The final step is sequencing the DNA, and participants enjoyed donning a cape to give them the ‘superpower’ of being able to read DNA. Since these lab tasks would take hours with the Bento Lab, environmental samples that were brought along were taken away for identification, and attendees will be notified of their species once analysed.
Interactive activities brought eDNA sampling, PCR, the Bento Lab & DNA sequencing to life (l-r)
Putting the mobile eDNA lab to the test
Some creatures, such as fungi or microorganisms, can be hard to spot, yet play essential roles in the environment. The next stop for the Bento Lab is to assess fungal diversity at a site of ecological restoration. The Refungium at Coed Talylan in Wales aims to foster the highest diversity of fungi in the UK. The Refungium will be a refuge for native mushrooms, and studying the fungi there with the Bento Lab will inform restoration of this 15-hectare semi-natural woodland.
Would you like to host the eDNA lab?
We welcome opportunities to share this portable workshop, be it at a school, college, university or festival. With activities for all ages, this citizen science experiment has the potential to inspire the next generation of bioscientists and stewards of the environment. As well as learning how eDNA studies work, it opens up conversations about genetics, synthetic biology, ecology, microbiology, sustainability, climate change and responsible research. These themes mesh with the sustainability and climate change strategy recently shared by the UK’s Department for Education. If you would like to host the eDNA lab, please write to us.
Matthew Tarnowski, Claire Noble, Hannah Langlands, Rosie Maddock and Harry Thompson developed this project, which was funded by the EPSRC/BBSRC Centre for Doctoral Training in Synthetic Biology (SynBio CDT) Outreach Award.
Imre 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.
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.
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.”
PhD candidates Matthew Tarnowski and Harry Thompson are embarking on a short project attempting to develop a high sensitivity biosensor to identify individual species of bacteria in river water samples. This biosensor will be built using the SHERLOCK CRISPR-based technology, which has already been applied to a variety of tasks ranging from diagnosing ZIKA virus infection in patient samples to fish species identification. As avid wild swimmers, Harry and Matt are hopeful that this could be a useful tool in clarifying the safety of water to swim in. Ideally, the biosensor would enable the rapid identification of microbial species in rivers and other waterways used for swimming/recreation.
Matt said: “Water is like a glue that binds ecosystems: hydrating and connecting them through the microbial life it sustains. We seek to detect microorganisms which indicate healthy and unhealthy water.”
Harry added: “In our preliminary studies, we hope to generate initial results which show that the biosensor can reliably detect a single species in a mixture of microorganisms in the lab. We will also test samples from popular swimming and spring water locations and no doubt do a bit of wild swimming too.”
Biosensors can detect microorganisms in water that are invisible to the naked eye
The underpinning technological basis for this project is the SHERLOCK platform (specific high-sensitivity enzymatic reporter unlocking). This technology allows rapid (around 1h) and reliable detection of nucleic acids at concentrations as low as 1 molecule DNA per millilitre (zeptomolar).
This project involves a novel application of SHERLOCK: biosensing of microbes in water. The SHERLOCK technology has been previously demonstrated to work also as a lateral flow (LTF) based assay and developing the biosensor for LTF use would form the basis of any follow-on work.
Such a device could be used for simple, rapid assessment of swimming water by anyone, anywhere.
Imre 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.
