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.
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.
Hosted by Dr Thomas Gorochowski and PhD students Veronica Greco and Matthew Tarnowski from the Biocompute Lab.
Dr Bert Poolman, a biochemist from the University of Groningen, visited Bristol on the 4th September to pose the question of whether it is possible to artificially create and control the physicochemistry of a cell. The ability to manipulate, control, or even create a new cell from scratch are fundamental directions for synthetic biology research.
What if we could build a cell in the lab?
Bert Poolman is part of an EU-wide project – aptly named BaSyC, or, ‘Building a Synthetic Cell’, which emerged in September 2017 combining leaders in physics, chemistry and biology from across the Netherlands to test out this theory.
“In the next decade they aim to achieve a physicochemical homeostatis in a cell where metabolic pathways and energy consumption/production systems can be better understood, optimised and synthetically built.” Veronica Greco explains. She was in the audience during his seminar.
Matthew Tarnowski, who also attended the seminar, said that Bert “highlighted some fascinating properties of cells: they are incredibly crowded, yet molecules move surprisingly fast within them.” Matthew was struck by Bert’s results demonstrating the sheer complexity of cells. “He [Bert] showed that engineering systems that mimic fundamental cellular processes is challenging”.
What was the audience reaction?
Intrigued audience members questioned the sustainability of such an ambitious project, such as how to overcome the challenge of building a synthetic ribosome and the new methods required to carefully assemble the numerous parts of a synthetic cell in a controllable way.
“The talk left me curious about how minimal life research could be completed responsibly: have the economic, social and environmental impacts been anticipated?” Matthew pointed out that the purpose behind building minimal forms of life went unanswered.
Veronica ended by noting that, “Overall, it is a very well thought out project that will require lots of different expertise and time, and surely it has all the credentials to give a big contribution to science and to change once again how the growing scientific field of synthetic biology is perceived.”
Are you a PhD or Postdoc?
BaSyC are offering various work packages to PhDs and Postdocs within one of their partner institutions. Due to the interdisciplinary nature of the work (combining physicists, chemists and biologists), “working at different locations and labs is more the rule than the exception”. There are opportunities to be involved in BaSyC activities: progress meetings and trainings, summer schools and the biennial international symposium on Building a Synthetic Cell.
No jobs available for the specific part of the programme you are interested in? Feel free to send an open application to the corresponding PI directly – the PI’s contact details can be found at their people page.
Questions: Matter to Life: Assembly of Synthetic Cells | Joachim Spatz, Max Planck Institute for Medical Research, Germany
Professor Stephen Mann, University of Bristol | Synthetic Protobiology
SBUK 2018 audience enjoy the ground-breaking sessions
Questions: Combining TAR cloning and CRISPR/Cas9 editing for the discovery of natural products from silent bacterial gene clusters | Christopher Corre, University of Warwick, UK
Questions: The genome design suite: Oliver Chalkley, University of Bristol
Questions: Applications of Synthetic Biology in Metabolic Engineering | Brian Pfleger, University of Wisconsin USA
Poster sessions provided networking opportunities at SBUK 2018
Questions: Nature-Inspired Polymer Synthesis | Tanja Weil, Max Planck Institute
Tanja Weil | Max Planck Institute of Polymer Research Germany | Nature Inspired Polymer Synthesis
Cellulose absorbent media to capture micropollutants | Amanda You - Customem Ltd, UK
Questions: Buckling of epithelium growing under spherical confinement | Aurelien Roux, University of Geneva, Switzerland
Questions: Towards a complete and quantitative view of genetic circuit function | Thomas Gorochowski, University of Bristol
Session six | Reporter systems for metabolic load and stress in Bacillus subtilis & Escherichia Coli | Wendy Smith, Newcastle University
Audience engagement during Wendy Smith's talk | Newcastle University
Questions: Synthetic Proteins for Synthetic Biology | Lynne Regan, University of Edinburgh
Animated discussions during poster sessions on Tuesday November 20th.
Questions: Unravelling the role of ß-catenin dynamics in mouse embryonic stem cell (mESC) identity | Elisa Pedone - University of Bristol
Questions: Matter to Life: Assembly of Synthetic Cells | Joachim Spatz, Max Planck Institute for Medical Research, Germany
Towards a complete and quantitative view of genetic circuit function | Thomas Gorochowski, University of Bristol
Professor Stephen Mann | University of Bristol | Synthetic Protobiology
Full details here
SBUK is the premiere UK synthetic biology meeting, bringing together all flavours of synthetic biology to foster a cohesive, vibrant and multidisciplinary community that is inclusive, open to innovation, collaboration and supportive of young talent.
