NRP biotech spin-out Iceni Diagnostics wins Business Award

NRP based biotech company, Iceni Diagnostics, which is a spin-out from John Innes Centre and University of East Anglia has won a prestigious award that celebrates the best businesses in the region.

The long standing EDP Business Awards recognised the achievements of the Norwich Research Park based company with the Knowledge Catalyst award.

It was one of thirteen awards handed out to businesses from all over the county.

The theme of the 2017 awards was “Innovation”, a quality demonstrated by winners from diverse areas including artificial intelligence and medical diagnostics, through to tourism and construction.

Iceni Diagnostic are developing a device designed to detect microbial and viral pathogens. It is hoped that this simple colour-change test will allow rapid diagnosis, improve decision making, and potentially reduce the unnecessary prescription of antibiotics.

Professor Rob Field, co-founder and CEO of Iceni Diagnostics and a project leader at the John Innes Centre said, “It’s great to be recognised for doing something that we’re passionate about. We work to take fundamental scientific understanding and apply it to real world problems, in this case reducing our dependence on antibiotics.”

The EDP Business Awards are aimed at ambitious businesses and organisations that are underpinned by the acquisition, implementation, and exchange of knowledge.

The judges look for a sustained commitment to acquiring and embedding new ideas within their business planning and structure.

From JIC News pages.

Landmark discovery turns marathon of evolution into a sprint

A research collaboration has discovered a new way of rapidly generating a swathe of medically significant natural products after discovering a ground-breaking technique that turns the marathon of evolution into a sprint.

The surprise discovery came when the research team inadvertently replicated a process that bacteria use to evolve their machinery for making natural products.

Now the team, which includes scientists at the John Innes Centre, plan to harness this process to generate “libraries” of valuable compounds created from the technique which they have named Accelerated Evolution.

“For 20 years we have been using rational bioengineering to modify the chemical structures of clinically important natural products – using genetics to make a new molecule in a process that parallels medicinal chemistry – and that’s what we were doing when we stumbled upon this,” said Professor Barrie Wilkinson from the John Innes Centre.

“We have discovered a completely new way of doing things, one that will also teach us how to better bioengineer systems in a rational manner.”

The collaboration was led by Isomerase Therapeutics Ltd, and included the University of Cambridge, Pfizer, Roche and DSTL.

The team were involved in lab work to produce new versions of rapamycin, a commercially successful natural compound produced by bacteria, used to prevent organ transplant rejection and treat certain cancers.

Rapamycin belongs to a medically and agriculturally important class of compounds called Polyketides. Fungi and bacteria produce these compounds to give them a survival advantage, for example to defend against pathogen attack and secure resources in the environment.

As part of their experiment, the team inserted a temperature sensitive replicon into the genome of the host strain, the soil bacteria Streptomyces rapamycinicus.

But instead of the expected result – a new Streptomyces rapamycinicus strain producing a specific new version of rapamycin – they isolated a wide range of new strains that each produced unexpected new molecules. These strains could be further modified leading to hundreds of new, structurally diverse compounds.

The team believe that, by inserting the replicon into the genes responsible for making rapamycin, they inadvertently introduced a genetic instability which activated a DNA repair process called homologous replication.

This caused the host bacteria to “spit” out the replicon from the genome, causing a rearrangement of the rapamycin biosynthetic genes.

Professor Wilkinson explains: “We think this process mimics and accelerates the processes that are prevalent during natural polyketide evolution.”

By setting up a drug discovery development platform to harness the Accelerated Evolution platform, the team believes it is at the beginning of a new age in natural product drug discovery.

Dr Matthew Gregory, a corresponding author of the paper and CEO of Isomerase Therapeutics Ltd, said:  “The work described in this paper has important ramifications for the natural products field and synthetic biology generally.”

The discovery is outlined in the journal Nature Communications in a paper called: Diversity oriented biosynthesis via accelerated evolution of modular gene clusters.

Plant-produced polio vaccines could help eradicate age old disease

Plants have been used to produce a new vaccine against poliovirus in what is hoped to be a major step towards global eradication of the disease.  A team of scientists, including Dr Johanna Marsian working in Professor George Lomonossoff’s Lab at the John Innes Centre, has produced the novel vaccine with a method that uses virus-like particles (VLPs) – non-pathogenic mimics of poliovirus which are grown in plants.  Genes that carry information to produce VLPs are infiltrated into the plant tissues. The host plant then reproduces large quantities of them using its own protein expression mechanisms.

Professor Lomonossoff, from the John Innes Centre said: “This is an incredible collaboration involving plant science, animal virology and structural biology. The question for us now is how to scale it up – we don’t want to stop at a lab technique.”

VLPs look like viruses but are non-infectious. They have been biologically engineered so they do not contain the nucleic acid that allows viruses to replicate. This means that they mimic the behaviour of the virus, stimulating the immune system to respond without causing an infection of poliomyelitis.  Laboratory tests demonstrated that the poliovirus mimics provided animals with immunity from the disease paving the way for human vaccines to be produced by plants on a major scale with the input of pharmaceutical industry collaborators.  The breakthrough was made by a consortium funded by the World Health Organisation (WHO) which is seeking to eradicate a disease that has been known since antiquity.  The WHO is seeking alternative vaccines that avoid use of the live virus as part of an international drive to completely eradicate the virus worldwide.

A global scourge up to the middle of the last century, poliovirus has been reduced by 99% since 1988 due to the Global Polio Eradication Initiative led by the WHO. Current polio vaccines, however, require the production of huge quantities of the virus. Using the live virus not only represents a risk of the virus escaping, the use of the live attenuated (weakened) virus, effectively maintains polio in the global population.

VLPs were expressed at the John Innes Centre using Hypertrans® transient plant expression system which had previously been developed there. This successful development not only holds promise for the production of vaccines for polio: it could become a frontline diagnostic resource in producing vaccines against other viral outbreaks.

“The beauty of this system of growing non-pathogenic virus mimics in plants, is that it boosts our ability to scale-up the production of vaccine candidates to combat emerging threats to human health,” said Prof Lomonossoff.

A = VLPs in vitreous ice. B = Reconstruction of poliovirus. C = VLP showing empty internal surface. D and E = Views of poliovirus molecular structure

In the past 20 years plants have become serious competitors to bacteria, insect cells, yeast or mammalian cells as production systems for pharmaceutical materials. They are cost-effective requiring simple nutrients, water, carbon-dioxide and sunlight for efficient growth and the transient expression system can be adjusted rapidly with low costs.  The work at the John Innes Centre furthered work of scientists at the University of Leeds, who first discovered a way of producing the virus-like particles (VLP) using the Hypertrans® expression system.  Despite successes of plant-based expression to produce VLPs of papilloma and hepatitis B viruses, poliovirus VLPs had previously proved too unstable to make practical vaccines using this technique. A problem is that the genetic material which causes replication of the virus and which is therefore absent from the VLPs, also has a role in holding the particles together.

However teams from The National Institute for Biological Standards and Control, and the University of Leeds identified mutations within protein coats which enabled the production of VLPs which are sufficiently stable to act as vaccines. Experiments at the University of Oxford showed that these were identical to native poliovirus retaining their shape when warmed, and which are effective in protecting animals against poliovirus.

The team used cryo-electron microscopy at Diamond Light Source’s Electron Bio-Imaging Centre (eBIC) to obtain a clear look at the structure of the VLPs. They confirmed the structure and showed that the external features of the particles were identical to those of poliovirus.  Dave Stuart, Director of Life Sciences at Diamond and Professor of Structural Biology at University of Oxford said, “We were inspired by the successful synthetic vaccine for foot-and-mouth disease, also investigated at Diamond as part of UK research collaboration. By using Diamond’s visualisation capabilities and the expertise of Oxford University in structural analysis and computer simulation, we were able to visualise something a billion times smaller than a pinhead and further enhance the design atom by atom of the empty shells. Through information gained at Diamond, we also verified that these have essentially the same structure as the native virus to ensure an appropriate immune response.”

This collaboration means manufacturing the particles stabilised in plants on a large scale as precursors to vaccines is now much closer to becoming a reality. The results are outlined in the journal Nature communications: Plant-made Polio 3 stabilised VLPs – a candidate synthetic Polio vaccine.

The collaboration includes the John Innes Centre, The National Institute for Biological Standards and Control, Oxford University, University of Leeds, Diamond Light Source, the Henry Wellcome Building for Genomic Medicine.

Background information: Poliovirus: the scourge of summers past

An ancient Egyptian stone engraving provides a clue that the poliovirus has been a disturbing blight on our lives since antiquity. The 3,500-year-old engraving appears show a polio victim, a priest with a withered right leg. From then the virus was widely feared up until the middle of the last century and the arrival of the first effective vaccines. Polio is now down to a few hundred cases a year world-wide, but these numbers remain steady as the virus is maintained in the environment by the use of the live attenuated vaccine.

“The poliovirus is a very nasty disease and certainly until the 1950s was a real scourge.” said Professor George Lomonossoff of the John Innes Centre, based at Norwich Research Park.

“It was known as the summer plague and here in Norwich the main source of it was bathing in the river Yare near Earlham Park.”

“Most people had very mild symptoms but some people got paralytic polio and in worst cases couldn’t breathe properly and had to be put in an iron lung in order to breathe.”

Poliovirus is the causative agent of poliomyelitis which destroys motor neurons in the central nervous system causing paralysis or even death. Transmission is primarily by ingesting infected water. The Global Polio Eradication Initiative led by the World Health Organisation has resulted in 99 per cent fewer cases in the past 30 years by using two highly effective vaccines: the live attenuated (weakened) vaccine developed by Albert Sabin and the formaldehyde-inactivated or killed virus developed by Jonas Salk. Production of both vaccines, developed in the 1950s, requires propagation of large quantities of live poliovirus increasing the risk of accidental re-introductions. Because of this risk, the WHO has intensified its search for cheap and viable alternatives, this breakthrough using the virus-like particles presents an exciting new option. Virus free vaccines will allow polio to be eradicated, they will prevent recurrences without the risks associated with the using the live virus vaccines.

Press release from JIC website news

New study links antibiotic resistance to common household disinfectant triclosan

Scientists from the John Innes Centre, Quadrum Institute and the University of Birmingham have discovered a link between a major mechanism of antibiotic resistance and resistance to the disinfectant triclosan which is commonly found in domestic products.

Researchers made the unexpected finding that bacteria that mutated to become resistant to quinolone antibiotics also became more resistant to triclosan.

The scientists showed that the quinolone-resistance mutation altered the way the bacteria package their DNA inside a cell and that these mutants had also turned on various self-defence mechanisms – together these gave triclosan resistance.

Quinolone antibiotics are an important and powerful group of human medicines, and this new discovery raises concerns that the use of triclosan can give antimicrobial resistance.

The research, carried out at the Institute of Microbiology and Infection at the University of Birmingham in collaboration with the John Innes Centre and The Quadram Institute, was published today in the Journal of Antimicrobial Chemotherapy.

Corresponding author Dr Mark Webber, from the Quadram Institute and Honorary Senior Lecturer at the University of Birmingham, said: “We think that bacteria are tricked into thinking they are always under attack and are then primed to deal with other threats including triclosan.

“The worry is that this might happen in reverse and triclosan exposure might encourage growth of antibiotic resistant strains.

“We found this can happen in E. coli. As we run out of effective drugs, understanding how antibiotic resistance can happen and under what conditions is crucial to stopping selection of more resistant bacteria.”

Co-author Professor Laura Piddock, of the Institute of Microbiology and Infection at the University of Birmingham, said: “The link between quinolone and triclosan resistance is important as triclosan has become ubiquitous in the environment and even human tissues in the last 20 years”.

“Given the prevalence of triclosan and other antimicrobials in the environment, a greater understanding of the impact they can have on bacteria and how exposure to these antimicrobials may impact the selection and spread of clinically relevant antibiotic resistance is needed.”

Professor Tony Maxwell, from the John Innes Centre, said: “This work shows the power of combining the expertise from the different teams working in Norwich and Birmingham to achieve a better understanding of the mechanisms of antimicrobial resistance, which is a serious and increasing problem in the UK and elsewhere.”

In the last decade there has been an explosion in the marketing of products aimed at the home market labelled as ‘antimicrobial’.

There is also largely a lack of evidence for additional benefits of these products over traditional cleaning and hygiene products (e.g. bleach, soap and water).

There has, however, been concern raised that the active antimicrobial ingredients for some of these products are accumulating in the environment where they are altering ecosystems and potentially promoting selection of antibiotic resistant bacteria.

Triclosan, in particular, has been the cause for some concern which has led to a ban across the EU and now USA in its use in hygiene products (hand, skin and body washes). Many other antimicrobial agents are, however, still used in these products.

News item from John Innes News pages

Newly-discovered plant enzymes open the door to novel compound production

A wealth of previously undescribed plant enzymes have been discovered by scientists at the John Innes Centre. The team who uncovered the compounds hope that harnessing the power of these enzymes will unlock a rich new vein of natural products, including potential drug leads.

The research, published in PNAS reveals new insights into the bio-production of sesterterpenoids, a rare and largely unexplored class of chemicals. Prior to this work at the John Innes Centre the majority of the approximately 1,000 known sesterterpenoids have been found in terrestrial fungi and marine sponges, with only 60-70 from plants.

Previously, very little was known about how these compounds were made. A handful of enzymes that make sesterterpenoids had been discovered in fungi, but the enzymes that make plant sesterterpenoids were largely unknown.

The team led by Professor Anne Osbourn, used genome mining technology to uncover a suite of enzymes, called sesterterpene synthases by searching the genomes of 55 different plant species.

Professor Osbourn says, “What’s fascinating is that the enzymes from plants are quite different to those from fungi, but in some cases they make similar molecules. It looks as though plants have independently arrived at their own way of making these molecules; they have ‘worked it out for themselves’.”

The next step is to widen our search for genes that encode plant sesterterpene synthases in order to get a fuller picture of the spectrum of chemical diversity of sesterterpenoids in other plant species, and to harness these enzymes to make compounds that can be evaluated for use as new drugs and medicines.

The project will continue to use transient plant expression technology developed by Professor George Lomonossoff at the John Innes Centre in which plants can be used to produce a range of pharmacologically active proteins.

Professor Osbourn continues, “This is a flagship paper in terms of uncovering a swathe of new enzymes in plants to make chemicals that have never been accessed before.”

This work, which is funded by the US-based National Institutes of Health (NIH) as part of the Genomes to Natural Products Network, was carried out in collaboration with researchers at the University of Wageningen in the Netherlands, the University of Cambridge in the UK, and the University of California, Davis (US).

Decoding and recoding biological systems

The past few years have seen unprecedented advances in DNA sequencing and synthesis technologies. These technologies, in combination with sophisticated new methods of analysis, have opened up unprecedented opportunities to recode organisms to produce new bio-products which may support advances in medicine, agriculture or industrial processes.
A research workshop titled ‘Decoding and Recoding Biological Systems’ brought together scientists working across interdisciplinary interfaces spanning genomics, computational and synthetic biology and chemistry, providing a forum for enhanced interactions and collaborative research opportunities. There were presentations from speakers from across the Norwich Research Park as well as three invited external speakers, Dr Marnix Medema (University of Wageningen), Professor Jim Haseloff (University of Cambridge) and Dr Quentin Dudley (Jewett lab, Northwestern University).

Prof Neil Hall, the Director of the Earlham Institute (EI), kicked off the proceedings with an overview of the current state of play regarding genome sequencing technologies. Marnix Medema outlined computational approaches for natural product pathway discovery in microbes and plants. Andy Truman from the John Innes Centre (JIC) followed with an example of recoding of bacterial genes for the synthesis of the antibiotic bottromycin. Ray Dixon from the John Innes Centre presented work on modular approaches that he is taking to engineer nitrogen fixation in plants.

Amit Sachdeva from the School of Chemistry at the University of East Anglia (UEA) reported on how he is expanding the genetic code to enable the incorporation of non-native amino acids into proteins in order to modulate protein activity. The afternoon session focussed on research from Nicola Patron (EI), George Lommonossoff (JIC) and Jim Haseloff (University of Cambridge), who are all bioengineering plants in different ways (for food security, production of therapeutic proteins and vaccines, and for the development of model systems for fundamental research and training). The day ended with a lecture by Quentin Dudley (Jewett lab, Northwestern University, US) on using in vitro cell-free technology to produce plant natural products in a test tube.

Congratulations to Thomas Bridge (UEA), Anastasia Orme (JIC) and Roger Castell-Graells (JIC) who won prizes in the best science poster competition (1st, 2nd and 3rd respectively)

The Decoding and Recoding Biological Systems’ workshop was organised by Professor Anne Osbourn (JIC), Director of the Norwich Research Park Industrial Biotechnology Alliance. It was held in the Earlham Institute on Friday 19th May 2017.

Scientists discuss progress in decoding and recoding biological systems at the poster session

Discovering new antibiotics from ants

Bacteria which live on the surface of leaf-cutter ants discovered in the tropics produce an exciting array of antibiotics. These antibiotics are new to science and have exciting properties not found previously – including the ability to kill bacteria which are otherwise now resistant to other anitbiotics. The breakthrough results from research of Professor Matt Hutchings and his group in the School of Biological Science at UEA and collaboration with Prof Barrie Wilkinson in the Department of Molecular Microbiology at JIC. The results from these studies are described in highly accessible new webpages on UEA’s website via this link http://www.uea.ac.uk/research/brilli-ant.

Public join in hunt for new antibiotics in Thetford Forest soil

Visitors to High Lodge in Thetford Forest next week can join scientists from the University of East Anglia (UEA) who will be digging for clues in the race to solve the problem of antibiotic resistance, as part of the Microbiology Society’s ‘Antibiotics Unearthed’ project.

Antibiotics Unearthed is a crowd sourced science project, which members of the public can get involved in during a ‘pop up’ event in Thetford on Thursday, May 4, from 10am-4pm.

People visiting the Pop-Up Science Centre will help scientists search for new antibiotics by collecting and preparing a spoonful of East Anglian soil that will be sent off to UEA for analysis.

Prof Laura Bowater, from UEA’s Norwich Medical School, said: “Antibiotics are vital medicines used to treat bacterial infections. Most are made by soil bacteria, so people taking part in Antibiotics Unearthed can make a real contribution in our search for new ones.”

Participants will be able to follow the progress of their soil sample online, working with scientists to analyse the colour, shape and size of the bacteria living within it, and find out if any antibiotics are being produced.

Prof Bowater added: “Many of our most effective antibiotics have been found by scientists screening soil samples. It makes sense to keep looking there and getting samples from members of the public will help us on our way.”

Members of the public will be able to meet members of the Antibiotics Unearthed team, and can find out what antibiotics are, where they come from, and why we need them.

Prof Neil Gow, President of the Microbiology Society, said: “People taking part in Antibiotics Unearthed can make a difference in the search for new antibiotics and contribute to the awareness that these wonder drugs are a precious and finite resource needed to tackle life threatening infections.”

JIC spin-off Leaf Systems opened by Science Minister Jo Johnson

Leaf Systems International Ltd, a spin out company built on the world-leading UK bioscience research that takes place at the John Innes Centre, was today officially opened by Jo Johnson, Minister of State for Universities, Science, Research and Innovation.

The science behind Leaf Systems was developed, with BBSRC investment, at the John Innes Centre and its creators, Professor George Lomonossoff and Dr Frank Sainsbury, won the BBSRC Innovator of the Year award in 2012.

Leaf Systems use a novel efficient, safe and simple system – Hypertrans® – to quickly produce proteins in plants such as vaccines, antibodies or enzymes. The proteins can then be extracted through crushing the leaves and purifying the product.

The speed of the system means that it can rapidly produce large amounts of protein and so it is well suited to rapidly responding to emergencies like pandemics. Other potential uses include producing many proteins at the same time and so creating new biochemical pathways for producing complex ‘bioactive’ molecules such as novel anti-cancer drugs and anti-infectives.

Leaf Systems building

Leaf Systems building at night

Leaf Systems is part of the Norwich Research Park and joins a thriving research and innovation campus centred on world leading research institutes. It will provide services to companies and research organisations by producing sufficient quantities of these valuable proteins and other natural products to enable research and product development.

Universities and Science Minister Jo Johnson said: “UK science and research is world-leading and has played a key role in some of the most revolutionary discoveries of our time. Science will be at the core of the Industrial Strategy, maximising its potential to support local growth and drive investment through commercial partnerships.

“This pioneering technology is an example of British ingenuity – using plants to produce flu vaccines will benefit millions of people across the country.”

Professor Lomonossoff said, “The opening of the Leaf Systems facility represents the culmination of many years of research by myself and colleagues into fundamental virology. There is something rather magical about seeing these efforts being translated into the formation of a company, the construction of a building and the potential for great impact”.

Professor Dale Sanders, Director of the John Innes Centre said, “The John Innes Centre attaches priority to the commercial valorisation of our science. Leaf Systems is an excellent example of that prioritisation, highlighting as it does the enormous potential of plant science for both public good and economic growth”.

Chief Executive of BBSRC, Professor Melanie Welham said, “Leaf Systems is the result of long-term strategic investment in UK research and shows the strength of our bioscience community to not only produce ground breaking science but also to harness that knowledge to create new companies, products and services and foster economic growth”

Norwich scientists win international award in bid to solve antibiotic resistance

Norwich Research Park scientists have won a prestigious international award for a breakthrough that could help the fight against antibiotic resistance.

Prof David Russell from University of East Anglia’s School of Chemistry, in collaboration with Prof Rob Field from the John Innes Centre, were recognised for their method of performing a rapid diagnostic test to quickly identify bacterial pathogens.

At an award ceremony held at the Royal Society in London last night (21 Nov), the team was presented with a prestigious Longitude Prize Discovery Award which supports the development of a diagnostic device for anti-microbial resistance (AMR), one of the biggest challenges facing modern medicine.

Based on dipping a tiny sample into a solution of sugar labelled with gold, the system provides a quick diagnosis, with results being indicated by a rapid colour change. The simple ‘dipstick ‘ test is much faster than existing methods of testing, removing the need to send samples on for laboratory testing and allowing much faster decisions to be made about appropriate antibiotic treatment.

Russell and Field started the company Iceni diagnostics, a joint spin-out from the John Innes Centre and the UEA based at the Norwich Research Park’s Innovation Centre, in 2014 in order to explore the potential of this new technology. They received seed funding from Iceni Seedcorn Fund at end of September.

They are one of 12 winning teams who will use the prize to develop their technology and compete for the coveted Longitude Prize, a challenge with a £10 million prize fund to reward a point of care diagnostic test that most fully addresses the global problem of bacterial antibiotic resistance.

david-russel-and-rob-field

Prof Russell said: “We are delighted to be awarded this prestigious, highly competitive award. This discovery award has given us further motivation that we are working on an important international medical problem and heading in the right direction to try and solve the problem of bacterial resistance to antibiotics.”

Professor Rob Field said: “It is great to receive recognition for our efforts to take basic science through to potential products for medicine and agriculture. The JIC-UEA team have been working on these topics for more than ten years, but it is with the establishment of our joint spin-out Iceni Diagnostics that we began to achieve the necessary momentum to translate academic discovery into end-user devices”

Professor Dale Sanders, Director of the John Innes Centre said:

“This award recognises the great potential of Professor Field and Professor Russell’s research. Once developed the diagnostic could dramatically reduce unnecessary use of antibiotics, helping to address the global threat of drug-resistant infections which are killing up to 50,000 people every year in Europe and the US alone. We are proud to host Professor Field’s laboratory at the John Innes Centre and congratulate him and the Iceni Diagnostics team on winning this award.”

UEA vice-chancellor Professor David Richardson said: “Winning a Longitude Prize Discovery Award is a significant and prestigious achievement for Professors Rob Field and David Russell and all the team at Iceni Diagnostics.  This is a young spin-out company from UEA and the John Innes Centre undertaking vital applied research to help healthcare professionals diagnose whether an infection is caused by bacteria or viruses within just 15 minutes. The benefits of this research are considerable and range from human health to agriculture.”

For more information about Iceni Diagnostics visit: http://www.icenidiagnostics.com/

This item from UEA and JIC news pages.


Earlham institute
Quadram Institute Bioscience
John Innes Centre
The Sainsbury Laboratory
NHS NNUH
University of East Anglia

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