Cambridge, Swedish and US scientists have created the first cell atlas of mosquito immune cells to understand how the insects fight malaria and other infections. 

Researchers from the Wellcome Sanger Institute in Cambridge UK, Umeå University, Sweden and the National Institutes of Health (NIH), USA, discovered new types of mosquito immune cells, including a rare cell type that could be involved in limiting malaria infection.

They also identified molecular pathways implicated in controlling the malaria parasite.

Published today in Science, the new ‘gnatlas’ findings offer opportunities for uncovering novel ways to prevent mosquitoes from spreading the malaria parasite to humans and break the chain of malaria transmission. 

The atlas will also be a valuable resource for researchers trying to understand and control other mosquito-borne diseases such as Dengue or Zika.

Malaria is a life-threatening disease that affects more than 200 million people worldwide and caused an estimated 405,000 deaths in 2018 alone, the majority of which were children under five. 

It is caused by Plasmodium parasites, spread via the bites of female Anopheles mosquitoes. Breaking the chain of transmission from human to mosquito to human is key for reducing the burden of malaria.

The mosquito immune system controls how the insect can tolerate or transmit parasites or viruses, however little is known about the exact cell types involved. 

In this first in-depth study of mosquito immune cells, a team of researchers studied two types of mosquito: Anopheles gambiae, which transmits malaria, and Aedes aegypti, which carries the viruses that causes Dengue, Chikungunya and Zika infections.

Using cutting edge single cell techniques the researchers analysed more than 8,500 individual immune cells to see exactly which genes were switched on in each cell and identify specific molecular markers for each unique cell type. 

The team discovered there were at least twice as many types of immune cell than had previously been seen, and used the markers to find and quantify these cells in circulation, or on the gut and other parts of the mosquito. They were then able to follow how Anopheles mosquitoes and their immune cells reacted to infection with the Plasmodium parasite.

Dr Gianmarco Raddi, a first author on the paper from the Wellcome Sanger Institute, said: “We have carried out the first ever large scale survey of the mosquito immune system, and using single cell sequencing technology we found immune cell types and cell states that had never been seen before. 

“We also looked at mosquitoes that were infected with the Plasmodium parasite and for the first time were able to study their immune response in molecular detail, and identify which cells and pathways were involved.”

A previous study from the NIH team had shown that a process called ‘immune priming’ could limit the ability of mosquitoes to transmit malaria, by activating the mosquito immune system to successfully fight the parasite. 

In this study, the researchers discovered that one of the newly discovered immune cell types had high levels of a key molecule needed for immune priming, and could be involved in that process.

Dr Oliver Billker, joint senior author on the paper previously from the Wellcome Sanger Institute and now based at Molecular Infection Medicine Sweden, Umeå University, said: “We discovered a rare but important new cell type we called a Megacyte, which could be involved in immune priming, and which appears to switch on further immune responses to the Plasmodium parasite.

“This is the first time a specific mosquito cell type has been implicated in regulating the control of malaria infection, and is a really exciting discovery. We now need to carry out further studies to validate this and better understand these cells and their role.”

The researchers showed that specific types of immune cell – granulocytes – increased in number in response to infection, and revealed that some of these could develop into other immune cells. 

They also discovered that immune cells in the mosquito’s gut and other tissues are actively recruited into the circulation to fight infections after lying dormant on the mosquito fat body.

Dr Sarah Teichmann, an author from the Wellcome Sanger Institute, said: “The team has created the first mosquito immune cell atlas, to shed light on how mosquito immune systems fight infections. Mosquitos appear to have a sweet spot of immunity to parasites like malaria, with enough immunity to the infection that it doesn’t kill the mosquito but not enough to remove the parasite. 

“This atlas offers a vital resource for further research, which could reveal ways to modify the mosquito immune response to break the chain of disease transmission.”

• PHOTOGRAPH: Dr Sarah Teichmann, Wellcome Sanger Institute. Credit – Sebastian Nevols.

3D printing has enjoyed a lot of airtime during the coronavirus crisis. It is also rapidly developing, writes Alasdair Poore, head of Intellectual Property at law firm Mills & Reeve’s Cambridge office. 

These features make Intellectual Property highly relevant, both as a business opportunity and a potential risk.

While not a new phenomenon, 3D printing (or additive manufacturing) is increasingly being utilised as a key manufacturing tool and has been adopted into the manufacturing processes of a number of industries, most notably the automotive sector. 

Examples of its use stretch from parts for F1 racing cars and aeroplanes through to use in medicine and dentistry to consumer items including jewellery. 

Perhaps more engagingly, it has reached the wider public with toys and make-it kits for children and adults. 

During the coronavirus pandemic there has been an exceptional demand for PPE and 3D printing has stepped up to the mark. It has demonstrated its versatility in the face of an unprecedented crisis, being used to make parts for ventilators, face masks and other products. 

It has been used by major manufacturing companies and research organisations, and by individuals in private households.

3D printing is a broad term covering a very wide range of processes which have a common element – the addition of material in steps to build up an object with the desired overall shape (and structure).

There are many ways of achieving this. And it can be used at scales from microscopic to the size of buildings or bridges, as well as ordinary ‘human’ scale.

All of these approaches, however, have some common elements: they are versatile, can be prototyped quickly and lend themselves to product development – and that rapid product development lends itself to obtaining useful IP protection; the more so because where 3D printing provides real opportunities for the innovator, the same features facilitate copying the innovator. Hence the need to consider  IP protection at every stage of the 3D printing process.

Moreover, the technologies used in 3D printing are still, relatively, in their infancy. There are many opportunities to develop the technology further, and this provides a separate stream of potential innovation – in the processes themselves, in material used in those processes, and in the pre- and post-processing for the materials and products produced. 

As an illustration, over the 10 years to 2017 patent filings for additive manufacturing technology look to have grown exponentially. 3D printing technology is custom-made for IP opportunities. Here are a few reasons why:-

• Fast prototyping enables a rapid development, testing and enhancement cycle and an opportunity to solve both known problems and ones you did not know you had when you started
• The output itself – a 3 dimensional article – has features of shape and appearance: these provide a basis for protection as designs, even, in some cases if there is a substantial functional requirement
• There is plenty of knowhow to be accumulated in designing a product for optimal production on an additive technology platform. Understanding how to layer the product, what is strong, weak, what is fracture prone. Other technologies such as injection moulding have become part of the engineering skill set – for 3D printing there is still a learning curve.

There are new ways of designing which would not have been possible in other technologies – or are very expensive.

Each of these give rise to potential for IP protection – for example, patents on innovative solutions in 3D printing processes including for new and powerful 3D printing tools; through to intellectual property rights which specifically address the shape or appearance of the articles created through a 3D printing process, such as rights in designs (and copyright in drawings and their electronic equivalent); to trade secrets, confidential information, know-how, and very difficult to protect experience and staff skills.

The key to getting the best out of the opportunity is to have (or to develop and implement) an intellectual property strategy. That is not just to protect anything that moves or run scared from any IP sighted in the distance – but to understand why, when, and how opportunities and risks in relation to intellectual property arise and can be managed in a commercial and proportionate way.

That and the core elements and impact of each of these intellectual property rights, their ownership (for example where third parties such as contractors are involved), and some of the challenges are for a future article.
In the meantime, here is a quick (and not very legal) summary of the most important technical intellectual property rights.

Patents protect inventions of a technical character – that is new products or processes which are inventive – not obvious to the engineer in the relevant field.

The invention must be ‘claimed’ in an application to national or regional patent offices. The application must usually be made before the invention is disclosed.

They are relatively costly to apply for and maintain, and there needs to be a reasonable proportionate commercial justification for seeking patent protection.  Professional advice is essential.

Design rights broadly protect the shape or appearance of an article. They can arise automatically (in which case they protect against copying); or registered (with national IP offices) in which case, if the design was a new one, making the same or similar design, whether or not it is copied, may infringe.

The requirements differ considerably between countries – for example, whether the design is purely functional, whether it is visible in use, and whether the shape is constrained by other factors may matter; and some countries, like the UK, have several different forms of design protection.  

Generally professional advice is desirable for registering a design, and may be helpful for optimising protection from unregistered designs or copyright in design works.

Confidential information is best protected either by keeping the information secret or by using written (confidentiality) agreements – and marking it appropriately.

The level of protection possible will depend on the type of information.  Information or know-how which forms part of the skills and expertise of employees will always be more difficult to protect – and if protection would be worth having, deserves specific attention.

Those can form the substrate for a simple two sentence strategy: Do assess what intellectual property rights you have, make it clear to others that you have rights, and watch what others are doing – with your innovations or what you might find useful; and consider expressly protecting your rights, policing them and enforcing them when appropriate. 

A stitch in time saves nine – even in the age of 3D printing.

mills-reeve.com

https://www.mills-reeve.com/

SciBite, a semantic AI company headquartered in Cambridge UK, has been acquired for an undisclosed sum by global research publishing and information analytics provider Elsevier.

A recent Queen’s Award winner, SciBite is based in the Wellcome Trust Sanger Institute Morgan Building and provides an enterprise-ready semantic software infrastructure to standardise and transform scientific information silos into clean, interoperable data. 

Globally influential, the technology business supports the top 20 pharma companies with use cases across life sciences.

Elsevier, part of UK power player RELX, has acquired the Cambridge innovator to help customers make faster, more effective R & D decisions through advanced text and data intelligence solutions.

SciBite’s solutions identify and extract scientific insights from both structured and unstructured text and content, to identify key concepts such as drugs, proteins, companies, targets, and outcomes. 

This semantically-enriched, machine-readable data, helps SciBite’s customers around the world make streamlined, more efficient decisions. SciBite was founded in 2011 by Dr Lee Harland, who currently serves as chief scientific officer. 

SciBite’s major products include: TERMite, an AI and ontology driven text analysis engine; DOCstore, which transforms search through semantic indexing; and CENtree, a next-generation collaborative ontology management platform; they are complemented by a suite of apps that support its core technology and allow customers to automate data-curation and manage terminology standards.

Dr Harland said: “I am incredibly proud of everyone at SciBite; we believe that our continued investment in innovative technology enables our customers to address the huge challenges they face in creating, connecting and analysing disparate content and data. 

“Our track record in driving new insights and efficiencies within drug discovery and the wider life sciences is something we will continue to build upon in this next phase of our journey.”

Rob Greenwood, CEO and President of SciBite, added: “This is an exciting next step for our business. The combined offering of Elsevier’s high-quality content and data and the innovative technology from SciBite will deliver amazing value for any data led strategy across the scientific community. 

“As part of the Elsevier organisation, SciBite will have the ability to deliver enterprise technology, and new advances in scientific insight and discovery across its broad reaching global customer base.”

Elsevier helps researchers and healthcare professionals advance science and improve health outcomes for the benefit of society. To support this, Elsevier’s Life Sciences Solutions division is transforming from a provider of reference solutions into a creator of data and information analytics capable of supporting multiple scientific domain-specific use cases, ranging from search and discovery through to machine learning and AI.

SciBite’s proven and award-winning solutions will enable Elsevier to develop its Life Sciences Solutions services, such as: Reaxys, which powers chemistry research and development; Embase, the world’s most comprehensive international database of biomedical information; and Entellect, its FAIR data compliant platform that integrates, stores, and enriches client data with Elsevier and third-party content into a common analytical environment.

Cameron Ross, managing director Life Sciences Solutions at Elsevier, said: “The life sciences and corporate R & D communities face complex challenges, with an ever-expanding sea of data and content to extract knowledge from.

“We aim to combine Elsevier’s expertise and content from existing products, with SciBite’s impressive capabilities and suite of ontology-led products, to support more customers around the world make data led decisions in the drug development process.”

Leading life science and technology law firm Taylor Wessing advised on the acquisition; its team included Ross McNaughton, Adrian Toutoungi and Charlie Adams – all based in Cambridge.

Cambridge University spin-out Sorex Sensors has raised £900,000 to fund further development of its novel sensor technology and target a global market tipped to be worth $323 billion inside four years.

The business has also made key changes of the very pinnacle of management to steer the bid for global dominance.

Investors in the latest round include the university’s commercialisation arm Cambridge Enterprise, which matched funds raised by a set of Cambridge- and London-based investors including the Cambridge Angels, SyndicateRoom and Camvision.

In a parallel move, Sorex reveals that co-founder and former chief technology officer Dr Mario de Miguel Ramos has been appointed CEO – replacing Michael LeGoff, who has taken on the role of executive chairman. Professor Andrew Flewitt, head of electrical engineering at the University of Cambridge and also a co-founder of Sorex, has transitioned from chairman  to chief scientific officer.

The global market for sensors – valued at $153.3 billion in 2018 – is expected to increase to $323.3 billion by 2024. Sorex launched its first product based on its breakthrough film bulk acoustic resonator (FBAR) sensor technology last year. 

It consists of a particulate sensor along with an accompanying development kit – and is designed for use in devices for monitoring indoor air quality.

Professor Flewitt said: “The team has done a fantastic job so far and Mario will continue to work closely with Michael as we ramp up production and bring new products to market. 

“Our next step will be to release an array of sensors and we are on track with that. We are currently working on ‘functionalising’ the sensors to detect specific gases and plan to have a proof of concept ready later this year.”

The company’s initial focus is on improving the monitoring of indoor air quality. Poor indoor air quality has been linked to a range of illnesses – particularly lung diseases like asthma and chronic obstructive pulmonary disease. 

Indoor air can be affected by many factors, including chemicals used to clean or decorate, fuels used for heating and cooking, building and furnishing materials, and tobacco smoke. This can lead to harmful levels of substances like carbon monoxide and volatile organic compounds such as formaldehyde.

The FBAR sensor developed by Sorex is extremely small, measuring less than 0.5 square millimetres. It uses microwatts for power and can detect changes in mass down to femtograms – the weight of a single virus. That makes it the most accurate and cost-effective sensor available.

Dr de Miguel Ramos said: “I am delighted to be leading our world-class team as we embark on this exciting new stage of our journey. Our initial focus is the monitoring of air quality – with our sensors acting as your eyes, ears and nose to detect any dangerous build-up of compounds before they reach harmful levels. But our innovative sensor technology has the potential to transform a whole range of industries.”

Elaine Loukes, an investment director in the seed funds team at Cambridge Enterprise, said she was delighted at the progress the team had made over the past two years. 

She said: “Improving indoor air quality is recognised as a matter of urgent importance and I believe the Sorex technology will offer a step change in the ability to detect and measure harmful compounds, leading to healthier environments at home and in the workplace.”

• Sorex Sensors manufactures high-sensitivity MEMS mass sensors to transform industrial and consumer products. The University of Cambridge spin-out is based in the Maxwell Centre at the university’s West Cambridge site. It also has research teams at the Technical University of Madrid and the University of Warwick in the UK. 

Successive governments have recognised business funding reliefs as a valuable means of encouraging investment into technology companies, writes James Francis, partner at Ensors Chartered Accountants. 

The UK provides three such tax-advantaged schemes; the Enterprise Investment Scheme (EIS), the Seed Enterprise Investment Scheme (SEIS) and the Venture Capital Trusts (VCT) regime. 

EIS enables individuals to invest in small and medium-sized companies in return for generous tax reliefs, while SEIS provides relief for smaller investments.  

EIS’s headline incentives are the ability to invest up to £1 million (per tax year) in shares issued by a qualifying company in return for a 30 per cent non-repayable Income Tax credit and a potential exemption from Capital Gains Tax (CGT) when the shares are sold; in both cases the EIS shares must be held for at least three years. 

There is further Income Tax relief for investment losses if the company fails. It is also possible for investors to defer CGT on the disposals of other assets by reinvesting proceeds into qualifying EIS shares.

While changes introduced from 2015 have limited the scope of EIS for many investments, more recent changes have made EIS more generous for knowledge-intensive companies in terms of how much a qualifying company can raise, the period over which it can first raise EIS investment and how much the individual can invest. 

This applies to companies that carry out a high level of innovation creating IP they intend to exploit or where at least 20 per cent of the workforce is “skilled”.

SEIS is specifically aimed at smaller companies which have only recently begun to carry on a qualifying trade.

SEIS investors can claim Income Tax relief equal to 50 per cent of their subscription for qualifying shares of up to £100,000. Gains from selling qualifying SEIS shares are exempt from CGT provided the investor has held the shares for three years. 

CGT reinvestment relief also exists so that where an individual realises a capital gain and reinvests all the proceeds in SEIS shares, half of the gain will be tax exempt.  

If the shares are sold within three years of issue, all SEIS reliefs are clawed back. A company cannot issue SEIS qualifying shares if it has already issued EIS shares or received investment from a VCT.

EIS and SEIS shares will normally qualify for Inheritance Tax business property relief after two years’ ownership.

A VCT is an investment company with shares listed on a European regulated market. It is required to invest in and maintain a portfolio of qualifying trading companies with a permanent establishment in the UK. 

The investment differs from EIS/SEIS in that the investor buys into the investment vehicle as opposed to the investee company. VCT is therefore a more passive investment, albeit one that dilutes the risk of investment in specific companies.

The investor can claim income Tax relief at 30 per cent on the investment made into the VCT, limited to a maximum investment of £200,000 per tax year. 

This relief is clawed back if the VCT shares are sold within five years of the date of issue. Dividends paid by the VCT on qualifying investments are not taxable and gains made on the disposal of VCT shares are exempt from CGT, with no minimum holding period. The flipside is that losses incurred on a sale of VCT shares are never allowable for capital gains tax purposes.

A sunset clause for EIS and VCT (but not SEIS) income tax relief has been introduced. This ensures that income tax relief will no longer be given to subscriptions made on or after 6 April 2025, unless the legislation is renewed by Treasury Order.

Please be aware this is a very high-level summary of EIS, SEIS and VCT; all are subject to various complex requirements. Professional advice both at the time of investment and going forward is essential to ensure that reliefs are obtained and not subsequently clawed back.

ensors.co.uk

The global pull of the Cambridge life science cluster has prompted a UK startup growing meat products from animal cells to move its HQ here from Bristol as it chases a slice of a $1.4 trillion meat market.

Two-year-old Higher Steaks is moving into the Cambridge Science Park’s new Incubator building and is already seeking to recruit stem cell scientists, tissue engineers and bioprocess engineers. 

The company is also currently closing a seed round which CEO Benjamina Bollag says will get the business ready to pilot plant and secure necessary regulatory applications. 

While in global terms a handful of US companies have a head start, Higher Steaks believes it has a market lead for a UK company in the precise segment in which it is operating.

Dr Ruth Faram, head of Research & Development, is moving to the new Cambridge HQ which chief scientific officer Dr James Clark – formerly of PredictImmune – is pathfinding.

Bollag told Business Weekly that Higher Steaks planned to leverage a number of unique selling points in a world becoming increasingly vegan and keen to seek healthier meat products or alternatives. She says the meat the company can produce from animals’ cells is better for agriculture, animal welfare and human healthcare.

Its meat doesn’t contain antibiotics, is sustainable and does not require animal slaughter. Healthcare benefits are said to be numerous and its solution eliminates potential killers such as salmonella which causes around 420,000 deaths a year.

Using state-of-the-art cell culture techniques, Higher Steaks professionals extract a small sample of cells from an animal. They then expand those cells by feeding them a rich and animal-free growth medium. 

When these cells have grown, they guide them to become muscle, fat and other types of tissue in order to form the desired meat product. 

Early successes have produced the world’s first prototypes of laboratory-grown bacon rashers and pork belly. 

Bollag says the pork belly is approximately 50 per cent cultivated meat to 50 per cent plant-based and the bacon around 70 per cent cultivated meat to 30 per cent plant-based.

“The production of the first-ever cultivated bacon and pork belly is proof that new techniques can help meet the overwhelming demand for pork products globally,” she said.

“Our mission is to provide meat that is healthy and sustainable without the consumer making any sacrifices on taste: The prototype products represent a major milestone for Higher Steaks.

“We have made substantial advancements in a relatively short amount of time whilst managing cash flow. We are accelerating the development of cultured pork products and the company is now focused on the next steps to bring our products to everyone’s homes.”

One of the biggest challenges ahead is creating product at prices affordable to consumers and trade customers. 

Bollag believes that increased global awareness of the risks of pork production will help the company’s commercial viability long-term but stresses that getting the product right is more important to build a sustainable company with sought-after products than rushing to try to be first to market.

“These are early days and our intention is to build a business and products that stand the test of time. That means getting the regulatory process rock solid and building a great team and solid financial foundations as we progress to every new stage of production. We believe the biotechnology cluster as it has evolved in Cambridge will be a tremendous asset for Higher Steaks as we continue to grow our team and technology. We are aware of the risks but also the massive potential in our marketplace.”

The management team is highly experienced. Before founding Higher Steaks, Bollag – a Swiss national – co-founded a London-based B2B electronics company selling to FTSE500 companies. 

She has also worked at Israeli 3D printing company, Stratasys, at the digital marketing division of PepsiCo’s joint venture with Strauss and was the lead developer an EdTech startup. She holds a Master of Chemical Engineering from the Imperial College London.

Dr Faram has over 15 years of experience working with stem cells and post doctoral expertise in induced pluripotent stem cells and epigenetics.

Dr Clark was chief technology officer of PredictImmune and has led the development of biotech and pharma products at early-stage and publicly traded companies.

The company’s decision to move to Cambridge has been hailed as potentially transformative for the company and the sector by Tony Jones, CEO at the influential life sciences member organisation One Nucleus. 

He told Business Weekly: “In bringing this cutting edge biomedical technology to the region Higher Steaks not only gives the platform the best possible chances of success but also adds significant potential to the Cambridge cluster to be leaders in the rapidly emerging field of laboratory grown meat and the future of sustainable agriculture.”

Quoted Cambridge company Marshall Motor Holdings is using its UK market leading position and substantial war chest to identify potential fresh acquisitions and swoop when the time is ripe.

CEO Daksh Gupta told Business Weekly the company has £150 million of liquidity, remains highly cash generative despite the backdrop of the coronavirus pandemic and believes it is well placed to add to its portfolio of prime dealerships.

The cash runway remains highly visible and prosperous through to 2023, staff are steadily returning from the virus lockdown and both demand and waiting lists are running hot.

When the company posted its unaudited interim results for the six months to June 30 on Tuesday the share price rose 3.20 per cent despite the lack of a dividend. 

Also, the London Stock Exchange chat wire where shareholders are never frightened to hold back, was unanimously positive about medium and long-term prospects for the business.

Gupta said that with the group’s excellent brand partner relationships, strong balance sheet, recently renewed £120m revolving credit facility, depth of management team and highly engaged colleagues, MMH believed it was well placed to capitalise on value accretive growth opportunities.

“Acquisitions have got to  be right, not just strategically but they also have to make financial sense,” Gupta said. “Since I arrived we have bought and sold 161 businesses so we are getting the hang of it now. 

“The really encouraging factor from the latest results is that we continue to trade ahead of the market – we have been so time and time again – and we are sufficiently confident to state that we will turn the reported loss reported today into break-even.

“With so many car producers’ factories closed from the March lockdown, we have continued to use technology to show people used and new cars online and we have built substantial pent-up demand. We have continued to provide unparalleled customer support.”

For the record, H1 revenue was down to £859.3m from £1.183 billion in the first half of 2019 – purely because of COVID-19. The 2019 H1 profit of £14.8m turned to a £10.7m loss this time. The company’s net assets were barely eroded.

Gupta reports highly encouraging sales since June 1 and expects these to continue. “Despite the significant challenges presented by COVID-19, the group has delivered a resilient first half performance and once again outperformed the market.

“Since full reopening under COVID-19 secure guidelines on June 1, trading has been robust and our important Q3 order take is encouraging.

“The impact of COVID-19 will accelerate the rationalisation and consolidation of the UK franchise dealer network. 

“With the group’s excellent brand partner relationships, strong balance sheet, recently renewed £120m revolving credit facility, depth of management team and highly engaged colleagues, the group believes it is well placed to capitalise on value accretive growth opportunities and is therefore well placed to deliver long-term shareholder value.”