BioScience Today 28

SCIENCETODAY

BIO

THE BIG INTERVIEW • WORK IN BIOTECH • FUTURE OF GENOMICS • COVID IMMUNITY • NANOCHANNELS

ISSUE28

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www.biosciencetoday.co.uk

| foreword |

foreword Karen Southern

Significant R&D changes could threaten growth of life sciences sector

Editor in chief

The UK’s life sciences are thriving, as evidenced in this latest issue.

Editor Karen Southern karen.southern@distinctivegroup.co.uk

Design Distinctive Media Group Ltd, 3rd Floor, Tru Knit House, 9-11 Carliol Square, Newcastle, NE1 6UF Tel: 0191 580 5990 distinctivegroup.co.uk

Advertising Distinctive Media Group Ltd, 3rd Floor, Tru Knit House, 9-11 Carliol Square, Newcastle, NE1 6UF Tel: 0191 580 5477 e: liz.hughes@distinctivegroup.co.uk distinctivegroup.co.uk

However, I thought I would draw attention to a couple of issues which could have far-reaching implications for our much-lauded R&D sector.

The first is a warning from RSM UK about ‘significant’ changes to R&D tax relief. Their recent press release states: ‘Life science businesses need to act now to avoid missing out on research and development (R&D) tax reliefs.

The most significant changes to R&D tax relief since its introduction in 2000 are imminent and could impact the sector’s growth. Start-ups and fledgling businesses that rely on R&D activity overseas should review their tax position and business model now to prepare for the changes.

‘The life sciences sector views the R&D tax relief as a well-established, reliable tax incentive that encourages innovation. Start-ups often rely on the relief to support cashflow in the early stages of their lifecycle. However, over the past year, the government has expressed increasing concerns over the regime’s susceptibility to abuse, prompting a rethink.

‘A further driver behind the changes is to encourage businesses to ‘buy British’ and invest in UK businesses. The government has proposed that from April 2023, R&D relief is withdrawn for expenditure incurred overseas, including subcontracted R&D and payments to overseas workers, with some limited exemptions.’ Find out more here.

Distinctive Media Group Ltd or BioScience Today cannot be held responsible for any inaccuracies that may occur, individual products or services advertised or late entries. No part of this publication may be reproduced or scanned without prior written permission of the publishers and BioScience Today.

Another potential spanner in the works, as highlighted by Arnold & Porter (London) is the

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new National Security and Investment Act. Their lawyers have spent months assessing its first months in operation, and say the Act’s ‘burden’ could actually discourage investors in our life sciences.

The team advises that 20% of investments subject to mandatory reporting under the new Act related to Artificial Intelligence investments, heavily used via health-tech in the life sciences sector; for example, in monitoring subjects in clinical trials to capture data. The law firm says that the regime is likely to cause increased burden, costs, uncertainty and timing for deals in life sciences.

A spokesman pointed out that: “Companies in the life sciences sector are often small start-ups with potentially very valuable pipelines and need quick access to cash to carry forward expensive R&D projects - often raised on multiple rounds.

The potential need for multiple filings at each stage, as well as in general the review and assessment process under the NSIA might delay how quickly they can be funded, or discourage investors all together.”

Arnold & Porter adds that the first few months of the regime has also illustrated a lack of transparency in the Department of Business, Energy and Industrial Strategy (BEIS) in its decision making in giving clearance to deals makes it harder for investors and businesses to understand the reasoning for a decision on a particular transaction and make representations as to why national security concerns would not arise in that specific case. Read more here.

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| contents |

features

Going against the grain

10 8 Overcoming the challenges of working with genetically edited cellsand related diseases

Protecting the confidentiality of individuals vs. the desire to improve healthcare through data

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| contents |

contents / www.biosciencetoday.co.uk / issue 28 /

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Foreword

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Contents

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the big interview Aberdeen-based Elasmogen recently secured £8 million investment for its soloMERTM platform, led by BGF and Scottish National Investment Bank with additional support from existing investor Scottish Enterprise. This will enable the company to continue developing its pipeline of next-generation drugs through pre-clinical trials.

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WORK IN BIOTECH Singular Talent speaks to over 1,500 candidates every year and MD Tom Froggatt has seen the pandemic change what bioscientists want most from employers.

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FUTURE OF GENOMICS Precision breeding for a sustainable future: unpacking the future of genomics. Neil Ward, General Manager of PacBio EMEA, examines the potential impact of the UK’s Precision Breeding Bill.

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COVID IMMUNITY Your immune system’s ability to combat COVID-19, like any infection, largely depends on its ability to replicate the immune cells effective at destroying the SARS-CoV-2 virus that causes the disease.

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NANOCHANNELS The development of new drugs and vaccines requires detailed knowledge about nature’s smallest biological building blocks – biomolecules. Swedish researchers have devised a new microscopy technique that allows proteins, DNA and other tiny biological particles to be studied in their natural state in a unique way.

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32 Over 1,000 genes linked to severe COVID-19

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GLOBAL SURVEILLANCE MODEL Broad viral surveillance is essential in pandemic prevention to allow for detection of potential threats and the immediate early launch of health protocols against pathogens. Yves Dubaquie, senior vice president of diagnostics, PerkinElmer, Inc., investigates how this could work.

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MATERNAL MICROBIOME Researchers studying mice have found the first evidence of how a mother’s gut microbes, the maternal microbiome, can help in the development of the placenta, and the healthy growth of the baby.

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| industry contributors |

Caroline is CEO and founder of Elasmogen, a company that discovers and develops soloMER biologics for the treatment of inflammatory diseases and cancer. Before establishing Elasmogen, she successfully led teams at Wyeth and subsequently Pfizer in Global Bio-therapeutic Technologies progressing early platform technologies to late-stage clinical development.

Neil Ward General Manager of Pacific Biosciences (EMEA) Neil’s focus is on expanding and developing the PacBio EMEA team and infrastructure to capitalise on the immense potential for genomics in this area of the world. Neil is a genomics industry veteran with more than two decades of global experience. He most recently served as Senior Sales Director for Northern Europe at Illumina. In his various commercial roles, Neil has served as a key contributor in many of the world’s largest genomics projects including Genomics England’s 100,000 Genome Project, the Estonian Genome Project, and the whole genome sequencing of the 500,000 UK Biobank samples. Prior to his 13 years at Illumina, Neil held bioinformatics and sales roles at leading institutions, including Agilent, Silicon Genetics, Oxford Biomedica and Celltech.

Wendy Lloyd-Goodwin Founder, Life Science Law Wendy Lloyd-Goodwin is Founder of Life Science Law, a disruptive new company providing leading legal and compliance advice for businesses on pharmaceuticals, consumer wellbeing products, medical devices and cannabinoids.

to advertise or contribute to the next edition advertising: liz.hughes@ distinctivegroup.co.uk editorial: karen.southern@ distinctivegroup.co.uk

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Dr Caroline Barelle CEO of Elasmogen

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| news |

Unravelling the mysteries around type-2 diabetes Researchers at University of Leeds have pinpointed a molecule mutation that plays a key role in the disease.

For more than 30 years, scientists have been trying to unravel the mystery of how a key biological molecule self assembles into a rogue protein-like substance known as amyloid, which is thought to play a role in the development of type-2 diabetes - a disease that affects 300 million people worldwide.

modulators, which can control the process: one of the compounds delays it, the other accelerates it.

These molecule modulators can be used as “chemical tools” to help scientists investigate the way amyloid fibrils grow and how and why they become toxic.

Significantly they also offer “starting points” for the development of drugs that could halt or control amyloid fibril formation and help in the urgent search to find ways to treat type 2 diabetes.

A team of scientists at the University of Leeds has, for the first time, been able to identify the step-by-step changes that take place in the molecule known as human islet amyloid polypeptide, or hIAP, as it changes into amyloid.

Sheena Radford, Royal Society Research Professor and Professor of Biophysics at the Astbury Centre for Structural Molecular Biology at Leeds, who supervised the research, said: “This is an exciting and huge step forward in our quest to understand and treat amyloid disease and to tackle a major health issue that is growing at an alarming rate.

They have also discovered new compounds that are able to speed up or slow down the process.

In healthy people, hIAPP is secreted by islets in the pancreas alongside the hormone insulin and it helps to regulate blood glucose levels and the amount of food in the stomach. When hIAPP malfunctions, it forms clumps of a proteinlike substance called amyloid fibrils that kill the insulin-producing islets in the pancreas.

“The compounds we have discovered are a first and important step towards small molecule intervention in a disease that has foxed scientists for generations.”

The research team looked at hIAPP found commonly in the population and a rare variant found in people with a genetic mutation known as S20G which puts them at greater risk of developing type-2 diabetes.

The build-up of amyloid fibrils is seen in people with type-2 diabetes although the exact mechanism of how it triggers disease is not known.

AMYLOID FIBRIL FORMATION LINKED TO DISEASE

The research findings - Tuning the rate of aggregation of hIAPP into amyloid using small-molecule modulators of assembly – were published in the journal Nature Communications.

Understanding amyloid fibril formation is a key area of health research. The formation of fibrils is believed to be a factor in a range of life-limiting illnesses including Alzheimer’s Disease and Parkinson’s Disease, as well as type-2 diabetes.

The paper not only describes the complex molecular changes seen in hIAPP molecules as they transform into amyloid fibrils, the scientists also announce that they have discovered two compounds, described as molecule

Professor Radford added: “The results are also hugely exciting as they open the door to using the same type of approaches to understanding other amyloid diseases, the vast majority of which currently lack any treatments.”

“This is an exciting and huge step forward in our quest to understand and treat amyloid disease and to tackle a major health issue that is growing at an alarming rate. ” Sheena Radford, Royal Society Research Professor and Professor of Biophysics at the Astbury Centre for Structural Molecular Biology, Leeds

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| gene editing production |

Overcoming the challenges of working with genetically edited cells Sonia Jassi, Drug Discovery and Synthetic Biology Lead at Automata, examines how gene editing production could be scaled up for the benefit of UK labs.

The UK government is in discussion around a new bill which may allow genetically edited plants and animals to be grown for food in the UK. But is the bio synthetic industry prepared for this innovative science to be scaled for wider application?

Gene editing has huge potential to support the UK’s sustainability targets and encourage people to be more aware of the foods we eat. UK scientists have the power to help farmers and food producers to develop plants and animals with beneficial traits – like crops that are more resistant to diseases and require fewer pesticides.

With between 20 per cent and 40 per cent of all crops grown being lost to pests and diseases, this would be huge step forwards for the resilience of crop production, and could help the UK agriculture industry boost productivity.

If the bill is passed, there will be opportunities to go beyond looking at what we eat with genetically edited food and start to explore different materials for clothing for example. In fact, companies are already developing innovative solutions like synthetic clothing dyes and vegan leather made from mushrooms.

Scale is critical if these opportunities are to become a reality. But there are currently a number of challenges that the industry faces.

A LACK OF REGULATION The first challenge is around regulation, especially in cultured meat and plants. Currently the EU’s rules around gene editing focuses on legal interpretation rather than science – which has restricted the UK’s agricultural research institutions from carrying out research. This is because it can be a challenge for organisations to know if the right regulatory framework is in place for research and development (R&D) where easy growing and mass production of cells is required – especially when they need to be tested with humans.

If passed, this bill will provide the beginning of more structured regulatory framework that will support the

growth of precision bred plants and animals and potentially attract investment into agri-food innovation in the UK. However, there is still the challenge of being able to scale production to a level that will make these products widely available across the UK and allow us to reap the full benefits of gene editing.

SCALING PRODUCTION WITH AUTOMATION In order for the synthetic plants and meat industry to develop and grow, organisations need to be able to deliver products to market at scale. However, the environment that cells grow in requires very high levels of accuracy, with reproducibility and close control being critical parts of the process. This means enabling mass production is a challenge, as human error and contamination are both a risk when throughput needs to be increased.

This is where automation and robotics can play an important role. Scientists are talented, skilled individuals, but it can be impossible to manually keep up with both the pace and quality needed to scale development. With automation, it’s possible to run assays faster and for longer than scientists can, by using remote management to run assays through the night for example. This increases throughput and allows scientists to carry out R&D in other areas.

With automation, scientists can also be more confident in the accuracy of their results and draw conclusions faster.

Automated processes do the same thing, the same way with the same results, and developments to cell growth and editing can be made with certainty that all other variables are controlled.

Leading cell culture companies are looking to distribute novel products to market at pace, and automation can be a powerful tool to bring a product from R&D to mass production faster, giving companies a competitive edge.

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| gene editing production |

CULTURE CHANGE Another challenge to scaling genetically edited products is the culture change required to embrace automation. While automation is often used at the R&D stage of projects, applying it to more areas and using it to scale production may be new to many organisations and teams – and a mindset that embracing change and evolution in the lab space is critical.

One way to address this is with a focus on training for lab scientists, to help them understand the benefits of automating processes. It’s also important to start small, encourage uptake of new technology and then expand – rather than transforming an entire lab overnight. This is

where modular automation systems can be useful – as they can be scaled up – or down – where required in a lab, both to meet demand from scientists and to match the physical space and layout.

While this bill is still under debate, automation has an important role to play in the scaling of gene editing for any purposes – and will be critical for labs to have confidence in a flexible and agile production model while maintaining the control and accuracy required to grow cells. By focusing on automating workflows and removing the burden of repetitive tasks for scientists, UK labs could be well placed to drive forward a new era of synthetic biology innovation to market.

“Gene editing has huge potential to support the UK’s sustainability targets and encourage people to be more aware of the foods we eat.

UK scientists have the power to help farmers and food producers to develop plants and animals with beneficial traits – like crops that are more resistant to diseases and require fewer pesticides.”

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| health data |

Protecting the confidentiality of individuals vs. the desire to improve healthcare through data Wendy Lloyd-Goodwin, Founder of Life Science Law, looks at the implications of a new EU-wide framework for health data, including for research and clinical trials.

WAITING FO eu clinical tria

The EU is hoping to achieve a quantum leap forward in the way healthcare is provided to people across Europe. It wants to empower people to control and utilise their health data in their home country or in other Member States while also providing a framework to use health data for research, innovation, policy-making and regulatory activities.

The European Commission recently launched its European Health Data Space initiative aiming to give citizens access to their e-prescriptions and health records online. This system, to start by 2025, will be connected with all 27 EU member states, meaning people can travel around the EU and still access their health information. Researchers and pharma companies will also get access to anonymised data to improve the development of medicines, including making personalised cancer treatments or using artificial intelligence. Regulators and policymakers could also get access to improve health policy decisions.

“With the European Health Data Space, we can harness the power of health data and stronger health research, with citizens in control of their data at all times,” stated Health Commissioner Stella Kyriakides. “It will be a game changer for how we deliver healthcare and health solutions, always for the benefit of citizens and patients.”

The European Health Data Space is just one of many new initiatives designed to improve healthcare across Europe.

Another is the EU Clinical Trials Directive (EU-CTR) which was brought in to harmonise and simplify the processes for the application and supervision of clinical trials throughout

the European Union. The Regulation enables sponsors to submit one online application via the CTIS for approval to run a clinical trial in several European countries, making it more efficient to carry out such multinational trials.

The new Regulation will improve information-sharing and collective decision making on clinical trials and increase transparency of information as EU-CTR requires transparency throughout the development process.

Protocols, for example, are subject to EU-CTR’s public disclosure rules. Sponsors will need to consider their options for deferring publication of specific details, including the study protocol, and the onus is on them to protect patient confidentiality at the point of submission.

The new transparency rules intend to promote greater public awareness and understanding of clinical trials.

HEALTH DATA AND DATA PRIVACY LAWS While it is clear to see that health data sharing is a major priority for the EU Commission and to remove obstacles to the smooth functions of the data economy, it does prove challenging when it comes to patient confidentiality.

There is potential conflict between the confidentiality of individuals and their healthcare versus the desire to share data widely to support improvements in healthcare.

Under current data privacy laws, consent is required for any personal data to be shared at all. Yet a recent Assessment of the EU Member States’ rules on health data, in light of GDPR, found that a number of legal and operational issues

“There is potential conflict between the confidentiality of individuals and their healthcare versus the desire to share data widely.”

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| health data |

wendy lloyd-goodwin, founder, life science law Wendy Lloyd-Goodwin is Founder of Life Science Law, a disruptive new company providing leading legal and compliance advice for businesses on pharmaceuticals, consumer wellbeing products, medical devices and cannabinoids.

OR FEATURE: als regulations need to be addressed to ensure that European healthcare systems can make best possible use of health data. The evidence gathered through the study showed that there is a strong interest in the prospect of a European Health Data Space, but that it would require a sound level of legal and operational governance. The need for operational governance embracing the FAIR data principles1 was highlighted, which in turn emphasised the need for widespread implementation of technical standards to ensure data interoperability and to build trust in data governance amongst EU citizens.

In addition, incidents of data misuse by commercial parties, including those based outside the EU, increase the awareness that compliance with data protection rules must be ensured. The challenge for Member States and the EU as a whole is therefore to strike a balance between data security and data sharing, also as the latter is seen as a key requisite for establishing medical innovations, e.g. for vulnerable patient groups such as in specific rare diseases.

While policies and regulations might be regarded as very permissive in some countries, the rules for processing health data in other countries are considered as very stringent, thus impeding information-sharing between healthcare professionals as well as for secondary purposes such as scientific research.

The research concluded that Member States must find a balance between autonomy of citizens and the challenges of their sustainable and safe health care system. It will be interesting to see if in practice member state authorities can achieve full anonymity for health-related data while still keeping the data useful for research. www.lslaw.co.uk | wendylg@lslaw.co.uk

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| news |

Detecting viruses in a pinprick A novel method of detecting viruses in very small volumes has been developed in a collaboration between scientists at Swansea University, Biovici Ltd and the National Physical Laboratory.

Their work – published in Advanced NanoBiomed Research – follows a successful Innovate UK project developing graphene for use in biosensors, devices that can detect tiny levels of disease markers.

For many parts of the world that do not have access to high-tech labs found in hospitals, detecting viruses such as hepatitis C (HCV) could save millions of preventable deaths worldwide. In addition, biosensors like these could be used at the point-of-care – opening effective healthcare in difficult-to-reach settings.

What makes the detection of viruses in such small volumes possible is the use of graphene. It’s extremely thin - only one atom thick - making it very sensitive to anything that attaches to it. By carefully controlling its surface, scientists at Swansea University were able to make the surface of graphene sensitive to the HCV virus. These measurements were done with graphene specialists at the National Physical Laboratory.

In the future, it is hoped that multiple biosensors can be developed onto a single chip, which could be used to detect different types of dangerous viruses or disease markers from a single measurement.

Ffion Walters, Innovation Technologist at Swansea, said: “Highly sensitive and simplistic sensors have never been more in demand with regards point-of-care applications.

Graphene device chip attached to an electrical connector.

This collaborative project has allowed us to realise proofof-concept real-time sensors for HCV, which could be especially beneficial in resource-limited settings or for difficult-to-reach populations.”

Professor Owen Guy, Head of Chemistry at the University, added: At Swansea University, we have now developed graphene-based biosensors for both Hepatitis B and C. This is a major step forward to a future single point of care test” Dr Olga Kazakova, NPL Fellow Quantum Materials & Sensors, concluded: “Participation in this project allowed us to further develop our metrological validation facilities and apply them to the characterisation of graphene biosensors and aid in solving an important challenge in the health sector.”

Superworms have the munchies for polystyrene A species of worm with an appetite for polystyrene could be the key to plastic recycling on a mass scale.

Researchers at the University of Queensland have discovered the common Zophobas morio ‘superworm’ can eat through polystyrene, thanks to a bacterial enzyme in their gut.

The researchers used a technique called metagenomics to find several encoded enzymes with the ability to degrade polystyrene and styrene.

Dr Chris Rinke and his team from UQ’s School of Chemistry and Molecular Biosciences fed superworms different diets over a three-week period, with some given polystyrene foam, some bran and others put on a fasting diet.

The long-term goal is to engineer enzymes to degrade plastic waste in recycling plants through mechanical shredding, followed by enzymatic biodegradation.

“We found the superworms fed a diet of just polystyrene not only survived, but even had marginal weight gains,” Dr Rinke said.

“This suggests the worms can derive energy from the polystyrene, most likely with the help of their gut microbes.”

“Superworms are like mini recycling plants, shredding the polystyrene with their mouths and then feeding it to the bacteria in their gut,” Dr Rinke said.

“The breakdown products from this reaction can then be used by other microbes to create high-value compounds such as bioplastics.”

It’s hoped this bio-upcycling will incentivise plastic waste recycling and reduce landfill.

Co-author of the research, PhD candidate Jiarui Sun, said they aim to grow the gut bacteria in the lab and further test its ability to degrade polystyrene.

“We can then look into how we can upscale this process to a level required for an entire recycling plant,” Ms Sun said.

Dr Rinke said there are many opportunities for the biodegradation of plastic waste.

“Our team is very excited to push the science to make it happen,” he said.

This research has been published in Microbial Genomics.

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| news |

Photons used to create artificial quantum neuron Quantum artificial intelligence edges closer to reality.

Artificial intelligence is used in various applications, such as speech interpretation, image recognition and medical diagnostics.

It has also been shown that quantum technology can be employed to achieve a computing power greater than that of the major supercomputers.

Physicists at the National Research Council (CNR), the Politecnico di Milano and the University of Vienna, have developed a device, called a quantum memristor, which could combine artificial intelligence and quantum computing, opening up as yet unseen potential. The experiment was carried out in an integrated quantum processor, working with single photons.

component with which to build neuromorphic architectures, that is, forged as a model of our brain.

A group of experimental physicists led by Roberto Osellame, research director at the Institute of Photonics and Nanotechnologies of the National Research Council (CNRIFN), and Philip Walther, professor at the University of Vienna, in collaboration with Andrea Crespi, Associate Professor at the Politecnico di Milano, have shown that it is possible to engineer an optical device with the same functional characteristics as the memristor, capable of operating on quantum states of light and thus encoding and transmitting quantum information: a quantum memristor.

Artificial intelligence algorithms are based on mathematical models called neural networks, inspired by the biological structure of the human brain, which is made up of interconnected nodes (neurons). Just as in our brain the learning process is based on the rearrangement of the connections between neurons, artificial neural networks can be “trained” on a set of known data that modify its internal structure, making it capable of performing “human” tasks, such as face recognition, the interpretation of medical images to diagnose diseases and even driving a car. For this reason, research is underway, at academic and industrial level, aiming to obtain integrated and compact devices capable of performing the mathematical operations required for the operation of neural networks in a rapid and efficient way.

“Making such a device is no trivial matter, since the dynamics of the memristor tend to compromise certain advantageous aspects of quantum devices. Our researchers have overcome this challenge by employing single photons (single particles of light) and exploiting their quantum ability to propagate simultaneously in two or more paths,” explains Osellame. “These photons are conducted in what are known as optical circuits, fabricated by means of laser pulses in a glass chip, dynamically reconfigurable, which can support quantum states of superposition on different paths. By measuring the flow of photons propagating on one of these paths, it is possible, through a complex scheme of electronic feedback, to reconfigure the transmission of the device on the other output, and this enables us to obtain a functionality equivalent to that of the memristor.”

A breakthrough in this field was the discovery of the memory-resistor or memristor, a component that changes its electrical resistance based on a memory of the current that passed through it. Scientists have realized that this functioning is surprisingly similar to that of neural synapses, i.e. the connections between neurons in the brain, and the memristor has become a fundamental

“We also simulated an entire optical network made up of quantum memristors,” explains Andrea Crespi, “showing that it could be used to learn both classical and quantum tasks”. This result seems to suggest that the quantum memristor may be the missing link between artificial intelligence and quantum computing.

“Just as in our brain the learning process is based on the rearrangement of the connections between neurons.”

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“Unleashing the potential of quantum resources within artificial intelligence applications is one of the greatest challenges of current research, both in quantum physics and in computer science,” concludes Michele Spagnolo, from the University of Vienna and first author of the scientific publication. “These new results are a step forward towards a future in which quantum artificial intelligence will be a reality.”

Nature Photonics, Volume 16 Issue 4, April 2022. The quantum memristor

| BIOSCIENCE TODAY |

| the big interview |

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| BIOSCIENCE TODAY |

| the big interview |

“Sharks are the oldest vertebrates on the planet with the basic toolbox for an antibodybased immune system.”

Next-generation biologics: today’s reality Shark molecules provide the basis of unique new therapeutics which could transform the treatment of inflammatory diseases and cancer. Karen Southern talks to Dr Caroline Barelle, CEO and founder of Elasmogen, the small biopharmaceutical company behind this potentially huge breakthrough.

Aberdeen-based Elasmogen recently secured £8 million investment for its soloMERTM platform, led by BGF and Scottish National Investment Bank with additional support

from existing investor Scottish Enterprise.

This will enable the company to continue developing its pipeline of next-generation drugs through pre-clinical trials.

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| BIOSCIENCE TODAY |

| the big interview |

soloMERTM is based on molecules naturally found in sharks’ immune systems, which are the equivalent of human antibodies but smaller and more stable. Elasmogen’s pipeline focuses on applying technology to treatments of solid-tumour cancers, systemic inflammatory diseases and inflammatory conditions of the gut.

Their lead programme, partnered with Almac Discovery, is a soloMER-Drug-Conjugate targeting ROR1 in solid tumour cancers This plays into the high growth class of antibody drug conjugates (ADCs), which are gaining interest as a means of developing more targeted cancer therapies.

The technology has roots in the University of Aberdeen where it was established in 2006, before being acquired by US pharma company Wyeth and later by Pfizer. Dr Barelle led the spin-out of Elasmogen and has guided the business since its inception.

TELL US ABOUT YOUR WORK? Elasmogen is a drug discovery and development biotechnology company. We have developed a technology based on antibody-like molecules (we call soloMERs) that form part of the adaptive immune system in sharks and leveraged this platform to bring new therapeutic drugs to the clinic.

WHAT MAKES YOUR SOLOMERTM PLATFORM UNIQUE? There are multiple different factors which together really do enable this technology to overcome some of the limitations of current biologic drugs in the clinic.

One is size – our soloMERs are approximately 10x smaller than classical antibodies, facilitating great tissue penetration, particularly important when you are treating solid tumour cancers. Another key differentiator is how they bind to disease targets – they have a unique shape that enables them to bind into more ‘hidden’, deeper parts of these targets.

In essence, this opens up a greater opportunity to tackle the targets differently. In many cases it delivers a different mechanism of action, which opens up new ways of treating disease. In addition, our soloMERs are single-chain compared to the multiple chained, complex antibodies in the clinic.

Antibodies are designed naturally to bind one target with high affinity and selectivity. Our soloMERs can also achieve this, but critically we can take different soloMERs against different disease targets and link them together to make a single drug. Given the complexity of disease, this ability to re-format rapidly and hit more than one target really makes our technology broad-reaching. So, in a nutshell, this combination of properties make our technology truly unique.

HOW DID IT ORIGINATE? WHAT IS THE SIGNIFICANCE OF THE ‘SHARK’ MOLECULE? It all came about through academic research into the original of adaptive immunity – sharks are the oldest vertebrates on the planet with the basic toolbox for an antibody-based immune system.

As with many animals (particularly ones that have been evolving for over 400 million years!) there are similarities … and there are differences: one of these was the discovery of an antibody-like molecule called New Variable Antigen Receptor or VNAR. These simpler, single chain antibody-like molecules are the foundation for our soloMER technology.

We start by isolating VNARs against disease targets and then ‘humanise’ them, i.e. alter their sequences to make them closer to our naturally occurring antibody molecules and prevent any unwanted immune responses. These humanised clinical candidates are called soloMERs.

Dr Caroline Barelle, CEO of Elasmogen Caroline is CEO and founder of Elasmogen, a company that discovers and develops soloMER biologics for the treatment of inflammatory diseases and cancer. Before establishing Elasmogen, she successfully led teams at Wyeth and subsequently Pfizer in Global Bio-therapeutic Technologies progressing early platform technologies to latestage clinical development. Prior to this she was Alliance and Programs Manager at Haptogen Ltd and a key part of the acquisition team that successfully exited the business to Wyeth Inc. She has been awarded a prestigious Royal Society of Edinburgh Enterprise Fellowship, is a doctoral graduate from the University of Aberdeen in Biochemistry, and an MBA (distinction) from Robert Gordon’s University, Business School. Caroline is a member of the Enterprise Skills and Strategy Board, a member of the Opportunity North East Life Sciences Board, a Senior Associate for the Entrepreneurial Business School, Edinburgh and Entrepreneur in Residence for Queen’s University Belfast. She also sits on the BBSRC FoF and UKRI FLF review panels.

WHAT’S THE POSITION REGARDING PRE-CLINICAL TRIALS? (E.G. SUCCESSES / CHALLENGES) We are currently at late stage pre-clinical with our lead product, which is a soloMER drug conjugate primarily developed for triple negative breast cancer. This has been a great success and enabled us to develop a follow-on pipeline of first-in-class bi-functional drug conjugate drugs.

In addition, we have an incredible anti-inflammatory program which is exploiting the advantages of our technology to target a well-known disease molecule differently, creating a new mechanism of action and hopefully overcoming known issues with the existing portfolio of approved drugs. The main scientific challenges come with having a platform technology with broad reaching-opportunities against many targets for many diseases. Making those choices and balancing the risk within the pipeline (particularly when you are a small biotech company with limited resources) always makes that decision-making process challenging.

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| BIOSCIENCE TODAY |

| the big interview |

WHAT HAS BEEN YOUR MOST SURPRISING FINDING? For me, it’s the constant ability of these domains to bind into different parts (epitopes) of disease targets.

Engineering affinity and improved biophysical properties is a pretty standard process for molecular engineers; however, having a technology that inherently interacts and binds in a different way to different target classes create a real advantage. Coupled with the ease of re-formatting, it offers the ability to make incredibly effective drug candidates.

IS YOUR WORK A GAME-CHANGER FOR CANCER AND OTHER THERAPIES? We certainly hope so, but the proof will only be delivered in the clinic. There are many innovative drugs out there and combining different modalities is a critical approach to treating difficult, complex diseases. Patients are individuals – as are their diseases – so it’s critical that we understand the positive outcomes from our drugs, but are always mindful of limitations and how we can learn, refine and improve our offering to deliver better outcomes.

HOW DO YOU FORESEE ELASMOGEN’S SHORT AND LONG-TERM OUTLOOK, AND POSITIONING IN THE GLOBAL MARKET? We are striving to get our first product into the clinic which is a key inflection point for the technology and the company. We envisage this being a mid-term milestone. In the shorter term we are building our internal pipeline and actively seeking value-adding partnerships where we can combine our technology with others out there to create new drug modalities. There is no question that we are in an incredibly crowded and highly competitive space, so gaining clinical validation is crucial for the technology and for us as a company to gain visibility on a global stage.

a child, I could not understand why my family couldn’t just take him to hospital where a doctor would give him medicine to cure him. Since then, it’s never been the endpoint of medical intervention that has excited me (i.e being the healthcare professional who delivers those medicines) but it’s been the deeper desire to understand the biology of disease and how to design drugs that better serve patients. If I can be a small part of contributing to a drug that makes a difference, then it’s job done for me.

IN YOUR OPINION, WHAT HAS BEEN THE SINGLE MOST IMPORTANT ADVANCE IN BIOPHARMACY IN RECENT YEARS? Goodness, narrowing it down is one is a tough ask. However, for me it’s the switch to understanding the individual disease, the individual patient and designing combinatorial diagnostic and therapeutic approaches that deliver the best opportunity for treatment. I’m afraid that’s a bit of broad stroke but drug design should always have the patient at the centre regardless, right from the beginning.

WHAT IS THE BIGGEST CHALLENGE? Out with all the existing known and unknown challenges and associated risks that come hand-in hand from being a science-based company, for us as a small biotech company in the northeast of Scotland … it’s funding.

ARE THERE ANY OTHER KEY MESSAGES YOU WOULD LIKE TO SHARE?

WHAT HAS BEEN THE MAIN INSPIRATION FOR YOUR WORK?

I consider it a privilege to work in the life sciences sector, particularly in the world of innovative drug design. I get to work with a great team of scientists and meet the most incredible people from all over the world, who ultimately all want to improve the lives of patients. Without question it’s challenging and at times stressful, but the positives far outweigh the negatives, and I wouldn’t change it for the world.

My grandfather suffered with Parkinson’s disease and as

elasmogen.com

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| news |

Drugs first for Parkinson’s and MND in development Novel disease-modifying medicines are being developed to combat debilitating chronic neuro-degenerative disorders.

Neuroscience company NRG Therapeutics Ltd is applying pioneering work in the field of mitochondrial biology to develop first-in-class treatments for Parkinson’s, MND (also known as ALS) and, potentially, other neurodegenerative disorders.

Its approach is based on inhibiting the mitochondrial permeability transition pore (mPTP) in brain cells which has been shown to be neuroprotective in several preclinical models of Parkinson’s and MND. NRG has received a Biomedical Catalyst (BMC) award to fund pre-clinical development of its novel small molecule disease-modifying medicines.

The £2.68 million early-stage BMC award part-funded by the government-backed agency Innovate UK is supporting a 24-month project.

Mitochondria are the powerhouses or batteries of cells and therefore essential for maintaining cell health but there is now a substantial body of evidence showing that mitochondrial failure or dysfunction is common across many degenerative diseases.

million individuals and is the fastest-growing neurological disorder in the world, thus presenting a major healthcare challenge for society.

In addition, NRG is targeting a novel pathological mechanism in MND that was identified in 2020 by its collaborators in Australia. MND is a devastating neurodegenerative disease that typically leads to death within 3-5 years of diagnosis and for which the current gold-standard treatment extends life by ~3 months only.

NRG Therapeutics’ co-founder and CEO Dr Neil Miller, added: “Mitochondrial dysfunction is a common underlying pathology in many degenerative diseases and there is a substantial body of preclinical data available which demonstrates that inhibition of the mPTP in the brain prevents neuronal cell death, reduces neuroinflammation and extends survival in animals. With our unique discoveries, NRG is in a leadership position in this field to develop first-in-class CNSpenetrant mPTP inhibitors”.

The BMC award (of which NRG contributes 30% of the funding) will, over 24 months, advance NRG’s proprietary mPTP inhibitors from lead optimisation through to completion of IND-enabling GLP-toxicology studies with its lead asset.

NRG’s investigational new drugs have been shown in vitro to protect mitochondria and prevent the death of brain cells and therefore have the potential to halt or significantly slow the progression of disease in individuals with Parkinson’s or MND.

Specifically, it will generate a preclinical data package that demonstrates NRG’s drug candidates penetrate into the brain, protect mitochondria, prevent brain cell death in animal models and are safe & well tolerated following chronic dosing.

Dr Arthur Roach, Director of Research at Parkinson’s UK and a Board member of NRG Therapeutics, explained: “What has limited the pharmaceutical industry to date from exploring mPTP inhibitors as novel therapeutic treatments, has been the poor central nervous system (CNS) penetration of known mPTP inhibitors.

It follows an earlier award to NRG of an Innovate UK EDGE grant which provided invaluable scientific and commercial insights for NRG’s MND programme.

“NRG’s small molecules are the first orally bioavailable and CNS-penetrant inhibitors of the mPTP. We are pleased to support NRG in developing its promising discoveries into new drug treatments that could transform the lives of people with Parkinson’s.”

If successful, the project would deliver the first diseasemodifying medicine to halt or slow disease progression for people with Parkinson’s who are currently treated through management of disease symptoms only. PD affects over six

NRG is a private UK company founded by pharmaexperienced biotech entrepreneurs with in-depth knowledge in neuroscience R&D. It has received seed equity funding from the Parkinson’s Virtual Biotech, the drug development arm of Parkinson’s UK and grant funding from The Michael J. Fox Foundation and now, Innovate UK.

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DR NEIL MILLER, CEO & CO-FOUNDER OF NRG THERAPEUTICS

Build your company’s new home at NETPark Phase Three

One of the UK’s premier science parks Design and build opportunities between 5,000 - 50,000 sq ft across 26 acres Ideal for science & technology companies ready to prototype, scale up & manufacture Collaborate on-site with Durham University, 2 Catapult Centres and 3 National Innovation Centres

Join a vibrant community of science, engineering & technology companies making an impact on a global scale.

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| netpark |

NETPark: the hi-tech force for growth in county Durham NETPark of Durham provides world-class laboratory, clean room and office space to science, technology and engineering companies, ranging from start-ups to global AIM-listed firms.

Managed by Business Durham and backed by on-site strategic partner CPI and world Top 100 university, Durham University, this renowned science park fosters, encourages and drives innovation.

Its unique, collaborative eco-system offers a wealth of support and tailored options to meet the needs of businesses throughout Durham.

NETPark is situated in Sedgefield offering a semi-rural campus-style layout, with no traffic congestion and easy access to the A1, Durham City and rail services.

SUPPORT AT NETPARK Business Durham, the business support service for Durham County Council manage NETPark, it offers a variety of support services to businesses on-site, together with partners. Their highly experienced team of professionals help businesses on the park connect to the best funds, expertise and facilities.

Business Durham can also help local business access unique funding programmes to help them grow and develop, including Finance Durham and The County Durham Growth Fund.

CPI manages three national innovation centres on-site: The National Innovation Centre for Printable Electronics, The National Innovation Centre for Formulations, and The National Innovation Centre for Healthcare Photonics.

Durham University offers easy access to facilities, academic expertise and PHD students for NETPark companies.

The university’s building, Orbit, is a hub of innovation for ambitious science and technology companies, which benefit from the thriving community of science and technology-based businesses on-site.

PHASE 3: NEW GROWTH Plans for expansion at NETPark have been approved by Durham County Council Cabinet, which has agreed to invest £50m to finance the provision of up to 270,000 sq ft of new laboratory, office, production and storage space.

NETPark Phase Three consists of up to 12 speculative units from 5,000 sq ft to 35,000 sq ft, which will allow science, engineering and technology companies to grow, scale-up and commercialise their operations.

This initial phase of development is part of larger expansion plan to the park, which includes a masterplan for up to 433,800 sq ft across the 26-acre site, and design and build opportunities up to 80,000 sq ft.

Janet Todd, NETPark Manager said: “It is an exciting time to be at NETPark. Work starts later this year to add 270,000 sq ft of space giving growing companies options to grow on the park when they are ready to scale up operations. Whilst also attracting new businesses to the park to expand our collaborative community.”

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| netpark |

IBEX at NETPark

Kromek: a NETPark pioneer Kromek specialises in CBRN (Chemical, Biological, Radiological, and Nuclear) detection products and services.

The company first spun out of Durham University’s Department of Physics in 2003, with just two employees. Today it is a global OEM, with around 170 employees across the UK and USA, the majority working out of NetPark.

Kromek is a leading developer of high-performance radiation detection products, producing X-ray and gamma ray imaging and radiation detection products for the medical, security screening and nuclear markets. It was floated on AIM in 2014.

WHY NETPARK? Dr Arnab Basu, CEO of Kromek, explains: “As a Durham University spin-out, Kromek’s origins lie in Durham and we regard it as our home.

“NETPark’s high-tech laboratory facilities outside the university environment really gave us credibility in the early days, and we really appreciate the partnership approach that has continued through to our current expansion.

“Having been on NETPark for nearly 20 years, we enjoy the exposure to high tech opportunities and political influences, while maintaining excellent relationships with NETPark and other businesses on the site.

“Kromek grew from two to 30 people inside the incubator; from there NETPark built a bespoke building for us on-site. We then expanded into Explorer 1 as the team grew.

“Being part of a successful community of likeminded people, doing like-minded things, has been a fantastic experience, and allowed us unrivalled access to support and other facilities on the park.

FUTURE PLANS “Kromek is settled here at NETPark, and proud to continue playing a part in County Durham’s success! We fully intend to stay and grow in the region, supporting other local businesses and the community for many more years to come.”

Starting out as a virtual tenant at NETPark, innovative software specialist IBEX moved into bigger, customdesigned office and lab space in 2018, to help double its workforce and transform into a multi-millionpound business.

Founded in 2010, IBEX is on a mission to create a world without fragility fractures through access to earlier and more accessible osteoporosis diagnosis.

Using advanced physics modelling and AI methods, IBEX Trueview® software maximises the value of every medical X-ray to provide new diagnostic outputs and improved image quality for more accurate diagnoses in digital radiography, mammography, and cone-beam computed tomography.

EXCELLENT SUPPORT NETWORK As IBEX expands, Dr Neil Loxley, CEO, praises the expert backing from NETPark and Business Durham, including their extensive support infrastructure, positive staff attitude, and ease of access to space.

WHY NETPARK? Dr Loxley explains: “Having a NETPark address definitely added credibility when we started out as a virtual tenant, and then progressed on to incubator space. We were given the ability to grow with use of both office and custom-built lab facilities.

“As one of the first companies to take space in the Discovery 2 building, we have now taken on more space – and employees – in Explorer.

“Being in a dynamic, innovative atmosphere, surrounded by like-minded companies, has certainly helped, as has the quality of facilities.”

HAVE YOU ACCESSED SUPPORT FROM CPI, DURHAM UNIVERSITY, DCC OR BUSINESS DURHAM? “CPI supported us with development of breast phantoms as well as other ad-hoc support and use of equipment in the earlier days of the company.

“Business Durham support has largely been through rates grants that have helped reduce operating costs as we’ve grown. We’ve also had support from Digital Drive Durham for advanced computer hardware and the Durham Business Recovery Grant, which supported regulatory and market assessment activities.

“Durham Uni has been involved with several grant funded projects as partner but has also supported us with subsidies for internships through the DICE programme and industrial PhD students.”

FUTURE PLANS AT NETPARK? Dr Loxley adds: “Our recent move and associated growth will see IBEX shift into profitability and increase its highly skilled workforce to more than 30 in the coming years.

“NETPark provides excellent facilities for technology start-ups such as IBEX. As the company has grown, we have been able to seamlessly progress from a virtual office through to incubator space and finally into custom-designed office and lab space, all on the same site. NETPark has created a dynamic and thriving technology ecosystem that promotes interaction and collaboration between all its tenants.”

ARNAB BASU, CEO of kromek

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| BIOSCIENCE TODAY |

| work in biotech |

Attitudes to work and reward in biotech have changed - and employers … so must you!

Work in life sciences has never really been about the money, but the mix of qualities that companies offer – and employees want – changes over time. Singular Talent speaks to over 1,500 candidates every year and MD Tom Froggatt has seen the pandemic change what bio-scientists want most from employers.

In talking to candidates, you hear about a lot more than the job. How they got started, where they are in their careers or their lives, their hopes and fears… But over the years we have been tracking the answer to one crucial question: why do you want to change your job?

In November 2021, we listened to bio-science employees of every kind, scientists, lab-based and not, as well as those in commercial and support roles. What we heard showed marked differences in opinion from 2019, the last year we tracked their mood. The most significant shift is at the top of the table, where career progression (previously the most important reason for as many as 40%) dropped to 28%, and learning and development (previously the main reason for only 10%) has doubled to 20%.

What is the main reason for wanting to change your job?

2021

2019

Career progression

28%

40%

Learning and development

20%

11%

Culture and environment

11%

-

Stability

11%

-

Exciting Science

10%

11%

Patient Impact

9%

-

Role, job title, work/life balance, salary, benefits

<1%

<1%

Other highlights were an increased emphasis on company culture and the working environment, and perceptions of overall business stability. Both were largely absent from the previous study, reflecting on the one hand changing priorities and the impact of working from home, and on the other perhaps fears of uncertain times ahead.

Not surprisingly, but always worth remembering, salaries, benefits, and job title remain mere symbols. While they must be reasonable, they are not main motivators for candidates to risk a job change.

WE HAVE SEEN A RISE IN PEOPLE EXPECTING MORE FLEXIBILITY OR WHO FEEL EMPLOYERS HAVE NOT ADAPTED TO THE POST-COVID WORLD It is worth considering the context for these apparent shifts in attitudes as they may be expressive of bigger themes.

The first is the effect of the pandemic on everything from work patterns to personal philosophy; short term or long, it has certainly made us think about what contributes to or detracts from a fulfilling life. Secondly, the tight labour market in life sciences as in other fields is enabling candidates to be more selective - they are able to evaluate companies more critically.

It is tempting to think of COVID as the trigger for a change in attitudes, but it is more likely to be an accelerator of change.

What we have certainly observed in conversations with

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| work in biotech |

candidates is the re-prioritisation of the role of work in their lives, and within work the desirability of different qualities.

This latest set of views might suggest that ambition is not what it was, at least for the moment, and that fulfilment might be found more through continuous learning. In many cases, candidates said there was nothing wrong with their company, but they felt they had stopped developing, which in turn made them decide to leave.

The issues of culture and business stability seem more directly a consequence of companies’ response to the pandemic. We have definitely seen a rise in people expecting more flexibility and many who feel their employers have not adapted well to the post-COVID world. Concern for stability could be a response to something lacking in their lives, or a reflection of the wider economic upheaval.

Greater choice for candidates is giving them bargaining power. We see this all over the place, not only in candidate conversations, but in more tangible ways such as offers and counter-offers.

Tom Froggatt, Singular Talent to approach the subject on an individual level. It helps to understand what people are interested in as well as their strengths and weaknesses. Set budgets for development as a business, of course, but work with individuals to identify and create programs that are meaningful to them as well as broadly more beneficial to the business.

At present it would not be surprising for candidates to hold three or four offers with companies before making a decision. Worse yet for employers, the rate at which candidates decline at the last minute due to counter-offers has more than doubled in the first half of 2022 - generally to stay where they are.

In precarious times, and especially in smaller businesses, stability is hard to cultivate but one thing that helps is communication. Emphasise the value of the work you are doing and the company’s strategies and plans. This is linked to culture and environment, which can be shaped by the management team as much as the employees. It is important that you make the culture apparent to potential hires during the selection/attraction stages, but equally that it remains consistent once they join. All your cultural building blocks such as values and behaviours should be clearly measured and maintained within the business and compared regularly.

HOW CAN YOU ATTRACT THE BEST HIRES AND RETAIN YOUR GOOD PEOPLE? We have not talked much about progression and it remains top of the list, so let’s start there with improvements. It is important for employees to be able to see how they get on, but too often there is ambiguity. Be as clear as you can on what people need to do: requirements, timeframes, the precise competencies expected, and how they are measured. You might consider finding examples of other individuals’ progression or offer mentors to help motivate achievement in others.

For learning and development, the priority is to be ready

In challenging times amid changing attitudes and a difficult market, employers can still do much to attract and retain talent. It’s important to put yourself in your employees’ shoes. Think critically about your culture, environment and how well you communicate. Allied to that is the need to think of employees not as a company but as individuals with definite needs that may vary over time. Be clear about their options for development as well as progression, and find ways to offer support that match different people’s aims.

Lastly, it is vital to keep hearing opinions and think about making improvements to keep your talent advantage intact.

“In many cases, candidates said there was nothing wrong with their company, but felt they had stopped developing, which in turn made them decide to leave.”

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| impact of technology |

Going against the grain What impact could today’s fledgling technologies have on the humans of the future? Laurence Weir, Head of Biomedical Engineering at Plextek, explores the possible implications.

Humans are notoriously bad at predicting the future. We tend to overestimate the impact of technology in the short term and underestimate the effect in the long run. This is because progress is exponential, while our predictions tend to be linear. And it is all but impossible to predict discoveries, what discoveries will make possible, and how they can impact our lives.

However, it is becoming apparent that several technologies, which are in their infancy or early development today, will have dramatic effects on the way we live our lives in future years. Although we cannot predict their consequences, many of us reading this will live to see changes in our lives of greater magnitude than print, the combustion engine, and the internet.

GENETIC ENGINEERING, BIOTECHNOLOGY, MEDICAL TECHNOLOGY We are beginning to sense what may be possible as we move from engineering biological systems and products outside the body to engineering the human body itself. Techniques

like CRISPR and other gene technologies will soon allow us to safely modify the human genome.

Undoubtedly these techniques will be debated, controlled, limited, or possibly even banned completely, but history tells us that sooner or later they will come into use. And as a result, we could see body augmentation capabilities that will enable humans to be smarter, stronger, more capable, or simply just plain different.

Changes in physiology may include everything from modifying hair colour to eliminating specific diseases to increasing muscle size, giving rise to humans that are more resilient, capable, and healthy, leading to a transhuman society in which our human 1.0 bodies have been upgraded to a far more effective human 2.0.

ROBOTICS Robots are already deeply involved in our lives, from industrial automated machines that can rapidly and precisely assemble vehicles to chatbots and other

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| impact of technology |

interactive systems that use conversational interfaces to interact and provide information and assistance.

They are likely to play an increasingly important role in our lives, taking on even more procedures where reliability and precision are important, or where the practice is an unwanted or a dangerous chore for some people, such as cleaning, building maintenance or repairs in a hazardous environment.

As machines become capable of interacting further with the world and with humans (so-called collaborative robots, or ‘cobots’), we are likely to see an increase in their physical support role, for example in the care sector. Robots are also likely to be increasingly used in the delivery of healthcare and in medical operations, where surgical robots can perform extremely precise operations under challenging or hazardous conditions.

It has been suggested that up to 30% of current jobs could be automated through robotic systems by the mid-2030s.

This will lead to a shift in employment for humans into roles where more social and empathic skills are required, such as teaching, caregiving and other emotionally supportive roles.

Similarly, doctors may see a shift from the direct practice of medicine to providers of information, guidance, and support for their patients.

Laurence Weir, Head of Biomedical Engineering , Plextek

ARTIFICIAL INTELLIGENCE This process of the increasing obsolescence of human labour is certain to accelerate through parallel developments in Artificial Intelligence. There are many sectors where AI is already augmenting human capabilities, for example in solving the highly complex challenges of weather forecasting or the impact and amelioration of environmental change. Other sectors include legal processes or medical diagnosis, where deriving insightful conclusions from knowledge of complex data sets is required. But in addition, AI is likely to drive massive innovation in many existing professions and industries, with the potential for creating new jobs in areas that we cannot currently predict.

from data synergies. At some point, they may be capable of passing the Turing test, in which an AI is may be indistinguishable from human intelligence.

NANOTECHNOLOGY Perhaps the area whose impact on the future is least well understood is nanotechnology, the manipulation of matter on a near-atomic scale to produce new structures, materials, and devices with a vast range of applications.

The promise of this technology encompasses medicine, materials, manufacturing, electronics, energy production, and consumer products.

AI systems currently have limitations, in particular relating to their overall flexibility, as they tend to be specialised for particular tasks. That will gradually change as AI systems become capable of processing different types of input and improve their effectiveness at creating real innovation

Unsurprisingly, nanotechnology raises many of the same issues as other new technologies, including concerns about the environmental impact of nanomaterials, and their potential effects on global economics, as well as speculation about various apocalyptic scenarios (the ‘grey goo’).

“Changes in physiology may lead to a transhuman society in which our human 1.0 bodies have been upgraded to a far more effective human 2.0.”

CONCLUSION

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We may not know what lies in our future, but we can be sure that life in 50 years will be radically different from today.

How we, and society at large, adjusts to those changes will define the type of world in which we will live.

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| future of genomics |

Precision breeding for a sustainable future: unpacking the future of genomics Neil Ward, General Manager of PacBio EMEA, examines the potential impact of the UK’s Precision Breeding Bill.

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| future of genomics |

Neil Ward, General Manager of Pacific Biosciences (EMEA)

Genomic sequencing machines are key to helping unlock the secrets of our huge genetic diversity

Genomic sequencing holds the potential to unlock powerful insights that will advance our understanding of all life.

In recent years, governments and national healthcare systems have begun exploring how genomic sequencing can be applied to critical societal issues. We’ve seen this most recently in the UK via the new Genetic Technology (Precision Breeding) Bill. This legislation aims to support the development of crops that will bolster food security in the face of climate change and a growing population.

Precision breeding will be powered by highly accurate long-read genome sequencing, which gives researchers a complete and accurate picture of genetic variation by combining insights from both the genome and the epigenome.

Having this deep foundation of genetic resources will enable researchers to produce higher-yielding, more nutritious foods faster than via traditional breeding. The bill is a step towards being able to sustainably feed the world despite challenging environmental and social circumstances.

ADDRESSING GLOBAL CHALLENGES As the human population continues to grow, so does the pressure on food supply. The demand for more food, combined with the challenges that climate change poses to the agriculture industry are driving innovation in this space. Precision breeding holds the promise of improving nutritional content, and producing anti-allergenic crops that use fewer pesticides and fertilisers and are resistant to climate change.

For millennia, farmers have been attempting to improve the next generation of plants and animals by crossing strains, that have desirable traits, with one another. Since the 1920’s, farmers have accelerated that process in crops by mutation breeding. By exposing plant seeds to chemicals or radiation to induce thousands of random mutations, new varieties of crops with desirable traits were successfully developed.

But this shotgun approach of forcing random mutations also brought with it detrimental changes. Today, modern molecular biology techniques allow much more precise

changes to be made without the accompanying mutations, with the added benefit of being faster than selective breeding.

To be successful in precision breeding, a complete map of the genome is needed to not only identify whether the intended genetic changes have taken place, but also to monitor for the introduction of unintended genomic changes. Highly accurate, comprehensive genetic sequencing is critical for both the initial mapping and quality control when developing new crop varieties.

WHAT’S NEXT FOR GENOMICS? In addition to its potential in fields like agriculture, highly accurate long-read sequencing also holds huge promise in areas including human genomics, microbial genomics, oncology, and gene therapy. But to create a world where everyone can benefit from genomics, we must continue filling the gaps in our knowledge about plants, animals, and humans. It took scientists until 2022 to sequence the first complete human reference genome. Yet as a reference, it fails to represent the huge genetic diversity of humanity and risks further entrenching healthcare inequality. Projects like the Human Pangenome Project, which PacBio is proud to be a member of, are working to address this lack of diversity.

The UK is in a strong position to lead the way in the future evolution of genomics. It has a well-established, pioneering genomics heritage, with a rich history spanning Watson, Crick and Franklin’s discovery of the DNA double helix, Fred Sanger’s pioneering sequencing method and early attempts at cloning such as Dolly the sheep. The country is also paving the way with other projects that will transform our understanding of the natural world, including a plan to map the DNA of all 70,000 species of life on the British Isles.

Fulfilling the promise of such projects and accelerating precision breeding innovation depends on having the most accurate and complete picture of genomic variation as possible. Only then can scientists uncover the complex and unique regions of the genome that until now have been hidden, and use these insights to accelerate scientific discoveries that better human health and the future of our planet.

“The first complete human reference genome was only sequenced this year.”

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| news |

Heparan Sulfate breakthrough in obesity research The 10E4 Heparan Sulfate (HS) antibody has been used in pioneering obesity research to quantify its role in the process of intercellular mitochondria transfer to macrophages.

A red-labelled macrophage in white adipose tissue acquirees green mitochondria from neighbouring cells, including fat cells. Left, low power to show orientation of the macrophage embedded among massive adipocytes. Right, high power to show a macrophage interacting with and internalizing green mitochondria from other cells in the tissue (courtesy: Brestoff Labs.)

In recent published research, researchers from the Washington University School of Medicine demonstrated that adiposetissue resident macrophages acquire mitochondria from adjacent adipocytes using HS. This process occurs in healthy conditions but is impaired in obesity.

They have also shown that genetic disruption of mitochondria uptake by macrophages reduces energy expenditure and increases diet-induced obesity in mice, indicating that intercellular mitochondria transfer to macrophages mediates systemic metabolic homeostasis.

Obesity is an increasingly common metabolic disease that affects over 40% of adults and 18% of children and adolescents in the US alone, and is an independent risk factor for the development of many other disorders such as type 2 diabetes, cardiovascular diseases, and cancer.

Group head, Professor Jonathan Brestoff, said: “Mitochondria are the power plants of cells, and it has long been assumed that they are made in one cell and never leave. We discovered that is not really the case and found that fat cells give some of their mitochondria to an immune cell type called macrophages.

“In obesity, this transferring of mitochondria between cells goes awry, contributing to faster weight gain and worse metabolism. Using a tool called CRISPR, we screened the entire genome and figured out that cells trade mitochondria using a special type of sugar called heparan sulfate, which we think acts like a loading dock for receiving cargo like mitochondria.

“When we delete heparan sulfates on macrophages, mice get fat. This suggests to us that it is probably good for cells to trade mitochondria with each other. Our team is now trying to figure out how this mysterious and surprising process of mitochondria transfer works because we believe we can harness this biology to treat some human diseases.”

Postdoctoral fellow Dr Wentong Jia added: “The cell surface expression of heparan sulfate, a glycosaminoglycan required for mitochondria uptake in macrophages, depends on a key glycosyltransferase named EXT1. The 10E4 antibody from AMSBIO has helped us verify that we’ve successfully prevented Heparan Sulfate from being synthesised in cells that lack EXT1.”

“I find it fascinating that cells use heparan sulfates to take up mitochondria,” says Rocky Giwa, a PhD candidate in the Brestoff Lab. “I wonder if there’s a correlation between the amount or composition of heparan sulfates and a cell’s ability to efficiently take up mitochondria from other cells. Since the various HS antibodies have unique specificities, the different clones can help us start to attack that question.”

Heparan sulfate is a highly sulfated polysaccharide, synthesised as the glycosaminoglycan component of heparan sulfate proteoglycans (HSPGs), that is widely distributed on cell surfaces and basement membranes in mammals. It participates in important biological processes due to it displaying specific interactions with many biologically active proteins. amsbio.com

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| BIOSCIENCE TODAY |

| news |

Deep learning integrated into biomolecule design A pioneering cloud R&D platform for the biotech industry is helping the scientific community better access DeepMind’s AlphaFold.

Benchling has launched the AlphaFold beta feature to overcome challenges of implementation, computing power and resourcing, and make experimentation and integration easier on its platform.

directly within Benchling, but also centralise experimental context, collaborate with teammates, and connect with downstream scientific workflows on a single, secure platform.

AlphaFold is an artificial intelligence program developed

by DeepMind that can predict the 3D structure of a protein from an amino acid sequence with unprecedented accuracy. Not only is it a scientific breakthrough with huge potential, but it is also emblematic of the new era of modern biotech — data-driven, open-sourced, collaborative and ultimately, faster than ever.

“Our team gets excited about two things: science and bringing software to science,” said Ashu Singhal, president and co-founder of Benchling.

“By making AlphaFold available to the biotech industry at the click of a button, scientists will be able to seamlessly experiment with this exciting advancement and find new ways to leverage AlphaFold output in their research.”

ASHU SINGHAL, PRESIDENT & CO-FOUNDER OF BENCHLING Despite this, the vast majority of labs are unable to access AlphaFold today. AlphaFold is open source to use, but setting up the machine learning architecture to run the AlphaFold algorithm is extremely complicated, and takes significant engineering bandwidth to use in a stable, sustainable way.

Born out of a Benchling hackathon, the beta feature allows customers to select any amino acid sequence stored in Benchling, request a 3D structure for it, and visualise the results in its platform. Customers can view and interact with the 3D structures in a Molstar (Mol*) viewer alongside the primary sequence. The structure files (.pdb format) also can be downloaded for more sophisticated modeling using third party applications. Scientists may readily share these protein structure files with other teammates, further extending the reach and utility of the data output.

Now for the first time, with the beta feature, scientists can not only predict 3D structures of novel proteins

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“By making AlphaFold available to the biotech industry at the click of a button, scientists will be able to seamlessly experiment with this exciting advancement and find new ways to leverage AlphaFold output in their research. While the use cases for AlphaFold are still being explored and proven, Benchling’s goal with its beta feature is to support its community.”

EARLY BETA USERS PetMedix, a Cambridge-based veterinary therapeutics biotech, is developing therapeutic antibodies for companion animals.

“PetMedix is developing therapeutic antibodies for companion animals and having the ability to produce AlphaFold structures of our antibodies and antigens allows us to better understand the biology behind them,” said Dr. Albert Vilella, Head of Bioinformatics at PetMedix.

“There have been a lot of technological developments in Artificial Intelligence that are now being applied to answering biological questions in important fields such as immunology. We see this in the literature, for example in the study of COVID19 immune response and antibody design, and we are excited to be able to apply these technologies to our antibodies, so we can help save and improve the lives of animals all over the world.”

| BIOSCIENCE TODAY |

| covid immunity |

COVID-19 deaths among elderly may be due to genetic limit on cell division Your immune system’s ability to combat COVID-19, like any infection, largely depends on its ability to replicate the immune cells effective at destroying the SARS-CoV-2 virus that causes the disease. These cloned immune cells cannot be infinitely created, and a key hypothesis of a new University of Washington study is that the body’s ability to create these cloned cells falls off significantly in old age.

Jake Ellison reports.

According to a model created by UW research professor James Anderson, this genetically predetermined limit on your immune system may be the key to why COVID-19 has such a devastating effect on the elderly.

Anderson is the lead author of a paper in The Lancet eBioMedicine detailing this modeled link between aging, COVID-19 and mortality.

“When DNA split in cell division, the end cap — called a telomere — gets a little shorter with each division,” explains Anderson, who is a modeler of biological systems in the School of Aquatic and Fishery Sciences. “After a series of replications of a cell, it gets too short and stops further division. Not all cells or all animals have this limit, but immune cells in humans have this cell life.”

The average person’s immune system coasts along pretty good despite this limit until about 50 years old. That’s when enough core immune cells, called T cells, have shortened telomeres and cannot quickly clone themselves through cellular division in big enough numbers to attack and clear the COVID-19 virus, which has the trait of sharply reducing immune cell numbers, Anderson said. Importantly, he added, telomere lengths are inherited from your parents.

Consequently, there are some differences in these lengths between people at every age as well as how old a person becomes before these lengths are mostly used up.

Anderson said the key difference between this understanding of aging, which has a threshold for when your immune system has run out of collective telomere length, and the idea that we all age consistently over time is the “most exciting” discovery of his research.

“Depending on your parents and very little on how you live, your longevity or, as our paper claims, your response to COVID-19 is a function of who you were when you were born,” he said, “which is kind of a big deal.”

To build this model the researchers used publicly available data on COVID-19 mortality from the Center for Disease Control and US Census Bureau and studies on telomeres, many of which were published by the co-authors over the past two decades.

Assembling telomere length information about a person or specific demographic, he said, could help doctors know who was less susceptible. And then they could allocate resources, such as booster shots, according to which populations and individuals may be more susceptible to COVID-19.

“I’m a modeler and see things through mathematical equations that I am interpreting by working with biologists, but the biologists need to look at the information through the model to guide their research questions,” Anderson said, admitting that “the dream of a modeler is to be able

“Depending on your parents and very little on how you live, your longevity or, as our paper claims, your response to COVID-19 is a function of who you were when you were born.”

JAMES ANDERSON, modeler of biological systems, the School of Aquatic and Fishery Sciences

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| BIOSCIENCE TODAY |

| covid immunity |

The circles in this illustration represent the immune system’s ageing, in which its ability to make new immunity cells remains constant until a person (represented by the human figures) reaches middle-age or older and then falls off significantly. The central blue figure represents an immune system T cell that attacks the virus. (Michele Kellett and James Anderson/University of Washington).

to actually influence the great biologists into thinking like modelers. That’s more difficult.”

One caution Anderson has about this model is that it might explain too much.

“There’s a lot of data supporting every parameter of the model and there is a nice logical train of thought for how you get from the data to the model,” he said of the model’s power. “But it is so simple and so intuitively appealing that we should be suspicious of it too. As a scientist, my hope

is that we begin to understand further the immune system and population responses as a part of natural selection.”

CO-AUTHORS INCLUDE: Ezra Susser, Mailman School of Public Health, Columbia University; Konstantin Arbeev and Anatoliy Yashin, Social Science Research Institute, Duke University; Daniel Levy, National Heart, Lung, and Blood Institute, National Institutes of Health; Simon Verhulst, University of Groningen, Netherlands; Abraham Aviv, New Jersey Medical School, Rutgers University.

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| BIOSCIENCE TODAY |

| genetic signals |

“Using machine learning, researchers from the University of Sheffield and Stanford Medicine have identified more than 1,000 genes linked to the development of severe COVID-19 cases that required breathing support, or were fatal.”

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| BIOSCIENCE TODAY |

| genetic signals |

Over 1,000 genes linked to severe COVID-19 Researchers from the University of Sheffield and Stanford University in the US have discovered specific genetic signals in people who develop severe coronavirus infection. overlapping the mutations onto the cell-specific genomes the researchers could pinpoint which genes were dysfunctioning and within which cell-types.

Age, body mass index and pre-existing health problems are known to account for some of the disparities, but genetics also play a significant role. The research aimed to address why some people with COVID-19 become seriously ill or die, whilst others have few, if any, symptoms.

RISK GENES

Using machine learning, researchers from the University of Sheffield and Stanford Medicine have identified more than 1,000 genes linked to the development of severe COVID-19 cases that required breathing support, or were fatal. The team was also able to identify specific types of cells in which those genes act up. It’s one of the first studies to link coronavirusassociated genes to specific biological functions.

The researchers also wanted to know which types of cells harboured faulty gene expression. Through their machine learning tool, they determined that severe COVID-19 is largely associated with a weakened response from two wellknown immune cells — natural killer (NK) cells and T cells.

NK cells and a subtype called ‘CD56 bright’ are considered the most important.

Dr Johnathan Cooper-Knock, NIHR Clinical Lecturer in the Department of Neuroscience at the University of Sheffield and co-author of the study, said: “During the research we discovered the genetic architecture underlying coronavirus infection, and found that these 1,000 genes account for three quarters of the genetic drivers for severe COVID-19. This is significant in understanding why some people have had more severe symptoms of Covid-19 than others.”

Dr Cooper-Knock added: “NK cells, which humans are born with and are the body’s first line of defence against infection, are known for their ability to destroy viruses and cancer cells. NK cells also help produce a range of immune system proteins called cytokines. One cytokine, interferon gamma, is a key activator of immune cells. Acting in concert with interferon gamma, NK cells mount an immediate and coordinated defence against viral infections.

The study, published recently in the journal Cell Systems, was led by Senior Author Professor Michael P Snyder from the University of Stanford in collaboration with genetics instructor Dr Sai Zhang and neuroscientist Dr CooperKnock, who is currently a Stanford visiting scholar.

“NK cells are like the generals directing the war. They mobilize other immune cells, telling them where to go and what to do. We found that in people with severe coronavirus infection, critical genes in NK cells are expressed less, so there’s a less robust immune response. The cell isn’t doing what it’s supposed to do.”

RESEARCH PROCESS

Professor Snyder likened COVID-19 risk genes to harmful variants of the BRCA genes that predispose some people to breast and ovarian cancer.

The research team used several large data sets to unpack the genetics behind severe COVID-19. The first data set contained genetic information from healthy human lung tissue. The data helped identify gene expression in 19 different types of lung cells, including epithelial cells that line the respiratory tract and are the first defence against infection.

Professor Snyder said: “Our findings lay the foundation for a genetic test that can predict who is born with an increased risk for severe COVID-19.

“Imagine there are 1,000 changes in DNA linked to severe COVID-19. If you have 585 of these changes, that might make you pretty susceptible, and you’d want to take all the necessary precautions.”

Other data came from the COVID-19 Host Genetics Initiative, one of the largest genetic studies of critically ill coronavirus patients. The researchers looked for genetic clues in the data — DNA mutations, called single nucleotide polymorphisms — that might indicate if someone is at a higher risk for severe COVID-19. They tracked whether some mutations occurred more or less often in COVID-19 patients with severe disease.

Dr Cooper-Knock also noted drugs that kickstart sluggish NK cells are already proposed to treat some types of cancer. “The drugs bind to receptors on the NK cells and trigger them to have a more robust response,” he said. Trials of NK cell infusions for severe COVID-19 are underway.”

Mutations that continued to appear, or were notably absent, in the patients who developed severe COVID-19 suggested those variations might be behind the infection’s severity.

ADDITIONAL CONTRIBUTORS

But genetic mutations on their own can be difficult to interpret. To better understand their findings the team used other data describing which regions of the genome are important for different cell types within lung tissue. By

University of Sheffield; Jackson Laboratory for Genomic Medicine; University of Siena; Azienda Ospedaliero-Universitaria Senese; University Medical Center Utrecht; University of Edinburgh; University of Edinburgh, Western General Hospital; Royal Infirmary of Edinburgh; and the VA Palo Alto Health Care System.

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| news |

The Marie device, designed by Leo Cancer Care.

In situ at the ESTRO conference.

Office chair prototype to radiotherapy revolution?

What began as a loose prototype using an office swivel chair has evolved into a novel way to deliver radiotherapy to cancer patients.

Currently, radiotherapy patients lie down on a flat table while a heavy moving gantry rotates a radiation source around them to direct radiotherapy onto the affected part of the body. As a result, radiotherapy facilities require a lot of complex machinery and radiation screening, making them very large and costly to build.

UK start-up Leo Cancer Care has come up with a new, very simple, approach: move the patient not the radiotherapy source.

Named after the Nobel prize-winning physicist Marie Curie, the Marie™ device sits patients upright and slowly rotates them while they undergo CT scanning followed by beams of radiation delivered from a fixed source. The technology is currently available for proton beam therapy and is also being developed for standard X-ray (photon) therapy.

By sitting up rather than lying down, gravity allows the internal organs to fall more naturally into place and there is less movement and effort when breathing, reducing the chances of damaging healthy tissue. This is particularly important when treating cancers in and around the lungs, prostate, head, neck and breast, where an upright posture can help improve accuracy, minimise side effects and lead to better clinical outcomes.

As well as being a quarter of the size and much less costly than conventional proton beam radiotherapy facilities, Leo’s

“We’ve found this upright position allows for better cardiovascular function as well as more consistent breathing, among other benefits. ” STEPHEN TOWE, ceo, leo cancer care

seated device is more comfortable for patients and helps them feel more in control during their treatment.

“If you need to change a lightbulb, you don’t hold the lightbulb and rotate the house. We’re applying that simple concept to modern radiation therapy,” explains Leo Cancer Care CEO Stephen Towe.

“We’ve found this upright position allows for better cardiovascular function as well as more consistent breathing, among other benefits. But, beyond the clinical benefits, we think patients should be empowered to be upright looking eye-to-eye with their care provider, taking on cancer together,” he adds.

The company is currently working with one of France’s leading cancer hospitals, where dozens of patients have experienced this game-changing upright patient positioning technology as part of an ongoing research agreement.

Leo Cancer Care is part of £48m deal struck to provide the world’s first Leo Cancer Care upright proton beam therapy system to a US integrated healthcare system in Wisconsin. It will be deployed as part of a huge investment in a state-of-theart cancer care centre, due to begin treating patients in 2024.

These upright radiotherapy devices could also help reduce backlogs in cancer care in the aftermath of the COVID-19 pandemic. Leo Cancer Care is seeking regulatory approval, and the technology is currently being explored by the NHS. Leo’s devices could even be placed together with an X-ray radiotherapy source in a mobile truck, making treatment more accessible to patients in remote locations and where there is still relatively little infrastructure to treat cancers that would benefit from radiotherapy.

Professor Thomas ‘Rock’ Mackie is chairman and cofounder of Leo Cancer Care, and an ASTRO Gold Medalwinning radiation oncology researcher. He said: “I look forward to seeing our Marie device enable many more people around the world to access upright radiotherapy and the benefits that it can bring.”

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| BIOSCIENCE TODAY |

| news |

Harmless cells transform into ruthless trained killers Processes in the human body could turn groups of harmless immune cells into ruthless killers, capable of attacking other cells infected with viruses or parasites, and potentially tumour cells, a new study reveals.

Gamma delta T cells were previously thought to be ‘preprogrammed’ to recognise and destroying other rogue cells, but it now appears there are strong similarities between some types of the cells and well-known ‘adaptive’ subsets of conventional T cells.

An international group of researchers from the UK, Australia, China, Netherlands and USA - led by the University of Birmingham - published its findings in Cell Reports, noting strong similarities to conventional adaptive ‘killer’ T cells.

Senior co-author Professor Ben Willcox, from the University of Birmingham, commented: “Human gamma delta T cells have typically been assumed to be preprogrammed, however our study shows that at least in blood, some types mirror the behaviour of conventional T cells – suggesting they can be ‘trained’ to become extremely potent killers once they recognise aberrant target cells - including those infected with viruses, parasites, or possibly tumour cells.

“Our discovery has implications for efforts to develop gamma delta T cells as novel cellular therapies. We hope that it will change the way scientists think about these cells and how they might contribute to the treatment of cancer and infectious disease.”

Funded substantially by a Wellcome Trust Investigator Award, the group examined the profile of gene expression in human gamma delta T cells – showing the cells in a much more ‘adaptive’ light.

Gamma delta cells exist alongside alpha beta T cells and B cells in vertebrates. Researchers have discovered that select human gamma delta T cells appear to

transform their pattern of gene expression to activate a ‘killer’ programme – dependent on their exposure to abnormal target cells, with successful recognition of such targets likely a key factor triggering this transformation and subsequent attack.

An extremely strong similarity to conventional adaptive killer T cells suggests that the unique contribution of gamma delta T cells is not the type of response they ultimately mount – such as killing a target cell - but that they are able to recognise abnormal target cells in a very different way.

This suggests that they can mount unconventional adaptive responses in situations when conventional adaptive T cells cannot: Lead author Jack McMurray, from the University of Birmingham, added: “There are a number of scenarios in which gamma delta T cells may be uniquely suited to respond, due to their unconventional recognition capabilities. These include particular microbial, parasitic and viral infections, and potentially some cancers.

“Our research provides a basis for ongoing studies to understand how such unconventional adaptive gamma delta T cell responses are triggered, and also for efforts to harness such responses to develop new and more effective treatments for infections and cancer.”

“Human gamma delta T cells have typically been assumed to be pre-programmed, however our study shows that at least in blood, some types mirror the behaviour of conventional T cells” PROFESSOR BEN WILLCOX, SENIOR CO-AUTHOR, UNIVERSITY OF BIRMINGHAM

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| BIOSCIENCE TODAY |

| nanochannels |

Nanochannels light the way to new medicine The development of new drugs and vaccines requires detailed knowledge about nature’s smallest biological building blocks – biomolecules. Swedish researchers have devised a new microscopy technique that allows proteins, DNA and other tiny biological particles to be studied in their natural state in a unique way.

A great deal of time and money is required when developing medicines and vaccines. It is therefore crucial to be able to streamline the work by studying how, for example, individual proteins behave and interact with one another.

says research leader Prof. Christoph Langhammer, oft the Department of Physics at Chalmers. He has developed the new method together with physics and biology researchers at Chalmers and the University of Gothenburg.

This new microscopy method from Chalmers University of Technology allows the most promising candidates to be found at an earlier stage. The technique also has the potential for use in conducting research into the way cells communicate with one another by secreting molecules and other biological nanoparticles. These processes play an important role in our immune response, for example.

The method is based on the molecules or particles under study being flushed through a chip containing tiny nano-sized tubes, known as nanochannels. A test fluid is added to the chip which is illuminated with visible light.

The interaction between the light, the molecule and the small fluid-filled channels makes the molecule inside show up as a dark shadow and it can be seen on the screen connected to the microscope. By studying it, researchers can not only see but also determine the mass and size of the biomolecule and obtain indirect information about its shape – something that was not previously possible with a single technique.

REVEALING ITS SILHOUETTE Biomolecules are both small and elusive but vital, since they are the building blocks of every living thing. Researchers currently need to either mark them with a fluorescent label or attach them to a surface to get them to reveal their secrets using optical microscopy.

ACCLAIMED INNOVATION

“With current methods you can never quite be sure that the labelling or the surface to which the molecule is attached does not affect the molecule’s properties. With the aid of our technology, which does not require anything like that, it shows its completely natural silhouette, or optical signature, which means that we can analyse the molecule just as it is,”

The new technique, nanofluidic scattering microscopy, was recently presented in the scientific journal Nature Methods, and has also received acclaim from the Royal Swedish Academy of Engineering Sciences. The innovation is now being championed through start-up company Envue Technologies.

Nanochannels light the way towards new medicine.

(Credit: Chalmers University of Technology | Yen Strandqvist | Daniel Spacek | Neuron Collective).

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| nanochannels |

The chip is secured in a specially adapted optical dark-field microscope and illuminated with visible light. (Credit: Envue Technologies | Maja Saaranen)

“Our method makes the work more efficient, for example when you need to study the contents of a sample, but don’t know in advance what it contains and thus what needs to be marked,” says researcher Barbora Špačková, who during her time at Chalmers derived the theoretical basis for the new technique and then also conducted the first experimental study with the technology.

The researchers are now continuing to optimise the design of the nanochannels to find even smaller molecules and particles that are not yet visible today.

“The aim is to further hone our technique so that it can help to increase our basic understanding of how life works, and contribute to making the development of the next generation medicines more efficient,” says Langhammer.

“The aim is to further hone our technique so that it can help to increase our basic understanding of how life works.”

Prof. Christoph Langhammer, research leader,

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HOW IT WORKS The molecules or particles that the researchers want to study are placed in a chip containing tiny nano-sized tubes, nanochannels, that are filled with test fluid.

The chip is secured in a specially adapted optical darkfield microscope and illuminated with visible light.

On the screen that shows what can be seen in the microscope, the molecule appears as a dark shadow moving freely inside the nanochannel. This is due to the fact that the light interacts with both the channel and the biomolecule. The interference effect that then arises significantly enhances the molecule’s optical signature by weakening the light just at the point where the molecule is located.

The smaller the nanochannel, the greater the amplification effect and the smaller the molecules that can be seen.

With this technique it is currently possible to analyse biomolecules from a molecular weight of around 60 kilodaltons and upwards. It is also possible to study larger biological particles, such as extracellular vesicles and lipoproteins, as well as inorganic nanoparticles.

| BIOSCIENCE TODAY |

| global surveillance model |

A global surveillance model is vital for future pandemic prevention Broad viral surveillance is essential in pandemic prevention to allow for detection of potential threats and the immediate early launch of health protocols against pathogens. Yves Dubaquie, senior vice president of diagnostics, PerkinElmer, Inc., investigates how this could work.

As demonstrated with COVID-19, surveillance efforts have been key in the identification of SARS-CoV-2 variants, helping direct medical aid and related resources where they were needed most. The enduring challenge is the current lack of a universal programme or tool to allow for the realtime viral monitoring needed to prevent outbreaks entirely.

Herein lies the opportunity.

To deliver a global surveillance model for pandemic prevention, international health and scientific communities must continue to work with governments, corporations and other vested interests to advance current efforts to combat the spread of COVID-19. A comprehensive model based on existing and future efforts should follow a three-level approach: hard data from hospitals and labs on confirmed cases population-level screening individual-level screening.

For this model to be effective, it is essential to include confirmatory testing and timely, accurate case reporting, particularly in relation to population-level and individual-level screening.

HARD DATA FROM HEALTH SYSTEMS The hard data from hospitals and labs around SARS-CoV-2 follows very strict and clear criteria established by bodies such as the World Health Organisation (WHO) or the Centres for Disease Control and Prevention (CDC) about which cases should be reported based on morbidity and mortality. Such reports provide a clear picture on the spread of the disease, contributing heavily to local and global surveillance efforts. However, while this data has immense, undeniable value, some outbreaks could be missed if, for instance, people with mild symptoms may decide to isolate and not seek follow-up medical attention - meaning their infection goes unreported. Similarly, asymptomatic individuals may not get tested at all. This is a cofounding parameter to consider during data analysis.

BROAD APPROACH TO POPULATION-LEVEL SCREENING Wastewater surveillance proves a viable and effective method to detect outbreaks as it allows for pathogens to be spotted before a given population presents symptoms, helping to inform fast-response strategies. Researchers at the University of California in San Diego recently published findings from a study that asserts wastewater genomic surveillance is a scalable solution that allows for early detection of SARS-CoV-2 variants. Their team uncovered

wastewater spikes that reflected an uptick in confirmed COVID-19 cases in the population studied, and potential SARS-CoV-2 variants of concern weeks before they showed up in the clinical genomic surveillance setting.

In England, the UK Health Security Agency (UKHSA) led the Environmental Monitoring for Health Protection (EMHP) SARS-CoV-2 wastewater monitoring programme, paused at the end of March 2022, which provided coverage of approximately 74% of the population. The programme helped identify not only where the virus was circulating, but also detected mutations, including those associated with known variants of concern (VOCs) and variants under investigation (VUIs). UK-wide wastewater monitoring was also delivered through coordination between the EMHP team and other programmes in the devolved administrations. Deployed at a global scale, wastewater monitoring efforts such as this could be an extraordinary alert mechanism – helping protect against new variants of existing viruses and other potential threats.

With continued improvements in this PCR-based method for surveillance, wastewater analysis has the capacity to target hotspots of interest, such as areas prone to zoonotic spillover, specific communities, or an even more targeted approach (e.g., focus on homes for the elderly). Zoonotic spillover deserves special attention, as most human infectious diseases (60 to 75%) are derived from pathogens that originally circulated in non-human animal species. In the U.S., the Oklahoma Pandemic Center for Innovation and Excellence (OPCIE) was organised to focus on the entire ecosystem (i.e., humans, animals, and the environment), to study the COVID-19 pandemic and prepare for emerging ones, using a multi-omics approach. The state’s public health lab within the OPCIE uses state-of-the-art automated technology to monitor, research, and address public health concerns before they arise.

INNOVATION IN INDIVIDUAL-LEVEL SCREENING The next generation of individual surveillance tools and technologies needs to be inexpensive, non-invasive and digitally reportable to increase the chances of a truly global adoption. Sonde Health, for example, offers a mobile app that analyses a user’s voice to detect subtle changes associated to a number of potential health concerns, ranging from respiratory infections to neurological disease.

Wearable devices, such as smart watches with temperature sensors and blood pressure monitoring capabilities, could also become useful devices for simple daily screening.

Easy-to-access tools that monitor key biomarkers could be especially promising in the surveillance quest for pandemic

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| BIOSCIENCE TODAY |

| global surveillance model |

preparedness – if they are deployed globally and there is a broad uptake. This becomes a challenge when considering rural and remote communities, particularly in low and middle-income countries.

IMPROVING ACCESS TO CONFIRMATORY TESTING As with SARS-CoV-2 surveillance efforts, follow-up confirmatory testing should take place once a person or group are likely to have been infected. This would, of course, be applicable to potential cases detected via the screening methods mentioned previously.

Confirmatory testing must be accessible to all people, and neither cost nor availability should be limiting factors. To improve access and circumvent supply chain issues experienced with global distribution of COVID-19 tests, public and private sector groups could make contingencies to support local manufacturing and stockpiling of test materials. In a future pandemic scenario, once a virus is identified, resources would already be on-hand and more readily available to manufacture the tests needed to detect it.

“At a global scale, wastewater monitoring efforts … could be an extraordinary alert mechanism.”

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REPORTING AND INFORMATION SHARING Indisputably, data is an extremely important element of surveillance programmes. The fact remains that there is no clear knowledge about how well data is being reported. While wastewater analysis or innovative individual screening methods could become increasingly reliable and widespread surveillance methods in the future, a robust reporting system should also be deployed to achieve success.

IT solutions such as contact tracing apps rely on accurate data reporting to effectively monitor and control the spread of COVID-19 and will be a key element of future surveillance models. To be successful, these too require quality data.

Another aspect worth highlighting in this context – in terms of data gathering, analysis and sharing – is the importance of having fully integrated, connected departments working towards the same goal. In this respect, having nationalised health systems, such as the NHS, could be advantageous.

CONCLUSION While we may still have a long road ahead before we manage to put together all the elements needed for a global surveillance model, the efforts deployed across the world during the COVID-19 pandemic provide a strong foundation for it. Ensuring that every country in the world has access to population and individual-level screening tools like those described here will certainly be a challenge for international health and scientific communities to overcome.

| BIOSCIENCE TODAY |

| maternal microbiome |

Maternal microbiome promotes baby’s healthy development Researchers studying mice have found the first evidence of how a mother’s gut microbes, the maternal microbiome, can help in the development of the placenta, and the healthy growth of the baby.

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| maternal microbiome |

Scientists from the Quadram Institute, University of East Anglia and University of Cambridge found that a species of gut bacteria, known to have beneficial effects for health in mice and humans, changes the mother’s body during pregnancy and affects the structure of the placenta and nutrient transport, which impacts the growing baby.

The bacteria, Bifidobacterium breve, is widely used as a probiotic, so this study could point to ways of combating pregnancy complications and ensuring a healthy start in life across the population.

Microbes in our gut, collectively called the gut microbiome, are known to play a key role in maintaining health by combating infections and influencing the immune system and metabolism of the host’s body. They achieve these beneficial effects by breaking down food in our diet and releasing active metabolites that influence cells and body processes.

Scientists are now starting to unpick these metabolitemediated interactions between microbes and the body from birth through to how they affect ageing, but so far little is known about how these influence fetal development and baby’s health pre-birth. The growing fetus receives nutrients and metabolites from its mother, but to what extent those metabolites are influenced by the maternal microbiome, and how this influences pregnancy, haven’t been explored.

To address this, Professor Lindsay Hall from the Quadram Institute and University of East Anglia and Dr Amanda Sferruzzi-Perri and Dr Jorge Lopez-Tello from the University of Cambridge, analysed how supplementation with Bifidobacterium breve affected pregnancy in mice.

Prof. Hall has been studying Bifidobacterium and the microbiome in very early life, previously showing how providing specific probiotics can help premature babies.

These bacteria rise in numbers in the microbiome during pregnancy in humans and mice, and alterations in its levels have been linked to pregnancy complications.

Bifidobacterium breve, a key member of the maternal microbiome. Credit: Hall Lab, Quadram Institute. providing Bifidobacterium breve to germ-free mice improved fetal outcomes by restoring fetal metabolism, growth and development to the normal levels.

Lacking the maternal microbiome also hampered the growth of the placenta in a way that would affect fetal growth, and more detailed analysis identified a number of key cell growth and metabolic factors that appear to be regulated by the microbiome and Bifidobacterium breve.

“The placenta has been a neglected organ despite it being vital for the growth and survival of the fetus. A better understanding of how the placenta grows and functions will ultimately result in healthier pregnancies for mothers and babies,” said Dr Lopez-Tello.

The researchers also found that the microbiome affected key nutrient transporters, including those for sugars within the placenta that would also influence the growth of the fetus.

Dr Amanda Sferruzzi-Perri said: “Pregnancy disorders affect around one in ten pregnant women. This is worrying as pregnancy complications can lead to health problems for the mother and her baby even after the pregnancy. “

“Our findings reveal that the maternal microbiome promotes development of the placenta and growth of the fetus.” said Prof. Hall.

“This study carried out in mice, identifies a new player in the communication between mother, placenta and fetus, which is the maternal microbiome. Finding out how this form of communication works and how to improve it may help many women who develop pregnancy complications, as well as their developing child.”

“We think that this is linked to the altered profile of metabolites and nutrients, which affects nutrient transport from mother to baby across the placenta. Excitingly it appears that adding in a probiotic Bifidobacterium during pregnancy may help to boost how the placenta functions, which has positive effects on the baby’s growth in utero”

Germ-free mice can be bred lacking any microbes, allowing comparisons with other mice that have a “normal” microbiome. These comparisons provide valuable insights into the role of the microbiome in health and such studies can’t be carried out in humans.

These findings are strong indicators of a link between the microbiome of the mother and the development of the baby, but in this first study of its kind there are limitations.

In this study, which was funded by the Wellcome Trust and the Biotechnology and Biological Sciences Research Council, they also looked at the effect of feeding germ-free mice the probiotic Bifidobacterium breve.

Their findings are published in the journal Cellular and Molecular Life Sciences and show that the maternal gut microbiome and Bifidobacterium breve specifically, have a role in regulating fetal growth and metabolism.

In the germ-free mice, the fetus did not receive adequate sugar and failed to grow and develop properly. Excitingly,

“Our findings reveal that the maternal microbiome promotes development of the placenta and growth of the fetus.”

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This study focused on one single bacterial species, and whilst this showed that Bifidobacterium breve had positive effects on germ-free mice during pregnancy, this is not a natural situation. Future studies are needed to confirm these effects in a more natural and complex microbiome.

The study was carried out in mice and cannot automatically be translated into treatments for humans. The knowledge provided in this proof-of-concept animal study is critical for guiding future studies in humans that will uncover whether the human maternal microbiome has similar effects.

Certainly, if that is the case, it could provide a relatively simple and low-cost way to help improve pregnancy outcomes with positive benefit for the life-long health of the mother and her child.

REFERENCE Maternal gut microbiota Bifidobacterium promotes placental morphogenesis, nutrient transport and fetal growth in mice. Jorge Lopez-Tello, Zoe Schofield, Raymond Kiu, Matthew J. Dalby, Douwe van Sinderen, Gwénaëlle Le Gall, Amanda N Sferruzzi-Perri, Lindsay J Hall was published in Cellular and Molecular Life Sciences on 28th June 2022. DOI : 10.1007/s00018-022-04379-y

| BIOSCIENCE TODAY |

| news |

Investigational drug fosters nerve repair after injury

Regenerating damaged nerves.

Credit: Magicmine.

Scientists from the University of Birmingham have shown that a brain-penetrating candidate drug currently in development as a cancer therapy can foster regeneration of damaged nerves after spinal trauma.

The research, published in Clinical and Translational Medicine, used cell and animal models to demonstrate that when taken orally the candidate drug, known as AZD1390, can block the response to DNA damage in nerve cells and promote regeneration of damaged nerves, so restoring sensory and motor function after spinal injury.

The announcement comes weeks after the same research team showed a different investigational drug (AZD1236) can reduce damage after spinal cord injury, by blocking the inflammatory response. Both studies were supported by AstraZeneca’s Open Innovations Programme, which shares compounds, tools, technologies and expertise with the scientific community to advance drug discovery and development.

AZD1390 is also under investigation by AstraZeneca to block ATM-dependent signalling and repair of DNA double strand breaks (DSBs), an action which sensitizes cancer cells to radiation treatment. The DNA Damage Response system (DDR) is activated by DNA damage, including DSBs in the genome, which occur in several common cancers and also after spinal cord injury.

Professor Zubair Ahmed, from the University’s Institute of Inflammation and Ageing and Dr Richard Tuxworth from the Institute of Cancer and Genomic Sciences hypothesized the persistent activation of this system may prevent recovery from spinal cord injury, and that blocking it would promote nerve repair and restore function after injury.

“This is an exciting time in spinal cord injury research with several different investigational drugs being identified as potential therapies for spinal cord injury. “ PROFESSOR ZUBAIR AHMED, University’s Institute of Inflammation and Ageing

Their initial studies found that AZD1390 stimulated nerve cell growth in culture, and inhibited the ATM protein kinase pathway - a critical biochemical pathway regulating the response to DNA damage.

The researchers then used animal models to investigate the effect of AZD1390 following spinal cord injury. Here they showed that oral treatment with AZD1390 resulted in significant suppression of the ATM protein kinase pathway, nerve regeneration beyond the site of injury, and the ability of these nerves to carry electrical signals across the site of the injury.

Professor Ahmed commented: “This is an exciting time in spinal cord injury research with several different investigational drugs being identified as potential therapies for spinal cord injury. We are particularly excited about AZD1390 which can be taken orally and reaches the site of injury in sufficient quantities to promote nerve regeneration and restore lost function.

“Our findings show a remarkable recovery of sensory and motor functions, and AZD1390-treated animals being indistinguishable from uninjured animals within 4 weeks of injury.”

Dr Tuxworth added: “This early study shows that AZD1390 could be used as a therapy in life-changing conditions. In addition, repurposing this existing investigational drug potentially means we can reach the clinic significantly faster than developing a new drug from scratch.”

University of Birmingham Enterprise has filed a patent application covering inhibition of the ATM/Chk2 DNA damage response pathway by compounds such as AZD1390, that may represent a potential therapeutic strategy to foster nerve repair.

Ahmed Z, Tuxworth RI. The brain penetrant ATM inhibitor, AZD1390, promotes axon regeneration and functional recovery in preclinical models of spinal cord injury. Clin Transl Med. 2022;4(6):eaat1719. doi:10.1002/ctm2.962

42

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74.9216

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82

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58.6934

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101.07

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58.933195

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186.207

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47.867

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132.9054

87

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44.955912

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