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Tackling the Translational Gap with Whole-Organism HTS

Tackling the Translational Gap with Whole-Organism HTS

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Tackling the Translational Gap with Whole-Organism HTS

We’re screening faster than ever, but are we screening smart? 

High-throughput screening (HTS) has revolutionised early-stage drug discovery. It enables teams to screen hundreds of thousands of compounds at speed, helping to identify and generate leads, before high-cost pre-clinical studies. But despite its scale, HTS often hits a wall. Compounds can look undeniably promising in vitro, however, they can underperform or fail completely, down the line during in vivo studies. The root issue? A lack of biological context. This can cause drug development to be extremely costly and time-consuming, with the average cost for developing a drug being $2.6 billion and taking 10-15 years to get to market [1, 2]. As drug discovery teams face growing pressure to de-risk pipelines earlier, and avoid costly downstream failures, there’s a growing need for methods that combine HTS efficiency with physiological relevance, without sacrificing throughput. 

Current HTS Models: Strengths and Shortcomings 

HTS remains a vital tool in early drug discovery, particularly through two dominant strategies: biochemical (target-based) assays and cell-based phenotypic screens. Biochemical assays allow researchers to assess compound activity against defined molecular targets with high precision. They are designed to detect direct interactions such as enzyme inhibition, receptor binding, or modulation of specific signalling components, and their strength lies in target specificity, quantifiability, and scalability [3.]. When the underlying disease mechanism is well understood, target-based assays offer a streamlined path from screen to lead optimisation, however, the lack of biological context can lead to downstream failure, when tested in more complex environments. 

Cell-based models, on the other hand, offer a way of identifying phenotypic effects, adding another layer of biological relevance. They offer the ability to measure compound effects on more complex cellular behaviours within a living cellular context [4]. Both approaches benefit from automation, cost-efficiency, and clear readouts, making them ideal for large-scale compound libraries. 

For all their advantages, however, traditional HTS models often fall short when it comes to biological complexity. Isolated targets may not reflect the broader context of human physiology, and even cellular systems fail to capture whole-organism interactions [5].  

The Translational Gap 

Despite advances in HTS technologies, a persistent challenge in drug discovery remains: the translational gap. Promising hits identified in biochemical or cell-based assays often fail to demonstrate efficacy or safety in animal models or human trials. This gap stems largely from the lack of systemic context in early-stage models. While these platforms are excellent for understanding molecular interactions or cellular phenotypes, they rarely capture the complex interactions between tissues, organs, and metabolic processes that define disease progression in living organisms [6]. 

For example, a compound may show potency in isolated cells but be rendered ineffective in vivo due to poor absorption, rapid metabolism, or unintended effects on other systems. This is especially true for diseases involving ageing, neurodegeneration, or metabolic dysfunction, where whole-organism dynamics are crucial. As a result, pharmaceutical teams are often forced to rely on costly, time-consuming in vivo studies later in the pipeline to validate findings, by which point major resources have already been committed.  

This disconnect can cause high attrition rates and inflates R&D timelines. The ideal solution would be a screening platform that offers both biological relevance and scalability, enabling earlier identification of candidates with true translational potential, before committing to resource-intensive downstream development. 

C. elegans as a Whole-Organism HTS Tool 

The nematode Caenorhabditis elegans (C. elegans) has long been a valuable tool in biological research. As one of the first multicellular organisms to have its genome fully sequenced, it has contributed significantly to our understanding of development, neurobiology, and ageing. With a short lifecycle, transparent body, and a fully mapped nervous system, C. elegans offers a rare combination of genetic tractability, experimental speed, and whole-organism insight. 

Importantly, around 60–80% of human disease genes have homologues in C. elegans, making it a powerful model for exploring conserved pathways in areas such as neurodegeneration, metabolic dysfunction, mitochondrial disorders, and lifespan regulation [7]. The worm’s simplicity does not come at the expense of biological relevance. It has a nervous system, a well-characterised muscle system that shares features with more complex animals, a digestive tract, and complex behavioural outputs that can be quantified in response to drug exposure.  

Historically, however, the C. elegans model has been underutilised in drug discovery pipelines, largely due to perceived limitations in throughput and automation. However, their ability to thrive in liquid culture, paired with recent technological advances, has now made scalable, phenotypic screening in C. elegans not only possible but practical, opening new doors for early-stage in vivo testing [8]. 

Bridging the Gap with Our Platform 

At Magnitude Biosciences, we’ve harnessed the well-established biological advantages of C. elegans to develop a high-throughput screening (HTS) platform tailored for the demands of modern drug discovery. VivoScanTM , our liquid-based C. elegans screening system, enables the efficient testing of large compound libraries at scale, providing whole-organism, functional readouts that go beyond what traditional cell-based or biochemical assays can offer. 

By introducing in vivo screening earlier in the pipeline, our platform helps teams identify promising targets and compounds with greater biological context, improving the chances of translational success. Positive hits from VivoScanTM can be prioritised with higher confidence before moving into mammalian models, reducing risk, cost, and time in early-stage development. Because C. elegans is a non-protected species under most regulatory frameworks, this approach also avoids the ethical and logistical challenges associated with vertebrate studies. 

Our HTS workflow provides lifespan and healthspan data captured across multiple timepoints, enabling you to monitor treatment effects dynamically over the worm’s lifecycle. This makes it possible to detect both acute and long-term compound effects, further enhancing decision-making during hit selection. For teams looking for lead optimisation, our proprietary WormGazer™ platform adds another level of resolution. WormGazer™ uses advanced imaging and analysis tools to quantify healthspan, locomotion, and cognitive-like behaviours over time, revealing the biological impacts of candidate compounds. 

Together, our platforms offer a scalable, biologically rich, and cost-effective solution to streamline early-stage discovery and improve the likelihood of identifying translatable drug candidates faster and with greater confidence. 

Rethinking Where in vivo Belongs 

Why wait for in vivo testing when early whole-organism screening can give you invaluable insight from the first hurdle? VivoScanTM delivers scalable, biologically rich data, capturing the systemic effects missed by traditional screens. If you’re looking for truly translatable discovery data, at scale, the worm is the way to go. 

References 

  1. Deloitte. Global pharma companies’ return on R&D investment increases after record low | Deloitte UK [Internet]. www.deloitte.com. 2024.
  2. MS Trust. Drug development process [Internet]. MS Trust. 2021.
  3. Zhu Z, Cuozzo J. Review Article: High-Throughput Affinity-Based Technologies for Small-Molecule Drug Discovery. Journal of Biomolecular Screening. 2009 Dec;14(10):1157–64. 
  4. An WF, Tolliday N. Cell-Based Assays for High-Throughput Screening. Molecular Biotechnology. 2010 Feb 12;45(2):180–6. 
  5. Swinney DC, Anthony J. How were new medicines discovered? Nature Reviews Drug Discovery. 2011 Jun 24;10(7):507–19. 
  6. Seyhan AA. Lost in translation: the valley of death across preclinical and clinical divide – identification of problems and overcoming obstacles. Translational Medicine Communications [Internet]. 2019 Nov 18;4(1).
  7. O’Reilly LP, Luke CJ, Perlmutter DH, Silverman GA, Pak SC. C. elegans in high-throughput drug discovery. Advanced Drug Delivery Reviews. 2014 Apr;69-70:247–53. 
  8. Kaletta T, Hengartner MO. Finding function in novel targets: C. elegans as a model organism. Nature Reviews Drug Discovery. 2006 Apr 21;5(5):387–99. 
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VivoScan Data Insight Pack

VivoScan Data Insight Pack

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One response to “VivoScan Data Insight Pack”

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Video

WormGazer™ Video: Reproductive Toxicity of Etoxazole in C. elegans

WormGazer™ Video: Reproductive Toxicity of Etoxazole in C. elegans

Video

The technology developed by Magnitude Biosciences images the movement of worms on several petri dishes at once. On the right you can see a control dish with a single C. elegans worm and another with a worm exposed to the acaricide etoxazole. The white tracks show the movement of the worms, that are the progeny of the original animal.

You will see that in the presence of etoxazole, there are far fewer worms. The graph on the left shows the increase in worm population over time as the experiment progresses. Increasing doses of etoxazole reduce the population size. The bar graph compares the area under the curves to give a quantitative measure of reproductive toxicity. This dataset can be further analysed to measure the rate of population growth and reveal delays in the onset of egg-laying.

https://www.youtube.com/watch?v=G5dECtE3O74

Video

WormGazer™ Video: C. elegans Mobility Decline

WormGazer™ Video: C. elegans Mobility Decline

Video

Ageing is a complex and heterogeneous process and is best studied using natural models of ageing in whole organisms and large test populations. C. elegans is a proven model in many fields of biology including ageing, where major breakthroughs have occurred by identifying mutants and interventions that increase lifespan.

To evaluate and develop therapies that delay ageing or degenerative disease, we need to measure their effect on physiological decline in an ageing model. The nematode worm C. elegans slows down within days of reaching adulthood and this video shows an automated method to quantify that decline developed by Magnitude Biosciences.

https://www.youtube.com/watch?v=lpFxIpKQCk4

The automated technology continually monitors large numbers of C. elegans worms without disturbing them, working out how many worms on each of several petri dishes are moving during a 160 second interval every 5 minutes. In this video, you can see the movement of a wild type C. elegans strain and a strain that has been modified to express the human amyloid peptide (Aβ 1-42) as a model for Alzheimer’s disease.

On the right, you can see the movement of worms on two of many petri dishes on which the worms are cultured. The white tracks are the current movement of the worms, the red colour indicates past movement. You can clearly see more movement with the wild type strain compared to the Alzheimer’s disease model.

One the left is a graph of the proportion of worms moving in the population with time. You can see that a smaller proportion of the disease worms are moving from the beginning and their movement declines quickly with time. For the wild type strain, movement peaks around day 2 and then starts to decline but much more slowly than the disease model worms.

The difference between these strains can be quantified by comparing the area under the curves as shown in the bar graph, which shows how long the average worm stays moving, a measure of healthspan.

NewsPress Release

Magnitude Biosciences secures over £700,000 to accelerate in vivo high-throughput drug discovery platform

Magnitude Biosciences secures over £700,000 to accelerate in vivo high-throughput drug discovery platform

NewsPress Release

Magnitude Biosciences, a specialist contract research organisation (CRO) in County Durham offering in vivo discovery of treatments for age-related conditions and other diseases using C. elegans, has secured over £700,000 in combined funding to scale up its high-throughput screening (HTS) platform.

The investment was led by Maven’s managed regional funds including NPIF II - Maven Equity Finance, which is managed by Maven as part of the Northern Powerhouse Investment Fund II, the Finance Durham Fund, established by Durham County Council and overseen by Business Durham, as well as continued support from existing investors Northstar Ventures. The investment was matched with grant funding from Innovate UK through the Investor Partnerships: Digital Technologies North East programme.

This funding will enable Magnitude Biosciences to enhance its proprietary WormGazer® technology, integrating robotics, machine learning, and liquid culture systems to create a novel HTS platform capable of screening thousands of compounds per week. By rapidly analysing whole-organism data with advanced machine-learning technology, this platform enables pharmaceutical, nutrition, and health supplement companies to quickly identify compounds that may support healthier aging—accelerating discovery, lowering costs, and reducing reliance on traditional animal models.

The expansion will create high-skilled jobs in robotics, software engineering, and biological sciences at the company’s base in NETPark (Sedgefield) strengthening the North East’s reputation as a growing hub for digital and life science innovation

We’re incredibly grateful for the support from Innovate UK, Maven and Northstar as we scale our HTS platform,” said Dr Fozia Saleem, CEO of Magnitude Biosciences. “This funding accelerates our mission to revolutionise drug discovery bringing life-changing therapies to patients faster, cutting costs and timelines, and transforming how we tackle the world’s toughest-to-treat diseases while reducing dependence on traditional animal models.”

Magnitude Biosciences is building the kind of scalable, high-impact technology we look for at Maven, their HTS platform addresses a real need in early drug discovery,” said Michael Dickens, Investment Manager at Maven Capital Partners. “Fozia is also an excellent role model for the region, through her work at Magnitude and as the Vice Chair of the Lifted Project Newcastle Board, where she is helping drive greater investment into female led businesses. We are delighted to support Fozia and her team on their exciting journey.”

The North East is increasingly becoming an epicentre for innovation in the UK and Magnitude Biosciences is a good example of the technology-enabled businesses that NPIF II is able to champion.”, added Sarah Newbould, Senior Investment Manager at British Business Bank. “Empowering female leaders in the science and technology space is also crucial to enabling a more diverse and prosperous economy. We’re excited to see the impact the business will achieve, creating jobs in the region and furthering the important work they are committed to.”

 “Magnitude Biosciences is a fantastic example of the type of innovative, high-growth business that Finance Durham was established to support,” said Kerry Walker, Business Growth Director at Business Durham: “We’re proud to back their continued development at NETPark, where they are not only scaling cutting-edge drug discovery technologies but also playing a vital role in the strength and vibrancy of the science park community.”

We’re proud to continue supporting Magnitude Biosciences alongside Innovate UK as they bring their next-gen screening platform to market,” said Alex Buchan, Investment Director at Northstar Ventures. “The North East is fast becoming a hub for digital and life sciences innovation, and this project adds to that momentum.”

Magnitude’s HTS platform will allow companies to test large compound libraries at speed and scale, creating a step-change in the generation of preclinical in vivo data for the selection of compounds for discovering new therapeutic drugs. With initial pilot work already underway with top-10 pharma clients, the new funding will help Magnitude Biosciences scale delivery, grow its team, and expand its impact on drug development.

The grant funding was awarded under Innovate UK’s Investor Partnerships - Digital Technologies North East competition, which aims to connect ambitious UK businesses with aligned private capital. Magnitude Biosciences’ selection for the programme reflects the strategic importance of its work in enabling scalable, ethical, and cost-effective early-stage drug discovery

For more information on our HTS assay. click here, or get in touch.

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Article

C. elegans: a Game Changer for Scalable Gut-Brain Axis Research

C. elegans: a Game Changer for Scalable Gut-Brain Axis Research

Article

C. elegans: a Game Changer for Scalable Gut-Brain Axis Research

How the Gut-Brain Axis is Shaping the Future of Nutraceutical Research 

What if the key to a sharper mind and a happier mood wasn't in your head, but in your gut? Could the answer to understanding this link lie within a tiny transparent worm?  

The gut-brain axis is a complex, two-way communication system between the gut and the brain, involving neural, hormonal, immune, and microbial signalling. Growing evidence is showing that gut microbes and their metabolites can heavily influence brain function, mood, and behaviour. Market momentum around the gut-brain axis is unmistakable: Google searches for “gut health” increased 35.4% in 2024 vs 2023, and analysts project the digestive-health market to soar from ≈ US $38 billion in 2019 to nearly US $72 billion by 2027. Dedicated human-microbiome solutions, including psychobiotics, are on an even faster track, forecast to jump from US $0.5 billion in 2023 to US $2.8 billion by 2030 (≈28 % CAGR).1 

This surge has spurred a wave of products explicitly targeting the gut-brain axis. Consumer examples include Zenflore® (PrecisionBiotics) with Bifidobacterium longum 1714 for stress resilience, and Bio-Kult Mind (ADM/Protexin) pairing Bacillus subtilis PXN 21 with zinc for cognitive support. On the B2B side, Lallemand’s Cerebiome® (L. helveticus Rosell-52 + B. longum Rosell-175) and Probi’s Sensia™ built around the HEAL9 strain offer finished-product manufacturers documented psychobiotic ingredients for mood, sleep and memory formulations. 

Evidence is building, and clinical studies show B. longum 1714 dampens stress-related brain activity, Cerebiome® lowers anxiety scores and cortisol, HEAL9 improves working memory and sleep quality, and the prebiotic B-GOS reduces the cortisol awakening response after just three weeks. Yet most trials still involve fewer than 120 participants, run for only 2–8 weeks, and provide limited mechanistic insight - leaving regulators cautious. 

For the nutraceutical industry, there is a clear need for faster, scalable tools to unlock the potential of gut-brain axis research. Caenorhabditis elegans, the nematode worm, could be the answer to solving this problem. 

What Makes C. elegans Such a Good Model? 

At first glance, Caenorhabditis elegans (C. elegans), a one-millimetre-long nematode, might not be an obvious choice for gut-brain axis research. However, this simple organism shares some surprising biological similarities with humans that make it ideal for translational research. The C. elegans neuronal network uses key neurotransmitters like serotonin, dopamine, and GABA, which are central to gut-brain communication in humans. C. elegans has a fully-mapped nervous system, allowing us to track and monitor its activity with high precision, linking specific neuronal responses to changes in behaviour, physiology, and environmental stimuli. Building upon this sophisticated yet simple nervous system, C. elegans also possesses a conserved gut which interacts directly with its environment, allowing researchers to study gut and neuronal responses in an integrated way.  

Critically, C. elegans responds to microbial signals and dietary compounds in ways that can predict outcomes in higher organisms, making it a powerful tool for translational research with a gut and cognitive focus. C. elegans also has many characteristics, making it ideal for fast, scalable research. Its size and short life-cycle makes it ideal for conducting high-throughput experiments, across its whole lifespan, in a fraction of the time of other models. Along with this, the ability to genetically manipulate strains to model various genetic diseases and conduct genetic studies, further expands its value. All in all, C. elegans serves a cost-effective whole organism model, exempt from the strict ethical regulations governing vertebrate research, allowing for faster project start-up and broader screening, without compromising scientific integrity. 
 

Can C. elegans Model Gut-Brain Interactions? 

Yes – and it has done so in a multitude of published studies. Research on C. elegans is already revealing how microbes, dietary components and bioactives impact the gut-brain axis. For example, C. elegans has been used to show neuroprotective and ageing benefits of probiotic strains such as Bacillus Subtilis - delaying neurodegeneration in Alzheimer’s disease C. elegans models – and Bacillus Licheniformis – enhancing the longevity of C. elegans through serotonin signalling2,3. These sorts of studies highlight the ability of C. elegans to bring to light potential therapies for existing conditions. Other studies display the impacts that microbial metabolites have on worm behaviour. For example, bacterial metabolites that can synergise with serotonin to influence the serotonin-dependent egg-laying behaviour4.  

C. elegans can also be used to display the neuroprotective effects of various plant extracts highlighting their potential for assessing functional ingredients targeting cognitive health and healthy ageing. For example, C. elegans Alzheimer’s and Parkinson’s models have shown neuroprotective effects when treated with various plant and fruit extracts5,6. The extent of gut-brain axis data that can be gained from C. elegans is broad, encompassing behavioural outcomes, neuronal activity, stress physiology and much more, making it an excellent model for ingredient discovery. 
 

How Can it Speed Up Ingredient Discovery? 

C. elegans is ideal for early-stage high-throughput screening of multiple strains or compounds in parallel, making it a valuable tool for accelerating ingredient discovery. Time-course studies can track effects on gut and cognitive health over hours or days, allowing scientists to identify dose responses, synergistic effects, or even potential negative impacts, early on. This reduces the risk of failure further downstream, where it is more costly, and increases confidence when progressing with lead candidates. By generating meaningful biological data quickly and at scale, C. elegans helps discovery teams move faster from exploration to validation. 

Turning Insight into Action 

If you’re working on nutraceutical products, C. elegans offers a fast, scalable way to generate early-stage gut-brain axis data. Whether you’re at the exploratory or optimisation stage of your product development, technology such as Magnitude Bioscience’s WormGazerTM platforms – for high-throughput screening to in-depth characterisation – offer flexible, data-rich outputs to guide ingredient development. As demand grows for robust, biologically grounded evidence in this space, C. elegans offers an efficient bridge between early discovery and real-world product development. 

References 

  1. Business Wire. Human Microbiome Market Size, Share & Trends Analysis Report, 2024 – 2030. Global press release, 2024. 
  2. Cogliati S, Clementi V, Francisco M, Crespo C, Argañaraz F, Grau R. Bacillus Subtilis Delays Neurodegeneration and Behavioral Impairment in the Alzheimer’s Disease Model Caenorhabditis Elegans. Journal of Alzheimer’s Disease. 2020 Feb 4;73(3):1035–52. 
  3. Mi Ri Park, Oh S, Seung Bae Son, Park DJ, Oh S, Sae Hun Kim, et al. Bacillus licheniformis Isolated from Traditional Korean Food Resources Enhances the Longevity of Caenorhabditis elegans through Serotonin Signaling. Journal of Agricultural and Food Chemistry. 2015 Nov 19;63(47):10227–33. 
  4. Chen YC, Seyedsayamdost MR, Ringstad N. A microbial metabolite synergizes with endogenous serotonin to trigger C. elegans reproductive behavior. Proceedings of the National Academy of Sciences. 2020 Nov 16;117(48):30589–98. 
  5. Kleawyothatis W, Jattujan P, Chumphoochai K, Chalorak P, Sobhon P, Meemon K. Holothuria scabra extracts confer neuroprotective effect in C. elegans model of Alzheimer’s disease by attenuating amyloid-β aggregation and toxicity. Journal of Traditional and Complementary Medicine. 2023 Jan 1;13(1):93–104. 
  6. Zhu F, Wang BC, Qin D, Su X, Yu L, Wu J, et al. Carpesii fructus extract exhibits neuroprotective effects in cellular and Caenorhabditis elegans models of Parkinson’s disease. CNS Neuroscience & Therapeutics. 2023 Oct 31; 
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