Setting up and optimising automation for lab tasks can sometimes seem like more hard work than it’s worth. What if you could ‘trial’ the method in silico and then move to the actual instrumentation for final checks? Ross will be describing a platform that does exactly that!

Making automation more accessible can have numerous advantages, it relieves scientists of repetitive lab tasks, can reduce the amount and exposure to hazardous regents and maybe a good starting point for streamlining consumable use.

The platform also uses the ‘design of experiments’ approach, systemically structuring an experimental plan which can allow efficient method development too. All contributing to reducing reagents, consumables and time in the laboratory which in turn reduce cost and improve sustainability.

Ross will be talking on Wednesday 22nd October in Auditorium 3 track ‘Sustainable drug development: how can we mitigate environmental impact’ at ELRIG’s Drug Discovery 2025.

When knowing the right target really mattered – the story of a COVID-19 oral antiviral.

In March 2020 it became clear the COVID-10 pandemic was going to affect us all, whether our health or our work. In drug discovery, identifying the right target is key, Pfizer’s previous work on SARS had focused on the main protease involved in the cleavage of the polyproteins involved in viral replication, which was also present in SARS-CoV-2 and the binding site was well conserved. This earlier work had been successful in identifying nanomolar inhibitors of the SARS main protease.

There was good evidence to support the target protease for both safety and efficacy, but the lead candidates were suitable for intravenous administration not oral. Dr Dafydd Owen said that “What do we do next if this works?” was the question he asked his team each day.

Dr Dafydd Owen is giving the Plenary Keynote Presentation on 22nd October at 09:05 at ELRIG’s Drug Discovery 2025 conference.

Cryo-electron tomography (cryoET) is an imaging technique that captures 3-dimentional structures within cells and tissues, resolving proteins and organelles and how they interact. The ongoing molecular processes captured in these data can aid understanding of disease mechanisms, progression and ultimately assist in developing diagnostics and therapeutics.

Unfixed cells or tissue biopsies are prepared and cryo-preserved, as the name suggests, at incredibly cold temperatures (approx. -170°C) where the water in the sample is frozen very rapidly, ‘vitrifying’ it, and preventing ice crystals from forming that would otherwise damage delicate cellular structure. Cryo-preserved tissues are then thinned to (70-120nm) with a diamond knife and gold eyelash or focussed ion-beam and placed onto a 3 mm copper grid before cryoET datasets are collected.

Maddie Gilbert describes the challenges of these methods and the inspiration that she got when the images revealed β-amyloid plaques and tau amyloid pathology within postmortem Alzheimer’s disease donor brain. The resolution afforded by cryoET combined with downstream processing enabled the polypeptide backbone and the β-sheet confirmation of the amyloid protein to be seen within donor tissues.

Maddie will be presenting her work during the scientific track ‘What’s new in Protein Sciences in collaboration with The Protein Society’ on Tuesday 21st October at ELRIG’s Drug Discovery 2025.

Cells change shape, both the process and the resulting shape can tell us about the cell and it’s capabilities.

We are very used to seeing static images of cells, even if those images are 3D yet we often over-look the fact that cells are dynamic, changing morphology all the time, obvious examples are muscle cells for movement and brain neurons for memory.

Shape change also happens in a ‘dysregulated’ way, causing disease. Chris’s group are especially interested in the changes that occur when cells become first cancerous and second metastatic

Imaging techniques now enable us to examine cells live and in environments that mimic physiologically relevant environments, generating significant amounts of data for interpretation. AI and machine learning can assist with the data interpretation in a similar way to analysing a sport’s person swing or kick on the court or field. If we can predict from early changes a cell’s future e.g. a primary cancer cell moving toward becoming metastatic then this can help stop the shape-change an prevent disease progression.

Chris Bakal, from the Institute of Cancer Research and Sentinal4D will be presenting on ‘4D morphodynamics to power AI-driven drug discovery. Learning from shape’ in scientific track ‘Use of novel technologies to enable drug discovery and drug repurposing in collaboration with the British Pharmacological Society’ on Wednesday 22nd October at ELRIG’s Drug Discovery 2025.

Let AI find patterns. Let models explain them. Machine learning can highlight what we might miss, but not why it matters.

Mechanistic models based on human biology help us ask better questions earlier, integrating in vitro systems with transparent, mechanistic models helps reduce animal use while improving scientific relevance, traceability, and the quality of decisions.

To improve how we develop therapies, we need to better reflect the diversity of human populations. Mechanistic models make it possible to simulate physiological differences across sexes, ages, life stages, and disease states. Women’s health is one example where this matters deeply, from pregnancy to hormonal transitions, but the same applies across many underrepresented groups. Modeling tools can help us close persistent data gaps, improving safety, efficacy, and trust.

Marco Siccardi will be speaking on 21st October, in track ‘In vitro and in silico models for sustainable drug discovery’ at 11.10am about ESQ’s work in building open-source models initially for metabolism (ADME) and pharmacology and the considerations and advantages this brings for drug discovery. ESQ has chosen to produce an open-source platform approach as it makes modeling transparent, reusable, and collaborative.

Cereblon is a component of an E3 ubiquitin ligase complex – it’s role is to bind a substrate protein and ‘hold’ it for ubiquitination, which marks the protein for subsequent degradation. Certain chemical probes called ‘molecular glues’ are able to bind a pocket on the surface of cereblon which ‘recruit’ new target substrates, resulting in their degradation.

The range of proteins that can be recruited by cereblon is determined by its surface conformation, however Lyn Jones and the team at the Dana-Farber Cancer Institute asked the question ‘What is the most diverse list of targets we can imagine?’ Cereblon, to date, has only been modulated by non-covalent probes, so they developed new chemistry to modify surface residues and therefore change the binding interface.

They validated this approach by modifying a surface histidine residue on cereblon which in turn triggers the recruitment and degradation of NTAQ1, a protein previously deemed ‘undruggable’. The molecular glue degrader will help studies of the role of NTAQ1 in DNA damage repair, which may have therapeutic applications in cancer.

Lyn will be presenting ‘Synthetic manipulation of the cereblon surface using sulfonyl exchange chemical biology’ on Wednesday 22nd October in the scientific track ‘Chemistry and innovations in drug discovery in collaboration with the Royal Society of Chemistry, with support from the RSC Medicinal Chemistry Journal’ at ELRIG’s Drug Discovery 2025.

UK Biobank, the world’s most comprehensive biomedical dataset, has been collecting vast amount of health information from its 500,000 volunteers for almost two decades.

The resource holds a wide variety of data types, including physical measurements and healthcare records through to whole-genome sequences, proteomics and other biomarker data. This provides a comprehensive resource for researchers around the world working to improve public health, including drug targets and their likely safety and efficacy.

UK Biobank is continuing to build on its world-leading resource by regularly adding new and updated data. The team recently celebrated the completion of the world’s largest whole-body imaging project, with scans from 100,000 volunteers expected to be made available to researchers later this year.

UK Biobank’s lead data analyst Lucy Burkitt-Gray will talk about ‘Leveraging the UK Biobank resource for accelerated drug discovery’ on Wednesday 22nd October in scientific track ‘Making the impossible possible: Using artificial intelligence to tackle challenges in drug discovery’ at ELRIG’s Drug Discovery 2025

Mass spectrometry is not usually considered a phenotypic screening technique yet with increased throughput, automated data acquisition and improved data analysis platforms, it deserves a second look.

Leonie presents a proof-of-concept study where the group established a novel MALDI-TOF MS fingerprinting strategy that effectively distinguished macrophage phenotypes and identified phenotype-specific biomarkers. The screening capacity was tested by treating human induced pluripotent stem cell-derived macrophages with a compound library which included known anti-inflammatory compounds.

Comparison with an established cytokine-profiling immunoassay demonstrated good agreement and highlighted potent anti-inflammatory compounds. In addition to good agreement, the utilised proteomics platform enabled unique insights into molecular pathway engagement.

Leonie Mueller from the University of Newcastle, will be presenting her talk ‘MALDI-TOF mass spectrometry and proteomics as phenotypic screening tools for anti-inflammatory drugs’ in the scientific track ‘Chemical biology and ‘omics for small molecules – technologies, developments and learnings’ on Tuesday 21st October at ELRIG’s Drug Discovery 2025.

While much of modern drug development applies to proteins, many critical disease mechanisms remain undruggable at the protein level. Targeting RNA offers an alternative way to intervene, upstream in the disease pathway.

RevoNA Bio focuses on the structural architecture of RNA to discover small molecules that modulate its function. By systematically exploring structured RNA elements across disease-relevant transcripts, RevoNA Bio’s platform can reveal small molecule drugs that disrupt oncogenic processes for therapeutic benefit.

Reece Gardner, Chemistry and Biophysics Lead at RevoNA Bio, will be discussing the approach and a case study in his talk ’Discovery of small molecule modulators of oncogenic RNA targets’ on Wednesday 22nd October in track ‘Accelerating delivery of patient benefit for all cancer patients, in collaboration with Cancer Research Horizons’ at ELRIG’s Drug Discovery 2025.

Transferring assays is a regular occurrence between labs, whether within the same parent company or externally to a contract research laboratory or service provider. An investment in time and effort to make method transfer more reliable and less prone to problems is worth it for many labs.

Gareth is presenting a case study where a biochemical assay in 384 well format was miniaturised to 1536 format, saving time, reagents and plastic. The automation protocol was designed on a web-based platform so the method could run on two different systems and be transferred to a second site.

Using the web-based platform to prepare the automation script gave lab scientists confidence in using the automation instrumentation and super-users reassurance that the equipment was being used appropriately and effectively.

Gareth is speaking on 21st October in track ‘From sample to data to insight – how robotics and automation enables the science of discovery’ at Drug Discovery 2025.

Working backwards from a clinical effect might seem an odd approach, but in the case of the deubiquitinase Ubiquitin Specific Protease USP30, this has been the challenge for Darragh O’Brien’s research. USP30 inhibitors had recently advanced to clinic trials, but the mechanism of action (MoA) was still not yet fully established.

At the outset of the study, structural information for USP30 was not available, making it difficult to look at the conformation of the USP30 inhibitor binding pocket. Darragh used a structural proteomics approach to characterise the binding site of different types of USP30 inhibitors on the protein, as traditional crystallography had not yet been successful. Activity-Based Protein Profiling Mass Spectrometry (ABPP-MS), Hydrogen-Deuterium eXchange Mass Spectrometry (HDX-MS) and other supporting biophysical techniques coupled with enzyme kinetics enabled the development of a structural model which showcased the potency, activity, and selectivity of different USP30 inhibitor classes.

The data obtained from the highly integrative approach resulted in a proposed MoA for non-covalent USP30 inhibition. The work has since been extended to include covalent inhibitors, and has been confirmed by others in the field, paving the way for the development of next-generation inhibitors of USP30 targeting neurodegenerative disease and mitophagy-related disorders.

Darragh O’Brien is a Researcher in Neurodegenerative Disease and Head of Structural and Mechanistic Proteomics at the Centre for Medicines Discovery, University of Oxford. His talk ‘Targeting mitochondrial dysfunction in neurodegenerative disease – The advent of potent and selective USP30 inhibitors’ will be presented on Wednesday 22nd October at ELRIG’s Drug Discovery 2025, in the scientific track ‘From bench to brain: Hit-finding approaches in neurodegenerative disease therapeutics in collaboration with Alzheimer’s Research UK’.