Lydia Mapstone, PhD

If you're working with one of the more "unique" species and struggling to find antibodies that are validated in said species, you don't have to go through the struggle alone. 🤝 Just yesterday a researcher approached me saying they were struggling to find antibodies for ~10 targets - their species of interest - drosophila (that's a fruit fly for any none scientists like me out there). 🪰 << not a scientifically accurate emoji. Within less than 24 hours, I'd received their list, sent it to our amazing R&D team and received back an analysis of what we have on our catalogue and if it's likely to cross react with drosophila. 💡 A painful task for the researcher, made simple by our brilliant scientists. 👏🏻 Pair that with our product guarantee if they don't happen to work & the ability to try small tester sizes first and you're laughing. Find me a company that works this hard to help it's customers... I'll wait 😍 Ask your Proteintech Group rep to do the same for you today! #ELISA #IF #antibodies #WesternBlot #FlowCytometry

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With so many badass publications now featuring Oxford Nanopore Technologies, the teams are now assembling monthly blogs - read on for a digest of COOL OMICS https://lnkd.in/eFJTJ-em My pick of the pick: Real-time genomic characterisation of paediatric acute leukaemia using adaptive sampling (bioRxiv) -Peripheral blood or bone marrow from 54 paediatric acute leukaemia cases with diverse genomic subtypes were analysed. -Adaptive sampling was used to enrich 59 genes commonly involved in translocations/fusions in B-cell acute lymphoblastic leukaemia (B-ALL) and acute myeloid leukaemia (AML). -Oxford Nanopore sequencing provided all genomic information currently offered by traditional diagnostic testing (karyotype, FISH, and occasional microarray) for paediatric acute leukaemia, but was also able to characterise aneuploidy and structural variants in challenging repetitive regions. -There was no loss in sensitivity or throughput between freshly collected and cryopreserved samples, whereas karyotype and FISH are reliant on high-quality viable cells. -The researchers suggested that nanopore sequencing could be a low-cost future alternative to current diagnostic tools, increasing accessibility to LMICs.

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I am incredibly proud to announce that we have been awarded a £1.6M project from Innovate UK’s Biomedical Catalyst 2023 Round 2: Industry-led R&D 🙌 This application took a tremendous amount of effort, including working well into the early hours of many mornings to perfect the initial submission and cancelling leave over Christmas to prepare for the interview stage. Innovate UK grants (rightly!) require significant work; the application is scrutinised by five experienced assessors from various areas across Life Sciences. The next-stage interview is then attended by up to ten other people, with our panel including professionals from the NHS, academia, and CDMOs, among others. With a pot of £17.8M, and average project cost at £415,191, only 30 of the 358 applications could be funded 💰 . It is therefore truly gratifying to have so many experts agree that the cause we are developing solutions for is important and worthy of this substantial investment ✊ We do not take this funding lightly and will work tirelessly to ensure the success of our exciting project. Time to get cracking! https://lnkd.in/ev58aTt8 #biomedicalcatalyst #healthcare #infantmicrobiome #microbiome #grantfunding #grants #investment #innovateuk #biotech

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"Science isn't finished until it's communicated." — Sir Mark Walport We constantly ask ourselves, how can we meet people where they are while translating the complexities of the microbiome in a beautiful and engaging way? It definitely takes an ecosystem. This week at Seed Health, we launched a new iteration of our series Bathroom Classroom on Instagram Reels. The 6-episode series looks at efficient ways to bio-hack your bowels with things like the mechanics of chewing food, the implementation of toilet stools, and (of course) #probiotics.¹ Completing this course gives our community an opportunity to unlock a free DPMD (Defecation Postural Modification Device). A big thank you to the creators (writers, designers, motion graphics and video editors, and scientists) who brought these videos to life: Sean Horner, Mimi Nguyen, Kathryn LaBarbera, Elaina Martino, Spencer Elias, Jordie Nazzicone, MPH, ND, Stephen Skolnick, Jennie O'Grady, Bryan Merrill, Erin A. Miller. • ¹ Poop is one of the most important (and visible) biomarkers of your gut health but for many people, it's not an easy experience. In America alone, nearly 70 million people are quietly living with #digestivehealth issues (nearly 50 million experience chronic constipation). Almost 15% of the population is suffering from Irritable Bowel Syndrome (#IBS) in addition to other chronic conditions like #Crohn's, #UlcerativeColitis, and #GERD. For us, the #microbiome offers a new lens for understanding these chronic issues.

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🧬 Exciting news out of the UK as the Medical Research Council & THE BIOTECHNOLOGY AND BIOLOGICAL SCIENCES RESEARCH COUNCIL (BBSRC) have provided £28.5 million in funding to establish the Human Functional Genomics Initiative programme. 🧑‍🔬Jonathan Mill has been appointed as Director to lead the #initiative that aims to advance understanding of how genomic variation influences human physiology and how it changes over time and in disease. 📚𝑭𝒖𝒏𝒅𝒊𝒏𝒈 𝒃𝒓𝒆𝒂𝒌𝒅𝒐𝒘𝒏; - £7 million that will be used to establish a functional genomics screening lab. The lab will perform arrayed #CRISPR genetic screening for HFGI researchers investigating noncancerous diseases including ones affecting the immune, cardiovascular, nervous, and respiratory systems. - £16.9 million will be used to fund 𝐟𝐮𝐧𝐜𝐭𝐢𝐨𝐧𝐚𝐥 𝐠𝐞𝐧𝐨𝐦𝐢𝐜𝐬 research clusters. - £4.6 million will be provided by the 𝐔𝐊𝐑𝐈 councils to support data coordination and networking, as well as collaboration among the program's research clusters and external partners. Good news for #genomic developments across the UK. For more information, take a read of the article below 👇

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It's crucial to utilise both sequence and structure information for protein representation as they present different resolutions of the same underlying data. It's great to see recent increase in efforts to this to improve AI/ML models for protein design and engineering. The authors in SSEmb below present a method for this. https://lnkd.in/eznqYkUJ

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🚀 Interesting new multimodal foundation model for chemistry from March. Why does it matter and what does SPMM do? 📌 It combines information from 50,000,000 SMILES and 53 chemical properties of the SMILES 📌 It can predict the chemical properties given a SMILES, as well as generate a SMILE given chemical properties

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It was a real thrill for me to see so many structural biology talks at ELRIG UK Protein Sciences, especially the Keynote by Cheryl Arrowsmith from The Structural Genomics Consortium (SGC), who discussed using #AI to tackle undruggable targets with small molecules, finding binders despite negative AlphaFold predictions 💪 This is an area I’ve always believed AI would tackle first, but it has been lacking so far, and SGC has recognised this need. Even more exciting is the launch of CACHE (https://lnkd.in/eacnrs3t), a small molecule equivalent to CASP (where AlphaFold proved their mettle), but this time focused on ligand prediction. CACHE has issued an open call for protein targets and people who can make them 📣 A quote that resonated with my friends and colleagues at #ELRIG was: "Structural biologists make the best proteins, it's true." As Isogenica's senior protein engineer, I wholeheartedly agree. 😉 During the Q&A, a question also arose about strategies for "rescuing protein." The best approaches suggested were using multiple constructs, exploring different expression systems, and emphasizing the use of ligands. 🔗 Ligands typically stabilise the protein and reduce how much the protein moves (the free energy) making it more amenable to crystalllisation. While natural cofactors or partners commonly serve as ligands, VHHs (also known as "nanobodies") can also fulfill this role and are commonly known as "crystallisation chaperones", particularly for challenging targets such as membrane proteins. If using VHHs in this way is something you would like to explore with Isogenica , please get in touch as I would be delighted to embark on another structural biology challenge! 🤩 The Protein Society #ELRIG2024 #StructuralBiology #ProteinScience #AlphaFold #LigandPrediction #CACHEChallenge #UndruggableTargets #Nanobodies #MachineLearning #ArtificialIntelligence

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Antibody structure prediction tool ABodyBuilder3. Another nice piece of work from Prof Charlotte Deane's team. I particularly liked the use of minimisation in explicit water and uncertainty estimation. Title: ABodyBuilder3: improved and scalable antibody structure predictions Abstract: In this article, we introduce ABodyBuilder3, an improved and scalable antibody structure prediction model based on ABodyBuilder2. We achieve a new state-of-the-art accuracy in the modelling of CDR loops by leveraging language model embeddings, and show how predicted structures can be further improved through careful relaxation strategies. Finally, we incorporate a predicted Local Distance Difference Test into the model output to allow for a more accurate estimation of uncertainties. https://lnkd.in/enuu_2BG

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Yet another diffusion based protein structure prediction work. It's great to see many tools now available for protein engineering. What a fantastic time to be working in this area! Article: De novo protein design with a denoising diffusion network independent of pretrained structure prediction models Abstract: The recent success of RFdiffusion, a method for protein structure design with a denoising diffusion probabilistic model, has relied on fine-tuning the RoseTTAFold structure prediction network for protein backbone denoising. Here, we introduce SCUBA-diffusion (SCUBA-D), a protein backbone denoising diffusion probabilistic model freshly trained by considering co-diffusion of sequence representation to enhance model regularization and adversarial losses to minimize data-out-of-distribution errors. While matching the performance of the pretrained RoseTTAFold-based RFdiffusion in generating experimentally realizable protein structures, SCUBA-D readily generates protein structures with not-yet-observed overall folds that are different from those predictable with RoseTTAFold. The accuracy of SCUBA-D was confirmed by the X-ray structures of 16 designed proteins and a protein complex, and by experiments validating designed heme-binding proteins and Ras-binding proteins. Our work shows that deep generative models of images or texts can be fruitfully extended to complex physical objects like protein structures by addressing outstanding issues such as the data-out-of-distribution errors. https://lnkd.in/eNYvV8GR

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A very interesting piece from The Scientist discussing how embedding cryptic DNA code in synthetic molecules could help lower biosecurity threats 💡 What a fascinating era of science we live in! Checkout the full article below 👇🏽 #syntheticdna #biosecurity

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Science, Sep 2024 Title: "The revolution in high-throughput proteomics and AI" Interesting read describing how UK Biobank’s studies combining Olink Proteomics, #genetic, health, and lifestyle information uncover new insights about the underpinnings of disease, the #aging process, and the potential ability to forecast an individual’s health trajectory. The authors conclude that: "Not to be missed at this juncture is that we indeed are seeing an exciting development of the proteomics field and AI, which will continue to build and ultimately find its place in routine medical care." #Olink #Proteomics #AI

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Lots of things to write about from last week, which culminated on Friday with the launch of the National Alternative Protein Innovation Centre (NAPIC) in Leeds. But first, this week the Department for Science, Innovation and Technology released an analysis of the thoughts of 3,000 UK adults on engineering biology. Which is good! We need a baseline - see where we are now with things. The link to the report is here which has an exec summary that I won't repeat: https://lnkd.in/eVBpepph But a couple of other things I pulled out from the report. Again, setting that baseline, the folks were asked a number of questions re what is important to them, how they deal with new tech etc. And really UK people? 43% of you have immigration as in the top three issues facing the country? above education; climate; even above health! So - this is where we are starting from. The report also mentions that the people surveyed were those that had already signed up to be "surveyed" for various things. Which is fine, but also perhaps self-selects in some way. Weirdly, the youngest (18-24) were the ones that say they have heard about EB, and could at least give a partial explanation of it, but pretty interestingly this same subgroup also were the least likely to say that EB was an overall positive thing for society (still at very lovely 70%), and had the highest proportion saying it was a negative thing (13% vs 5 or 6% for other age ranges). What does this mean? The more you know the less good you think EB can be? OR - the more you THINK you know, the less good you think EB will be? The respondents weren't asked that they THINK EB is, just if they think they know what it is - I think those answers would have been interesting. It would also have been interesting to know where they get their info from - the anti-vaxxers on YouTube with a cult-like following, reputable sources? Facebook? BUT overall the report is really positive, with the vast majority of people knowing something of EB, and thinking it will impact positively across food, agri, chemicals, materials and health. One final point that struck me - which brings me back to the National Alternative Protein Innovation Centre (NAPIC) launch - people place a higher emphasis on the environmentally friendliness of their low carbon fuels, chemicals and recycled waste (the things we expect these days to be trying to be "greener"), than they do for food. And I wonder if this if because "we" don't actually know the environmentally (un)friendliness of our food? ..and so to the wonderfully terrifying keynote from Tim Benton - telling us things that some of us have heard before..but easily forget. And some things I hadn't really heard/considered before. Food is not just food. politics - war - nationalism - climate - it is all connected with this wonderful ball we ALL call home🌍 #syntheticbiology #engineeringbiology #altprotein

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Dr Jen Vanderhoven is bar far one of the most passionate and driven people I know. I honestly believe she is single handedly making the most Impact for #ukbiotech and #bio-based materials. Making the BBIA the fastest growing most modern trade association trying to make a #realdifference. If you want to be apart of the #bioeconomy and #biorevolution get in touch. Keir Starmer

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Whole plasmid sequencing using short read from Illumina and long reads from Oxford Nanopore Technologies has the potential to streamline the quality control of plasmids used in #biotechnology and #lifescience. Casey-Tyler Berezin, PhD and Sarah Hernandez led an effort to evaluate the reproducibility of plasmid sequencing workflows. Some commonly used plasmids are surprisingly challenging to sequence, even when using a hybrid assembly strategy that combines long and short reads. Read the preprint at https://lnkd.in/e6VireeS Contact me if you need help verifying your plasmids. #lablife #synbio #syntheticbiology #reproducibility #biology #molecularbiology

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After the first protein structures were solved (myoglobin, haemoglobin) then the earliest genomes were sequenced. (bacteria, yeast) we have arrived through DNA sequencing and 3D structure prediction (Alphafold as described here) at a great toolkit for tackling the mechanics of the cell. Now the (holistic) challenge is to put it all together especially to grasp the functions of the manifold “non coding” regions of DNA. As this is acheived in the coming years, we will be enabled to journey back into deep time to appreciate the foundations of life in a manner that we simply conjecture at present. What a time for life scientists themselves to be alive! #proteins #structure #function #evolution #Alphafold

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Are the 3 R's enough? The 3 R's for animal research —refinement, reduction, and replacement of experiments with animals— are foundational for ethical animal research, minimizing harm and animal use. At ProtoQSAR, we work to push these principles further by developing computational models that help reduce reliance on animal testing, fostering innovation and ethical progress. Rebecca Critser and Paul Locke propose expanding this framework with the "3 V's": · scientific validity (models should reflect human biology) · species validity (using the right species) · societal validity (aligning with ethical standards). More details here at the AMA Journals of Ethics: https://lnkd.in/dyGgU--Y

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Some thing I have worked on Characterization of the mode of action of eCry1Gb.1Ig, a fall armyworm  (Spodoptera frugiperda) active protein, with a novel site of action

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