Claus Crone Fuglsang

How is it possible that a small team purified over 200 full-length membrane proteins in their native lipid environment in only 2 years? For decades, membrane protein purification was unpredictable, slow, and resource-intensive. Every new target meant days, weeks, months - sometimes even years - of trial and error with no guarantee of success. This automated workflow described in our recent preprint (enabled by NativeMP™) changes this fundamentally: • 20+ hours of manual work → ~90 minutes • 1 screen = 16 copolymers • 1 plate = 6 screens in parallel (96 wells total) • Direct read-out of which copolymer + buffer stabilizes your protein best On a standard KingFisher system this means 6 complete conditions in ~90 minutes. Scaled across a workday, that is dozens of conditions or multiple proteins in the time it once took to test just one. The workflow was applied to GPCRs, transporters, ion channels, claudins. In the case of the P2X4 receptor, screening across different copolymer conditions delivered cryo-EM samples at 2.9 Å resolution. The “secret recipes” of membrane protein purification are no longer hidden. ✨ Now it is your time to shine. Full preprint in the comments. ————————— ♻️ Repost if you found this valuable! 📩 Follow me for discussions on biotech, membrane proteins, and lab innovations.  

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Today AstraZeneca announced a major investment of $50 billion by 2030 for manufacturing and R&D across the United States. The cornerstone of this investment is the Company’s largest single investment in a facility to date – a proposed new, state-of-the-art facility in Virginia that will produce drug substance for our innovative weight management and metabolic portfolio. This underscores our focus on the underlying causes of cardiometabolic disease – as we move away from reactively treating individual conditions to treatments that can address the complex, interconnected needs patients face every day.     As a global leader in CVRM, with one of the broadest, deepest, pipelines in the industry, we are uniquely positioned to improve outcomes for people living with obesity, overweight and diabetes. This is such an important investment in our future and is integral to delivering AstraZeneca’s 2030 Ambition and offering new treatments to the nearly 130 million Americans living with a chronic disease.     #AZUS #WhatScienceCanDo #Innovation #LifeSciences #R&D #Manufacturing 

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Do linker “rules” really exist - or are they purification artifacts? My recent linker posts have received a lot of attention and have triggered great discussions in the comments (big thanks to all contributors 🙏). I found another controversial subject: linker length and how it impacts the oligo- meric state of the products! The dogma for designing protein fusions with (mainly G4S) linkers still is: 1️⃣ Long linkers (15–25 aa) yield monomers 2️⃣ Medium linkers (6–15 aa) yield dimers 3️⃣ Short linkers (1–5 aa) yield trimers or even higher-order oligomers But the study by Long et al. (2018, JBC) showed something striking which seems to have gone unnoticed (at least I couldn´t find any paper following up on this). 🚨These “rules” held true only after Ni–NTA (IMAC) purification. When the same scFv constructs were purified with Protein L, the picture shifted completely: ⚠️ More heterogeneous mixtures ⚠️ Higher-order oligomers across multiple linker lengths ⚠️ Gradual transitions, no sharp cutoffs between mono-/di-/trimers The likely explanation? Multivalency of His-tagged oligomers. In IMAC, multimers bind more tightly, biasing the sample toward monomers and dimers. Protein L, by contrast, releases everything at low pH. What does that mean? 👉 Ni-NTA does not just purify, it selects 👉 Yields shift and recoveries depend on the purification method. Or as the authors conclude in the discussion: ❝Therefore, we must reconsider linker length rules in light of how the molecules have been purified.❞ Have you obeserved similar purification artifacts❓   I am Sebastian, founder of PAIA Biotech, posting regularly about developability of biologics and technologies for assessing molecules in early discovery. #developability #antibodydiscovery #leadoptimization #PAIA

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Being fast on your own - or getting ahead together? In the biotech sector, there is only one answer: collaboration is the key. Without strong partnerships, innovation in our field would hardly be possible. Why? ➡️ Risk sharing Biotech development is complex and expensive. Partnerships help to share investments and risks - a decisive factor for success. ➡️ Speed A large partner not only brings financial resources, but also infrastructure, know-how and market presence. This speeds up processes enormously. ➡️ Technology transfer Large pharmaceutical companies look specifically for innovative technologies. Start-ups and specialized companies bring these to the table - a win-win situation. How do we choose the right partners? Strategically. Targeted. In the long term. But why is the whole topic so relevant? Biotech companies, especially in Europe, are often faced with the challenge of turning their research into scalable products. This is almost impossible without strong partnerships. In an environment where other countries are creating better funding conditions, strategic collaboration becomes all the more important.

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Today we proudly announced the formation of Kalexo Bio, a portfolio company of Aditum Bio Fund 3, which will develop a new cardiovascular drug in collaboration with Mabwell Biosciences. This novel, dual target siRNA therapy for lipid management will be developed in patients with dyslipidemia, for the prevention of high-risk atherosclerotic cardiovascular disease (ASCVD). This therapy combines two genetically validated targets which are major drivers of cardiovascular disease: Lp(a) and PCSK9.  Over 400 million people globally suffer from atherosclerotic cardiovascular disease, which remains a leading cause of death. We look forward to rapidly moving this therapy into the clinic, and to patients in need. Congratulations to the Aditum Bio team for getting this deal over the finish line.  View the press release here: https://lnkd.in/gXTG3Ktt

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The future of biomanufacturing won’t be centralized. (And our new collaboration with Matica Biotechnology shows how) Cirsium’s plant-based AAV platform was designed for speed, flexibility, and global scalability. But upstream breakthroughs only matter if they integrate with downstream expertise. That’s where Matica Bio comes in. As an early partner in our hub-and-spoke model, they bring world-class expertise in analytics and purification; complementing our plant-based production. Together, we will: - Scale AAV production without relying on mega-facilities - Shorten timelines from lab to clinic - Expand patient access by lowering manufacturing barriers - Significantly reduce the cost per dose for gene therapies It’s a glimpse of how the industry will operate in the future: decentralized, modular, and built on collaboration. Proud to be shaping that future with Paul Kim and the Matica Bio team. Onward. Full press release can be accessed here: https://lnkd.in/ggXJYx_n

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