Fillip Port

The Enshittificator Digital products and services keep getting worse. In the new report Breaking Free: Pathways to a fair technological future, the Norwegian Consumer Council has delved…

Criminally funny, but also I'm crying inside

Norway comes for the #TechBros

www.forbrukerradet.no/breakingfree

vimeo.com/1168468796?f...

Fungal-derived cellobiose metabolic pathway fuels T cells to bypass intratumoral glucose competition Solid tumors harbor immunosuppressive microenvironments that inhibit tumor-infiltrating lymphocytes (TILs) through the voracious consumption of glucos…

"Nobody will care about your work about sugar metabolism and transporters in Neurospora crassa"

Nobody can predict what can happen with your work.

www.sciencedirect.com/science/arti...

ShineGAL4 FLP-out clones

#Drosophila calling. Delighted to share our new collection of ShineGAL4 drivers for CNS, FB, muscles, enterocytes, oenocytes and MTs made by @vgirard.bsky.social, @sebsorge.bsky.social and colleagues @crick.ac.uk. All at Bloomington @bdsc.bsky.social

@dev-journal.bsky.social
tinyurl.com/4jpw9jd6

NEB publishes often and has contributed greatly to science. So too do several for-profit organizations, but to say that closed doors IP development without full disclosure is contributing to science is silly. A patent is not a research article and intentionally vague in specifics of description...

apparently hot take:

Biology's purpose is not to solve problems but enhance our understanding of the living world.

Biotechnology is the application of biology to solve problems, make products, and enhance the quality of our lives.

These are two very different things.

The Ai for Bio ppl getting upset when someone says the closed doors corporate product R&D is not considered science because it's not publicly disclosed, archived, and indexed in a public database has been interesting to navigate.

Publish or it didnt happen.

This this this this this this this

Individualized mRNA vaccines evoke durable T cell immunity in adjuvant TNBC - Nature In a phase 1 trial, personalized mRNA vaccines tailored to individual tumour mutations in triple-negative breast cancer induced robust, long-lasting T cell responses and improved prognosis.

Individualized mRNA vaccines evoke durable T cell immunity in adjuvant TNBC.
#BioNTech
www.nature.com/articles/s41...

One on left is a black dog and above it the words “Reality”. Below it is “I chased a squirrel” One the right is a black dog and above it says “LinkedIn”. Below it says, Proud to announce that I effectively executed a rapid-response squirrel displacement strategy to mitigate potential yard intrusions. Humbled by the unwavering support of my family and local stakeholders. This experience reinforced the importance of vigilance, ownership, and continuous improvement. Looking forward to scaling this impact in future engagements.

😂

Thanks @michaelboutros.bsky.social and @crisprflydesign.bsky.social for sharing! 🧪🧬✂️🔬🪰
Multiplexed Cas12a editing plasmids here: www.addgene.org/browse/artic...

Header image with the paper title: "Improved in vivo gene knockout with high specificity using multiplexed Cas12a sgRNAs"

Make your gene knockouts more efficient with multiplexed Cas12a sgRNAs. Our new paper is out now, with tools available from @addgene.bsky.social , www.plasmids.eu and @vdrc-flies.bsky.social.

www.nature.com/articles/s41...

#CRISPR #geneediting #Drosophila 🧪🧬✂️🔬🪰

Summary 🧵 below.

Multiple protein structure alignment at scale with FoldMason Protein structure is conserved beyond sequence, making multiple structural alignment (MSTA) essential for analyzing distantly related proteins. Computational prediction methods have vastly extended ou...

FoldMason is out now in @science.org. It generates accurate multiple structure alignments for thousands of protein structures in seconds. Great work by Cameron L. M. Gilchrist and @milot.bsky.social.
📄 www.science.org/doi/10.1126/...
🌐 search.foldseek.com/foldmason
💾 github.com/steineggerla...

Thanks for your kind words, Simon! Still harvesting the fruits of the seeds planted and nurtured in your lab... 🌱🙏

New paper from Narod Kebabci – “A predicted cancer dependency map for paralog pairs” www.biorxiv.org/content/10.6...

Background: The Cancer Dependency Map from @depmap.org is a fantastic resource that characterises genetic dependencies at genome-wide scale across ~1,000 cancer cell lines. 1/9

This work represents a major team effort, with much of it driven by fantastic undergraduates doing their master thesis, rotations, or pre-university gap year in the lab. Huge thanks to everyone involved! I'm very happy about what we accomplished together.

Part of figure 6 showing the results of a systematic comparison of mutagenesis with Cas12a sgRNA arrays to two currently used Cas9 sgRNA libraries. in both cases multiplexed Cas12a editing outperformed current technology and identified several phenotypes missed by established technology.

So multiplexed Cas12a is safe and specific, but does it actually improve knockout efficiency? Direct comparisons with two established Cas9 libraries show superior performance, uncovering phenotypes that existing approaches miss.

Part of figure 5 showing that Cas12a activity is only detected on chromosome arms with sgRNA arrays targeting genes located on this arm and not elsewhere.

The results were very reassuring: >99% of sgRNA arrays showed on-target activity, while we detected no reproducible off-target cutting on the chromosome arms we screened.

And what about off-target activity you ask? Well, this has so far been difficult to assess in flies due to limited methods. So one of my favorite parts of this paper: we developed an assay to visualize DNA cutting with thousands of sgRNAs over entire chromosome arms.

Part of figure 4 that shows that targeting uncharacterised genes with Cas12a sgRNA arrays does not recapitulate phenotypes known to arise from disruption of neighboring genes (with rare exceptions).

Another potential problem: proximity effects, where cutting one gene also deletes neighbors or entire chromosome arms. Testing genes adjacent to characterized loci, we found minimal evidence of such effects in Drosophila (though rare cases do occur).

Figure 3 showing the number of apoptotic cells in the wing disc epithelium after clustered or dispersed CRISPR cutting. While clustered cuts are moderately toxic, cuts on different chromosomes are highly detrimental.

As expected, DNA cutting causes an increase in cell death, which is moderate when cut sites are clustered, but excessive when they are distributed over different chromosomes (which is likely to give rise to genomic rearrangements).

Mutagenesis through CRISPR nucleases works by creating DNA double-strand breaks, which can cause various side effects, so first we assessed whether causing multiple breaks in close proximity is well tolerated in flies.

These resources are publicly available: fly lines from VDRC, plasmids from Addgene and EPR.

shop.vbc.ac.at/vdrc_store/v...

www.addgene.org/browse/artic...

www.plasmids.eu

Part of Figure 2 showing the different tools we build for multiplexed Cas12a mutagenesis in flies.

We systematically tested Cas12a mutagenesis with 4 sgRNAs per gene in Drosophila. This included building a modular toolkit: sgRNA arrays for 800+ genes, optimized Cas12a transgenes, and activity reporters to map and measure Cas12a activity in vivo.

Multiplexing sgRNAs addresses these issues through redundancy and synergism. While Cas9 arrays with more than 2 sgRNAs are difficult to construct, arrays with 4 Cas12a sgRNAs are compact enough to be synthesized as a single oligonucleotide. ➡️ Easy cloning at scale.

a man in a superhero costume is holding a knife in front of a sign that says nickelodeon Alt: Gif of a man in a superhero costume who is trying - and failing - to cut through a red tape with scissors.

CRISPR gene editing is the most common way to test gene function, but knock-out efficiency is typically limited by silent mutations, inactive sgRNAs and inaccessible target sites.

Header image with the paper title: "Improved in vivo gene knockout with high specificity using multiplexed Cas12a sgRNAs"

Make your gene knockouts more efficient with multiplexed Cas12a sgRNAs. Our new paper is out now, with tools available from @addgene.bsky.social , www.plasmids.eu and @vdrc-flies.bsky.social.

www.nature.com/articles/s41...

#CRISPR #geneediting #Drosophila 🧪🧬✂️🔬🪰

Summary 🧵 below.

This is such an important point and here in Europe we should be building the skills and connections now to make sure that the truth continues to matter and powerful people can be held to account.
The alternative is going down and down the spiral of democratic disenchantment and erosion…

#LivingArchitectures
We put cells and cytoskeleton filaments on the architecture of the musée d'Orsay.
www.musee-orsay.fr/fr/agenda/ev...
Scientists of the #CytoMorphoLab adapted their protocols to illustrate the questions that keep them awake at night.
-> Two shows on the 24th and 25th of January.

#LivingArchitectures

Congratulations @manuelthery.bsky.social @lblanchoin.bsky.social and all Scientists of the #CytoMorphoLab for their poetic vision of the microscopic level.

😵