Fillip Port
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crisprflydesign.bsky.social
Fillip Port
@crisprflydesign.bsky.social
2.3K followers 900 following 270 posts
Scientist at the German Cancer Reseach Center in Heidelberg. We develop genome engineering tools for functional genomics. #CRISPR #Drosophila #openscience
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crisprflydesign.bsky.social
🤯This is wow! Molecular mechanism of mRNA export. by @juliusbrennecke.bsky.social @plaschkalab.bsky.social

www.nature.com/articles/s41...
Illustration of the molecular mechanism controlling mRNA export.
November 6, 2025 at 5:20 PM
crisprflydesign.bsky.social
High levels of Cas9 are toxic in sensory neurons. Reducing Cas9 levels with uORFs avoids toxicity and is compatible with efficient editing. From @thompsonpeerlab.bsky.social. Fly lines @vdrc-flies.bsky.social

#CRISPR #Drosophila

www.biorxiv.org/content/10.1...
Figure from the preprint showing sensory neuron morphology with different levels of Cas9 expression.
October 4, 2025 at 9:10 PM
crisprflydesign.bsky.social
Hey @nature.com What's up with your share buttons? Can we please also get 🦋 and 🦣 options to not exclusively promote the network of the guy who has done more than most to harm US science?
July 16, 2025 at 5:46 PM
crisprflydesign.bsky.social
Some PIs will stop at nothing to motivate their lab members. 🧪
Graffiti at the end of an underpass in Heidelberg saying 'LAB!'.
July 12, 2025 at 11:41 AM
crisprflydesign.bsky.social
Journal spam often gets it wrong, but I do agree that "{title}" is a particularly significant study of mine. 😂🙄
Email invitation to a spam journal based on a previous study titled "{title}"
June 23, 2025 at 3:04 PM
crisprflydesign.bsky.social
Proud parenting moment 🎸
F1 playing guitar at a school band gig.
June 21, 2025 at 8:12 PM
crisprflydesign.bsky.social
Oh nice. We were there just a few days ago. Did a nice hike up to Lac Bleu between Haudères and Arolla. Nice on a hot day, as most is in the forest.
Picture of Lac Bleu in Valais/Switzerland.
June 15, 2025 at 7:15 PM
crisprflydesign.bsky.social
Using #CRISPR to send selected mRNAs to specific subcellular compartments. Exciting technology to probe and harness the spatial organisation of transcripts.

www.nature.com/articles/s41...
Screenshot from the linked paper that used RNA-targeting Cas13 to link mRNAs to motor proteins for intracellular transport.
May 27, 2025 at 6:51 AM
crisprflydesign.bsky.social
CRISPR mutagenesis is also not perfect. A common limitation is generation of genetic mosaics, where only some cells carry gene knockouts. But our new generation of tools substatially improves on that. Described in the preprint below with flies on their way to VDRC:
www.biorxiv.org/content/10.1...
May 26, 2025 at 7:29 AM
crisprflydesign.bsky.social
Why use #CRISPR in #Drosophila when RNAi works so well? Because for some genes well is not good enough.

Check out new preprint from the lab demonstrating a role for Vps15 in Wingless trafficking. Something that was missed in several RNAi screens.

www.biorxiv.org/content/10.1...
Images from the linked preprint showing Wingless stainings in the Drosophila wing imaginal disc. Targeting vps15 with two indepependent RNAi lines (paper also shows the same with a third line) does not result in a phenotype. In contrast, targeting vps15 with two independent sgRNA constructs and Cas9 results in strong accumulation of Wingless protein in perturbed cells.
May 26, 2025 at 7:29 AM
crisprflydesign.bsky.social
Progress 🌻
Picture of a front yard garden. The earth is mostly bare with only a few shrubs visible. The same garden two years later. There is hip-high vegetation including various flowers in full bloom.
May 4, 2025 at 8:44 PM
crisprflydesign.bsky.social
Out of office post.

#takeabreak
#dolomites
April 18, 2025 at 4:36 PM
crisprflydesign.bsky.social
🙄
April 8, 2025 at 7:51 AM
crisprflydesign.bsky.social
That's an interesting twist of the "it's not 'fruit fly', it's 'vinegar fly'" debate.
March 6, 2025 at 10:14 PM
crisprflydesign.bsky.social
Heidelberg today. Together for freedom, diversity, and democracy.
Pictures from a march against fascism in Heidelberg a week before the German general election. Pictures from a march against fascism in Heidelberg a week before the German general election. Pictures from a march against fascism in Heidelberg a week before the German general election.
February 15, 2025 at 4:43 PM
crisprflydesign.bsky.social
Sunday beaking: Yoghurt-Emmer Sourdough.

#bread
Bread loaf after proofing during the bench rest. Same bread after baking.
January 12, 2025 at 9:53 PM
crisprflydesign.bsky.social
This is such an iconic shot. I suspect the other contestants in this competition did not feel particularly optimistic.
Screenshot from a Guardian article about the World Sports Photography award. Overall winner was an iconic image of the surfer Gabriel Medina at the Olympics.
January 10, 2025 at 7:49 AM
crisprflydesign.bsky.social
This is a nice example, because it's know what happens when smo LOF mutations are induced with different efficiency. The currently used Cas9 tools phenocopy induction with medium efficiency, while multiplex Cas12a editing looks exactly like highly efficient induction of known smo LOF clones.
January 7, 2025 at 9:25 PM
crisprflydesign.bsky.social
The power of Cas12a-enabled sgRNA multiplexing for gene disruption.

Today’s example: smoothened
1/3
#CRISPR #Drosophila
Images of Drosophila wings. Control wings expressing CRISPR components exclusively in the germline have normal morphology. Targeting the central hedgehog signaling component smoothened with Cas9 and either one or two sgRNAs results in wings of reduced size and missing and ectopic vein tissue (middle panels). Targeting smoothened with Cas12a+ and four sgRNAs results in very small wings without veins.
January 7, 2025 at 9:25 PM
crisprflydesign.bsky.social
Probably my favorite experiment we ran this year. Screening #CRISPR activity over entire chromosome arms in living animals. From:

www.biorxiv.org/content/10.1...
December 17, 2024 at 12:51 PM
crisprflydesign.bsky.social
💯
"reinforce the need to investigate genetic outcomes [of CRISPR editing] beyond those accessible to short-read target amplicon next-generation sequencing"

from:
www.nature.com/articles/s41...
Adaptation of the popular lamppost meme. A person is searching something in the spotlight of a lamppost and is asked: "Is this where your mutations are?" The reply is "No, but this is what I can amplify by PCR." The implication is that amplicon-based methods for mutation detection are missing all mutation outcomes that are incompatible with PCR (e.g. large deletions, translocations, etc.).
December 3, 2024 at 12:34 PM
crisprflydesign.bsky.social
Disease mutations can be fixed via #CRISPR induced homology directed repair, but efficiency in human cells is typically low. A drug that increases this efficiency has generated much excitement, but the Corn lab now shows it causes genomic instability.

www.nature.com/articles/s41...
Circos plots of CAST-seq-detected chromosomal translocations in edited HSPCs. Addition of the DNA-PKcs inhibitor AZD7648 increases the frequency of translocations.
December 3, 2024 at 12:13 PM
crisprflydesign.bsky.social
To confirm that these phenotypes are real we generated additional sgRNA lines. Once you find good lines the phenotype also appears with Cas9-mediated mutagenesis. We also generated germline mutants in trem, which revealed that the gene is essential. 30/n
Heterogenous effects of trem knock-down with RNAi. While RNAi line BL40881 does not result in a wing phenotype (d), knock-down with line KK109779 results in a shortening of the L5 vein and posterior cross vein (e). (f, f’) Mutagenesis with subsequently made sgRNA pairs under control of a ubiquitous U6:3 promoter and act-Cas9 results in lethality with occasional escapers. Escaper animals show loss of posterior veins.
December 2, 2024 at 3:16 PM
crisprflydesign.bsky.social
This increased efficiency reveals phenotypes previously missed. Example: The gene trade embargo (trem). Targeting trem with Cas9/HD_CFD does not result in wing phenotypes. But multiplex Cas12a targeting results in penetrant defects in vein differentiation (+ some changes in size and shape). 29/n
Phenotype resulting from wing-specific mutagenesis of trem. Specific loss of posterior veins is observed.
December 2, 2024 at 3:16 PM
crisprflydesign.bsky.social
We compared the phenotypic effects of targeting 103 genes for which we also have sgRNA lines in the Cas9 HD_CFD library. The multiplexed Cas12a system induced more severe phenotypes for the majority of wing size regulators. 28/n
Wing size distribution comparing Cas12a+ targeting of known wing morphogenesis genes (orange, n=33) versus control genes (blue, n=18). Clear phenotypic separation demonstrates specificity. See Extended Data Fig. 5 for details. (i) Comparative analysis of wing size phenotypes using Cas12a+/HD12aCFD versus Cas9/HD_CFD systems. Zero values indicate lethal phenotypes. Systems show significantly different effects on tissue size (Wilcoxon signed-rank test, V = 3915, n = 103, p < 0.001, two-tailed).
December 2, 2024 at 3:16 PM