Jesus Alvarado-Valverde

I’m very excited to share that our paper has been recently published in Cell Stem Cell! 🎉 🧫

In this study, using high-content imaging–based organoid screening, we discovered growth media conditions that drive differentiation into functional pancreatic acinar cells.

doi.org/10.1016/j.st...

Making human pancreatic acinar cells Dresden researchers develop novel methods to create acinar cells, which are involved in the formation of pancreatic cancer.

The group of @anne-grapin.bsky.social developed methods to create functional acinar cells, which are involved in the formation of pancreatic cancer. Rashmiparvathi Keshara, Karolina Kuodyte, and the TDS facility used image-based screen & robust analysis pipeline. www.mpi-cbg.de/news-outreac...

Short linear motifs - Unexplored players driving Toxoplasma gondii infection Pathogens infect hosts by interacting with host proteins and exploiting their functions to their advantage. Short linear motifs, small functional regions within intrinsically disordered protein regions, are common mediators of host-pathogen protein interactions. While motifs have been more extensively studied in viruses and bacteria, the extent to which eukaryotic unicellular parasites use motifs during infection remains unexplored. Toxoplasma gondii is a widespread intracellular Apicomplexan parasite capable of infecting all warm-blooded animals and invading any of their nucleated cells. Toxoplasma's secreted proteins are key in interacting with host proteins during infection, making them potential sources for motifs. To highlight the role of motifs in Toxoplasma gondii infection, we curated 20 known motif instances in Toxoplasma proteins from the scientific literature. To identify more motifs in Toxoplasma secreted proteins, we developed a computational pipeline that annotates putative motif matches with structural and functional features. Through this approach, we identified a set of 27,832 motif matches in 296 secreted proteins. We highlight strategies for further prioritisation of likely functional motif matches by focusing on integrin motifs, degrons and TRAF6-binding motifs. We subjected four predicted TRAF6-binding motifs to experimental validation, supporting the predicted motifs in the Toxoplasma proteins RON10 and GRA15. Our motif predictions provide a valuable resource for generating hypotheses and designing experiments to study infection mechanisms. The characterisation of motifs in Toxoplasma will be key to understanding the molecular principles underlying its broad host range and more comprehensive Apicomplexan infection strategies. ### Competing Interest Statement The authors have declared no competing interest. Deutsche Forschungsgemeinschaft, 449991970

New preprint! Here, we highlight the role of motifs during the Toxoplasma host cell invasion, predict thousands of motifs in its effector proteins, and validate the binding of TRAF6 motifs. Our results are intended to catalyse further research on motifs and parasites.
www.biorxiv.org/content/10.6...

Really important discussion also applicable to UK research funding: the application system is enormously wasteful of time, energy and talents

Toxoplasma effector TgROP1 establishes membrane contact sites with the endoplasmic reticulum during infection - Nature Microbiology The Toxoplasma gondii effector TgROP1 mimics host factors to bind VAPA/B, thereby establishing parasite–host ER contact sites.

During host cell invasion, Toxoplasma mimics the FFAT motif and repurposes it to associate its parasitophorous vacuole to the endoplasmic reticulum!

I'm happy to have been part of this work! Congratulations to Chahat Mehra and Lena Pernas for all the hard work!
www.nature.com/articles/s41...

Toxoplasma effector TgROP1 establishes membrane contact sites with the endoplasmic reticulum during infection - Nature Microbiology The Toxoplasma gondii effector TgROP1 mimics host factors to bind VAPA/B, thereby establishing parasite–host ER contact sites.

#NewResearch

The Toxoplasma gondii effector TgROP1 mimics host factors to bind VAPA/B, thereby establishing parasite–host ER contact sites.

#MicroSky 🦠

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

Variant characterization in the intrinsically disordered human proteome Variant effect prediction remains a key challenge to resolve in precision medicine. Sophisticated computational models that exploit sequence conservation and structure are increasingly successful in t...

Check out our latest research!

Using a motif predictor and AlphaFold models, we designed experiments to validate their interaction interfaces and tested the effects of uncharacterized variants on binding, then predicted the effects of hundreds of them.

www.biorxiv.org/content/10.1...

Remember to tune it at 6pm CET May 12 for the next seminar in our series with Prof. Tony Hunter (@salkinstitute.bsky.social) and Dr. Jesús Alvarado-Valverde (@jesusav.bsky.social).

Register to attend:
tinyurl.com/PMCseminar2

Join us at 6pm CET May 12 for the next seminar in our series with Prof. Tony Hunter (@salkinstitute.bsky.social) and Dr. Jesús Alvardo Valverde (@jesusav.bsky.social).

Register to attend:
tinyurl.com/PMCseminar2
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