ZahadyV.bsky.social

The essential host genome for Cryptosporidium survival exposes metabolic dependencies that can be leveraged for treatment An arrayed microscopy-based CRISPR screen revealed host genes affecting multiple infection phenotypes of the intracellular parasite Cryptosporidium. Hits in the host cholesterol biosynthesis pathway a...

Our paper has finally graduated from pre-print to peer-reviewed, pretty much unscathed, and is out now! www.cell.com/cell/fulltex...

A common parasite can decapitate human sperm − with implications for male fertility If you’ve handled cat litter or eaten raw meat or unwashed produce, there’s a chance you might have a permanent toxoplasmosis infection spread throughout your body.

Such a fascinating, albeit terrifying study! In case you didn't see it, the study was also covered in @theconversation.com

theconversation.com/a-common-par...

Could the answer to the male fertility crisis be lurking in your cat’s litter tray? Discovery that the world’s most successful parasite can ‘decapitate’ sperm offers a new path to understanding rising infertility among men

Could the answer to the male fertility crisis be lurking in your cat’s litter tray?

Discovery that the world’s most successful parasite can ‘decapitate’ sperm offers a new path to understanding rising infertility among men

✍️ @arthurscottgeddes.bsky.social
www.telegraph.co.uk/global-healt...

Could the answer to the male fertility crisis be lurking in your cat’s litter tray? Discovery that the world’s most successful parasite can ‘decapitate’ sperm offers a new path to understanding rising infertility among men

Excited to see our collaborative research featured in the Telegraph! Grateful for the amazing team effort behind it and hopeful it helps raise awareness about toxoplasmosis in men. Thanks @arthurscottgeddes.bsky.social for highlighting our research! www.telegraph.co.uk/global-healt... #Toxoplasmosis

Could the answer to the male fertility crisis be lurking in your cat’s litter tray? Discovery that the world’s most successful parasite can ‘decapitate’ sperm offers a new path to understanding rising infertility among men

It turns out the world’s most successful parasite can ‘decapitate’ sperm. For @telglobalhealth.bsky.social I wrote about the implications of this discovery for our understanding of the male infertility crisis. With thanks to @zahadyv.bsky.social and Bill Sullivan
www.telegraph.co.uk/global-healt...

Uncovering biomarkers for chronic toxoplasmosis detection highlights alternative pathways shaping parasite dormancy | EMBO Molecular Medicine imageimageDespite their clinical relevance, bradyzoite-filled cysts - the hallmark of chronic toxoplasmosis - are largely overlooked in current diagnostics. This study highlights bradyzoite serologica...

🧵 Ever wondered what Toxoplasma is doing in your brain years after that undercooked steak 🥩 or a sip of contaminated water? Turns out, it's been hiding in your brain 🧠and we finally have a way to spot it. New study just dropped in EMBO Molecular Medicine 👇
doi.org/10.1038/s443...

Thanks Jean. I'm glad that you like it ☺️

7/ Why does this matter? Shows T. gondii can rapidly invade male reproductive organs reveals a novel mechanism of sperm damage and raises questions about potential impacts on male fertility. Is it interesting? check out the above link #Toxoplasma #ReproductiveHealth#Microbiology #Parasitology

6/ Surprisingly, ROS levels did not increase, and the acrosome reaction (key for fertilization) was unaffected. This suggests T. gondii damages sperm via direct mechanical disruption and mitochondrial dysfunction.

5/ Is this damage caused by direct contact or secreted molecules? We ruled out soluble factors—only direct parasite contact induced sperm decapitation. Extracellular vesicles (exosomes) also had no effect and no DNA fragmentation. But apoptosis & necrosis increased. MMP dropped sharply.

4/ Scanning electron microscopy (SEM) revealed: Parasites attaching to sperm heads/tails Twisted, coiled tails. Holes in sperm heads (!) and Some heads were completely emptied of content

3/ Next, we tested how T. gondii affects human sperm. After just 5 minutes of exposure: 22% of sperm lost their heads (vs. 1.6% in controls). By 15 min, headless sperm increased 8-fold!.

2/ But are these parasites still infectives? Yes. We extracted infected tissues, injected them into healthy mice, and confirmed new infections via PCR. The parasites remain viable and infectious!.

1/ T. gondii effects on male reproduction are poorly understood, and here we reveals how T.g invades testes, epididymis, and even damages. After 2 days tachyzoites were detected in both testes and epididymis with immune cell infiltration and structural damage in seminal tubules.

FEBS Press Toxoplasma gondii tachyzoites injected intraperitoneally crossed the blood-testes barrier, appearing in testes/epididymis by day 6 post-infection. In vitro exposure caused increased sperm necrosis/ap...

🚨New Research: Adverse impact of acute Toxoplasma gondii infection on human spermatozoa- The FEBS Journal - febs.onlinelibrary.wiley.com/doi/10.1111/.... Thanks to @mariaefrancia.bsky.social Lab and all wonderful people who collaborate to make this possible. Here below what we found :).

👌🏽

GRA12 is a common virulence factor across Toxoplasma gondii strains and mouse subspecies - Nature Communications CRISPR screens reveal Toxoplasma’s GRA12 as a strain- and mouse species-transcendent virulence factor. GRA12 protects parasites from IFNγ-activated macrophage clearance and parasitophorous vacuole col...

🎉 Finally online 🎉 GRA12, the first identified common virulence factor across Toxoplasma strains and murine subspecies! Check this improved manuscript after reviewers’ helpful suggestions www.nature.com/articles/s41...

Congratulations Francesca!🎉

Congratulations! Well deserved it

The Toxoplasma rhoptry protein ROP55 is a major virulence factor that prevents lytic host cell death Nature Communications - Ruivo et al uncover a Toxoplasma survival mechanism conserved across different cell types and species. By repressing NF-kB activation and lytic host cell death pathways, the...

Delighted to share our study on a major Toxoplasma virulence factor that prevents lytic host cell death.
Many thanks to @parafrap.bsky.social for support, constructive reviews and all labs involved: Melissa Lodoen, Hiba El Hajj, @gissotlab.bsky.social, Karine Le Roch
Link : rdcu.be/d6m3G

Finally, I would like to thank all authors,
@ivanconejeros.bsky.social, and
@moritztreeck.bsky.social for allowing us to work with T.g. HCE1 and MYR1 mutants.

5/Host cells activate the ATM DNA damage response mechanism despite DNA damage. Other genome instability signs found were cytokinesis failure and micronuclei formation, which were observed early during infection. Interestingly, these effects proved independent of MYR1 or HCE1.
#CellBiology

4/ Strikingly, T. gondii-induced DNA damage begins just 15 minutes post-infection. This damage, marked by γH2AX foci, predominantly affects cells in the S-phase and is independent of reactive oxygen species (ROS).
#GenomeInstability

3/ MYR1 drives the translocation of parasite effectors into the host nucleus, leading to cell cycle arrest and a MYR1-dependent DNA damage response. These findings highlight MYR1's central role in parasite-host manipulation.
#DNAResearch #Parasitology

2/ Within 15 minutes of infection, T. gondii causes host cells to arrest in the S-phase of the cell cycle. This rapid effect, seen in endothelial cells, relies on the parasite’s MYR1 protein but not HCE1.
#CellCycle #HostPathogenInteractions

1/ Toxoplasma gondii manipulates host cells early in infection, arresting the cell cycle and triggering DNA damage. This breakthrough reveals a MYR1-dependent mechanism driving genome instability. Let's dive in!
#ToxoplasmaGondii #ParasiteBiology

Toxoplasma gondii infection induces early host cell cycle arrest and DNA damage in primary human host cells by a MYR1-dependent mechanism Communications Biology - Early T. gondii infection induces host S-phase arrest and DNA breaks, with binucleation and micronuclei formation observed by 3 h p.i., indicating genomic...

📣New Study Alert!
Toxoplasma gondii arrests host cell cycle early p.i. in a MYR1-dependent manner, inducing DNA damage and genome instability. This work unveils new insights into host-parasite interactions and the mechanisms driving cell cycle modulation.
rdcu.be/d3IxO #Toxoplasma #CellCycle

Schematic showing the experimental outline for a full genome arrayed CRISPR screen. 384-well plates containing cells with an arrayed crRNA library are infected with Cryptosporidium parasites, which undergo asexual rounds of replication intracellularly, followed by sexual development to male and female forms. Plates are then fixed and immunolabeled to detect all parasites, female parasites, host actin recruited to parasite vacuoles, and host nuclei. Three z-stacks were imaged by high content microscopy to detect apically located parasites as well as host cell actin and nuclei.

Have you ever wondered how knocking out every single gene in the human genome, one by one, might affect your intracellular pathogen of interest? We did, & boy was it a wild ride! Happy to share our preprint discovering the essential host genome for Cryptosporidium -

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

Cryptosporidium is an important public health threat, and it deserves better genetic tools to study it! Here we’ve developed a targeted in vivo CRISPR genetic screen to identify parasite genes required for survival and virulence…
www.biorxiv.org/content/10.1...

📣📣📣
Come join us and set up your team in the I2BC Cell Bio Dept!

You will find great science, diverse topics and models, spacious labs, supportive environment, and fun colleagues. We are a short (train) ride south of Paris.

Please DM me with any questions and help us spread the word 🙏