Recherche - Interdisciplinarité- 2026

Résumé:

Le projet HET-FLOW a pour objectif de développer des outils de biologie cellulaire à haute résolution faisant intervenir la cytométrie en flux afin de détecter simultanément, dans une même cellule, des transcrits et des protéines, et éventuellement d’autres caractéristiques fonctionnelles telles que le potentiel de membrane.

Nous utiliserons le modèle Lactococcus cremoris, une bactérie fermentaire possédant néanmoins des éléments de chaîne respiratoire, dont un, le cytochrome bd, présente une hétérogénéité de production d’une cellule à l’autre dans certaines conditions environnementales. Afin de déterminer si cette hétérogénéité protéique est liée à une hétérogénéité au niveau transcriptionnelle, nous transposerons la méthode de flow-FISH déjà établie pour les cellules eucaryotes au cellules bactériennes. Nous utiliserons également des marqueurs fluorescents du potentiel de membrane afin de déterminer si l’hétérogénéité de production de protéines se traduit par une hétérogénéité fonctionnelle, testant la capacité respiratoire des cellules. La finalité sera de corréler production de protéine, expression des gènes et fonctionnalité de la chaine respiratoire au niveau de la cellule unique.

Une fois mis au point sur la question relative à notre modèle, les outils développés seront destinés à être mis à disposition de la communauté des microbiologistes afin notamment de permettre l’étude de la variabilité phénotypique et des stratégies d’adaptation bactérienne.

Résumé:

Hunting for Our Microbial Ancestors—The Asgard Archaea

Why Study Asgard Archaea?

Asgard archaea are a group of microbes discovered less than a decade ago, named after Norse gods (Loki, Thor, Odin, Heimdall) because their discovery revolutionized our understanding of how complex life evolved. These microbes are our closest known relatives among the archaea, and they carry genes usually found only in eukaryotes—organisms with complex cells, such as animals, plants, and fungi. It suggests that Asgard archaea might be the living descendants of the ancient microbes that gave rise to all complex life on Earth.

What Do We Know So Far?

Only two Asgard species have been grown in the lab, respectively by a Japanese and an Austrian team: ‘Candidatus Prometheoarchaeum syntrophicum’ lives in partnership with other microbes, forms long cellular extensions, and may have played a key role in the origin of eukaryotes (Imashi et al., 2020).   ‘Candidatus Lokiarchaeum ossiferum’: Thrives at 20°C, has a larger genome, and shows complex internal structures, possibly thanks to a primitive cytoskeleton (Rodrigues-Oliveira et al. 2023). These findings support the idea that eukaryotes may have emerged from a fusion between an Asgard archaeon and a bacterium over 2 billion years ago.

Our Project: Cultivating Heimdallarchaeota, Our Closest Microbial Relatives

Microbiologists at the MIO (MEB team) lab have successfully enriched cultures of Heimdallarchaeota—the Asgard group most closely related to eukaryotes—from hydrothermally heated sediments. These microbes live in extreme conditions (45–55°C, acidic, oxygen-free). Scientists used in situ microbial culture devices to enrich Asgard archaea. Back in the lab, they could maintain the growth of these microbes under controlled conditions. Yet Heimdall archaea represent a tiny fraction of the microbial cultures. Still, their cells could be visualized by specific microscopy techniques (FISH-confocal microscopy) at the BIAM lab, thanks to collaboration with researchers of the BEAMM team.

Our Goals in the Asgardomics project:

1) Obtain the first stable culture of Heimdallarchaeota to study their cell structure and metabolism.

2) Understand how these microbes might have given rise to eukaryotes.

3) Test hypotheses about the evolution of complex life.

To achieve these objectives:

We will use innovative and complementary Methods

-  Dedicated culture methods, including novel in situ enrichments and middle-throughput techniques

- Deep sequencing of enrichment cultures (metagenomics) for bioinformatic reconstruction of Asgard archaea genomes, which will help us decipher their metabolism and lifestyle and shed light on the evolutionary relationship with other archaea and eukaryotes.

-  Advanced microscopy to visualize cell structures, like the primitive cytoskeleton.

Challenges and Stakes

Challenge: These microbes are a minority in their natural ecosystem, grow very slowly, and are fragile.

Originality: No one has yet succeeded in cultivating Heimdallarchaeota.

Potential: A stable culture could unlock mysteries about the origin of eukaryotes

What’s Next?

If successful, these archaea could become a global research model, attracting international collaborations and opening new avenues for understanding the evolution of early eukaryotic life.

Résumé:

Platelets are small blood cells that help stop bleeding by forming clots, but they can also cause life-threatening, clots that stop blood flow to tissues and organs leading to heart attacks or strokes. Most current anti-platelet drugs reduce clotting, but also increase the risk of bleeding, which is a major problem.

In this project, researchers present a new strategy to prevent harmful clot formation without severely affecting clotting. They developed innovative bispecific antibody molecules called cis-acting platelet receptor inhibitors (CAPRIs) that work by limiting specific platelet activation signals rather than completely blocking these critical pathways. CAPRIs bring together a natural inhibitory receptor on platelets (G6B) with activating receptors that are responsible for thrombus formation, including the collagen and immunoglobulin receptors GPVI and FcgRIIA (CD32A), respectively.

By doing this, CAPRIs effectively prevented platelet activation caused by collagen or immune complexes in several disease-related models, including arterial thrombosis, heparin- and vaccine-induced thrombocytopenia (reduced platelet count) and thrombosis (HIT and VITT), antiphospholipid syndrome (APS), and sepsis. Importantly, these effects were seen under conditions that closely mimic blood flow in arteries.

Overall, this research reveals that CAPRIs can selectively block harmful platelet activation pathways. This approach could lead to a new class of anti-thrombotic treatments that are effective at preventing pathological blood clotting while potentially causing fewer bleeding side-effects than current therapeutics.

Projet inter-institut IM2B - ICI