Hôte : B. Fromy 

 

L. Dumoutier will give a brief introduction on the discovery of IL-22 and its receptors to date. This will be followed by their results demonstrating its harmful role in psoriasis, dermatitis and squamous cell carcinoma, as well as its beneficial role in epithelial regeneration during colitis. Due to IL-22's ambivalent role, they are developing a strategy to block its harmful effects while preserving its beneficial ones. They are fortunate that IL-22 induces massive STAT3 activation via two mechanisms: the first is the classic receptor tyrosine-dependent mechanism, and the second is an alternative, receptor tyrosine-independent mechanism. They believe that characterising this alternative mechanism will enable us to develop new targeted therapies with fewer side effects.

 

Hôte : S. Mérabet

 

My lab is interested in the mechanistic basis of evolutionary diversification of animals in response to the environment. As a model system, we use closely-related drosophilid species with distinct niches, which enables us to identify genetic and cellular changes underlying ecologically-relevant adaptations. I will present two unpublished projects. The first is concerned with the functional diversification of the odour-tuning properties of volatile acid-sensing neurons in drosophilids, which has led us to discover a novel type of signalling mechanism in peripheral chemical detection. The second is concerned with the evolution of tolerance to a natural fruit toxin, in which we combined experimental evolution in animals and CRISPR-based mutant screens in cell culture to identify new resistance loci.

 

 

Hôte : Marie-Cécile Caillaud

 

 

 

Le milieu intracellulaire est un environnement dense et hétérogène qui module profondément le comportement des biomolécules. Il influence le repliement des protéines, leurs interactions et les équilibres réactionnels. Pourtant, la majorité des études expérimentales et de simulation sont encore réalisées dans des conditions diluées. Afin de dépasser cette limite, nous combinons la RMN in-cell et les simulations de dynamique moléculaire atomistique (MD) pour étudier le comportement de la protéine modèle Gb1 dans des environnements intracellulaires. Nos simulations apportent des informations structurales et dynamiques qui complètent les observations in-cell RMN et permettent d’interpréter des changements conformationnels subtils induits par l’encombrement macromoléculaire. Cette approche intégrative souligne l’importance d’étudier les protéines dans des environnements physiologiquement réalistes.

 

During bacterial infection, macrophages successively encounter and engulf live and killed microbes, and trigger appropriated host responses to eradicate the threat and restore tissue homeostasis. Despite the critical role of phagocytosis during this event, the fate of phagocytosed microbial cargo and its impact on host cell is poorly understood. Our investigation reveals that phagocytosis of bacteria provides bioenergetic and biosynthetic precursors that are differentially utilized by macrophages depending on microbial viability. This highlights the capacity of phagocytic cells to adjust their cellular metabolism to the ‘fueling’ capacity of the ingested cargos and how, together with the sensing of microbial viability, it regulates immunometabolic adaptations to adjust host response intensity to the course of microbial infection.

 

 

Pierre-Alix Dancer                              

 

Hôte : C. Maisse

 

 

 

Owen Randlett (MELIS-INMG; Lyon)                             

         

 

Hôte : A. Piazza & D. Jost 

 

Nucleosomes, the fundamental units of DNA folding in eukaryotes, play critical roles in chromosome structure and gene regulation. Our research group, collaborating with experimental teams at the Pasteur Institute, investigates the sequence-based mechanisms that determine specific nucleosome positioning across genomes. We developed a computational deep mutational screening approach to quantify how individual genetic mutations affect nucleosome positioning in Saccharomyces cerevisiae. The results can not only guide the design of modified yeast genomes but also provides insights into the sequence-dependent mechanisms of nucleosome positioning in living cells. Our computational approach was then applied to yeast strains containing artificial bacterial chromosomes, demonstrating the predictive power of our model in characterizing chromatin structures across diverse genomic contexts. We next proposed a new computational method integrating kinetic Monte Carlo modeling and deep learning predictions. This approach enables the rational design of novel DNA sequences with customized nucleosome periodicities in yeast. The engineered sequences can accommodate periodicities significantly larger than the natural yeast period, offering new opportunities to explore chromatin structure-function relationships. Finally, we extended our methodology to mouse embryonic stem cells, identifying key sequence elements that drive nucleosome positioning. Our work reveals islands of regularly spaced nucleosomes around nucleosome positioning regions, uncovering the relationships between nucleosome positioning, transcription factor footprints and DNA repeats.

Hôte : D. Lavillette  

 

The COVID-19 pandemic, along with its etiologic agent, SARS-CoV-2, has drawn increasing attention to the long-term health impacts of acute viral infections. While chronic inflammation is known to negatively affect bone marrow homeostasis and hematopoiesis, the effects of post-acute sequelae of viral infections on the bone marrow niche are not well understood. In this seminar, we will present evidence of significant bone marrow hematopoietic dysregulation in the context of post-acute sequelae of COVID-19 (PASC). We will first introduce a novel mouse model of PASC, RAB/6N, and its unique ability to recapitulate persisting systemic inflammation and immune dysregulation months post SARS-CoV-2 infection. We will then characterize the impact of PASC on bone marrow hematopoiesis in this model, and expand these findings to other viral infections associated with long-lasting sequelae. Finally, we will discuss how mice engrafted with a human immune system could enable us to investigate PASC-associated bone marrow hematopoietic dysregulation in a human context. 

 

Hôte : J. Lamartine

 

Hôte : D. Lavillette

 

In this presentation it will be discussed how S.aureus adapt to stress encountered during an infection in the host and how this affect bacterial survival and persistence.