EMBL-Institut Pasteur: A European Partnership in Infection Biology

Flagship Research Projects 

Several joint projects exemplify the potential of this collaboration. 

Towards a mechanistic understanding of NK cell memory co-supervised by Mélanie Hamon, head of the Chromatin and Infection unit. 

This study aims to understand natural killer (NK) cell memory in bacterial infections, using as a model Streptococcus pneumoniae, the leading cause of bacterial pneumonia worldwide. Traditionally associated with innate immunity, NK cells have been shown to develop memory-like properties which could be harnessed for new immunotherapy approaches against bacterial pathogens. The study’s goals are to identify specific marker genes for memory NK cells and to investigate key chromatin regulators essential for NK cell memory maintenance, ultimately contributing to an unprecedented understanding of this process during bacterial infection. 

Exploring the role of translation landscapes in Salmonella pathogenicity and antibiotic resistance during the colonization of diverse host intracellular niches co-supervised by Jost Enninga, head of the Dynamics of Host-Pathogen Interactions unit. 

This project aims to elucidate the intracellular Salmonella Typhimurium (S.Tm) translation landscapes to better understand differences related to the colonisation of diverse host-cell niches. We will employ cryo-correlative light and electron microscopy alongside subtomogram averaging to structurally analyze S.Tm ribosomes in distinct growth states of the pathogen that are related to specific intracellular localization within infected cells. This innovative approach will allow us to simultaneously pinpoint bacterial localization and ribosomal conformations, shedding light on the pathogen’s adaptation strategies. Finally, we will assess the impact of ribosome-targeting antibiotics on the translation machinery across the different niches. This study will deepen our understanding of intracellular bacterial pathogenesis, identify factors contributing to antibiotic resistance, and explore novel therapeutic strategies.

Bioengineering vascularized human microlivers for malaria infection co-supervised by Liliana Mancio-Silva, head of the Plasmodium Infection and Transmission group. 

This project will bioengineer new in vitro platforms that capture the complexity of the human liver to investigate host-parasite interactions with the liver microvasculature and their impact on hepatocyte infection. Specifically, we aim to characterise parasite interactions with engineered human 3D liver microvessels and to build a vascularised human microliver to shed light on receptor-ligand interactions driving early infection. This project will lay the foundation for a deeper understanding of potentially targetable host-pathogen interactions and generate a preclinical platform aimed at evaluating therapeutic interventions. 

Exploring new therapeutic opportunities against mpox virus co-supervised by Pablo Guardado-Calvo, head of the Structural biology of infectious diseases five-year group.

Today, there are concerns that smallpox re-emerge as a bioweapon or the emergence of zoonotic orthopoxviruses, as seen with the mpox outbreaks in 2022 and 2024. Current treatments for poxvirus infections are effective but limited: first-generation vaccines are discontinued and modern vaccines are challenging to produce on a large scale and fail to produce long-term immunity. Tecovirimat, the primary treatment for mpox, is vulnerable to viral resistance as a single mutation in the viral phospholipase F13 may confer resistance to the drug. There is a pressing need for developing broad-spectrum antivirals to treat mpox and other diseases caused by orthopoxviruses. 

This project aims to combine the expertise of EMBL and the Institut Pasteur to establish proof of concept for novel therapeutic strategies that could lead to the development of new antivirals targeting different pockets of the F13 protein.