Institut Necker Enfants Malades (INEM) is a biomedical research center located on the Necker campus. It benefits from numerous state-of-the-art core facilities. The Campus has a long-standing reputation for scientific excellence and key pioneering medical contributions (transplantation, biotherapy, gene therapy). It provides a vibrant environment for basic research and translational innovation.

The host laboratory

The “Host-Pathogen Integrative Biology” team, led by Mathieu Coureuil objective is to enhance our understanding of the pathogenesis of systemic infections, enabling us to identify novel targets for prevention and treatment, with a focus on (i) the mechanisms and consequences of the interaction of extra-cellular bacterial pathogens with endothelial cells, and (ii) Staphylococcus aureus pathogenesis, which is one of the deadliest bacteria in Western countries.

About the project

Sepsis is a severe form of organ dysfunction, with high morbidity and mortality rates, worldwide. Cardiac dysfunction is one of the most common and severe complications of sepsis and directly affects patient mortality, as normal cardiac function is crucial for adequate organ perfusion. How sepsis induces acute cardiomyopathy is complex and characterized by numerous inter- and intra-cellular dysfunctions. The underlying mechanisms leading to cardiomyocyte acute dysfunction in the context of sepsis remains largely elusive. With the emergence of antibiotic-resistant bacteria, the number of individuals affected by bacteria-induced sepsis is bound to increase dramatically, representing an unmet medical need.

The overall objective of our project is to better understand cardiomyocyte death and/or dysfunction and therefore acute cardiac insufficiency in the context of bacterial sepsis, with a focus on N. meningitidis infection. For this, we leverage a consortium expertise in microbiology, vascular biology, cardiac biology, and critical care medicine.

Our main objectives are: (1) to identify factors specifically released by endothelial cells during meningococcal infection that will be involved in lethal sepsis. Will focus on endothelium-derived extracellular vesicles produced as a result of N. meningitidis interaction with endothelial cells, a specific feature of this infection; (2) to define the molecular and cellular impact of meningococcal infection on vascular and cardiac dysfunction, which ultimately leads to animal death.

Research keywords: Cardiovascular Dysfunctions; Endothelium-Derived Microparticles; Host-Pathogen Interactions; Sepsis; Mouse models

Your profile

The applicant should be a highly motivated postdoctoral candidate with a PhD degree in “Cardiac physiology” or “Bacteria associated sepsis and mouse physiology” and a high-quality track record. He/she should have a strong background in performing research in mouse and in vitro models.

The position is funded for 2 years (1+1). Salary will be according to experience following INSERM regulation.

How to apply

The candidate should send a curriculum with a brief statement of research experience, technical expertise and interests, and one or two references to Mathieu Coureuil or Anne-Sophie Armand.

Mathieu Coureuil, PhD, @email

Anne-Sophie Armand, PhD, @email

Selected references from the PIs, relevant to this application

Ziveri J, Le Guennec L, Dos Santos Souza I, Barnier JP, Walter SM, Diallo Y, Smail Y, Le Seac'h E, Bouzinba-Segard H, Faure C, Morand PC, Carel I, Perriere N, Schmitt T, Izac B, Letourneur F, Coureuil M, Rattei T, Nassif X, Bourdoulous S. Angiopoietin-like 4 protects against endothelial dysfunction during bacterial sepsis.
Nat Microbiol. 2024 Aug 5.

Schönherr-Hellec S, Chatzopoulou E, Barnier JP, Atlas Y, Dupichaud S, Guilbert T, Dupraz Y, Meyer J, Chaussain C, Gorin C, Nassif X, Germain S, Muller L*, Coureuil M*. Implantation of engineered human microvasculature to study human infectious diseases in mouse models.
iScience. 2023 Feb 27;26(4):106286. 

Barnier JP, Euphrasie D, Join-Lambert O, Audry M, Schonherr-Hellec S, Schmitt T, Bourdoulous S, Coureuil M, Nassif X, El Behi M. Type IV pilus retraction enables sustained bacteremia and plays a key role in the outcome of meningococcal sepsis in a humanized mouse model. 
PLoS Pathog. 2021 Feb 16;17(2):e1009299.

Virion Z, Doly S, Saha K, Lambert M, Guillonneau F, Bied C, Duke RM, Rudd PM, Robbe-Masselot C, Nassif X, Coureuil M* and Marullo S*. Sialic acid mediated mechanical activation of β2 adrenergic receptors by bacterial pili. 
Nat Commun. 2019 Oct 18;10(1):4752

Denis K, Le Bris M, Le Guennec L, Barnier JP, Faure C, Gouge A, Bouzinba-Ségard H, Jamet A, Euphrasie D, Durel B, Barois N, Pelissier P, Morand PC, Coureuil M, Lafont F, Join-Lambert O, Nassif X, Bourdoulous S. Targeting Type IV pili as an antivirulence strategy against invasive meningococcal disease.
Nat Microbiol. 2019 Mar 25. doi: 10.1038/s41564-019-0395-8.

Rivagorda M, Romeo-Guitart D, Blanchet V, Mailliet F, Boitez V, Barry N, Milunov D, Siopi E, Goudin N, Moriceau S, Guerrera C, Leibovici M, Saha S, Codogno P, Morselli E, Morel E, Armand AS, Franck Oury F. A primary cilia-autophagy axis in hippocampal Neurons is essential to maintain cognitive resilience. 
Nat Aging (accepted).

Dirkx E, Monika M. Gladka MM, da Costa Martins PA, Philippen LE, Armand AS, Leptidis S, Kinet V, el Azzouzi H, Bourajjaj M, Olieslagers S, van der Nagel R, de Weger R, Bitsch N, Kisters N, Seyen S, Chanoine C, Heymans S, Volders P, Thum T, Dimmeler S, Cserjesi P, Eschenhagen T, De Windt LJ. (Post) -transcriptional reactivation of the bHLH transcription factor Hand2 in the postnatal myocardium causes cardiac dilation and dysfunction. 
Nat. Cell Biol. 2013. 15:1282-1293.

De Majo F, Martens L, Hegenbarth JC, Rühle F, Hamczyk MR, Nevado RM, Andrés V, Hilbold E, Bär C, Thum T, de Boer M, Duncker DJ, Schroen B, Armand AS, Stoll M, De Windt LJ. Genomic instability in the naturally and prematurely aged myocardium.
Proc Natl Acad Sci U S A. 2021. 118 : e2022974118.