Structure Content

Intracellular bacterial pathogens enter host cells to form a bacterial containing vacuole (BCV). Then, the BCV matures or ruptures leading to two distinct pathogen-dependent intracellular niches; one vacuolar and one cytosolic. The specific intracellular […]

ILT4 (immunoglobulin-Like Transcript 4) is an immune checkpoint receptor mainly expressed by myeloid immune cells. In cancer context, ILT4 participates in tumor development by maintaining a pro-tumoral immuno-microenvironment and directly promoting tumor cell proliferation. […]

The outer membrane (OM) is an essential element in Gram-negative (diderm) bacteria. Its integrity is maintained by the control of lipids asymmetry via LPS and phospholipids transport by the Lpt and Mla systems, respectively. […]

Nearly all motile bacteria are able direct their motility to actively seek out favorable conditions (Hazelbauer et al., 2008). Most commonly, these bacterial cells use flagella to swim through liquid environments or swarm on […]

Bacteria are able to sense environmental changes in their surroundings and adapt themselves, both structurally and metabolically, in order to survive. These cells are able to switch between free-living states, sessile states in biofilms, […]

This ANR-NSF international project (PRCI) is led by Nikhil Malvankar of Yale University and Olivera Francetic of Institut Pasteur. The aim of the project is to explore the mechanism of assembly and ultrafast electron […]

Bacteria are nearly ubiquitous, play vital roles in industry and the environment, and are crucial factors for health and disease of all organisms. They are also small, tractable cells that are ideal to study […]

Microtubules are cytoskeletal elements that are central to cell life. Their primary components are tubulins and undergo various post-translational modifications acting as a tubulin code. Here, we wish to investigate a main modification called […]

The project funded by the Human Frontiers Science Program has been rewarded in May 2023 to an international and interdisciplinary team led by Nikhil Malvankar (Yale University, USA), Lisa Craig (Simon Frazer University, Canada), […]

Gram-negative bacteria are delimited by an envelope composed of two membranes (the outer and the inner-membranes) separated by the periplasmic space. This envelope includes macromolecular machines that ensure and regulate exchanges between the bacterium […]

Gastric cancer is the fourth cause of cancer-related death and the fifth most common diagnosed cancer worldwide. Gastric cancer still remains an important healthcare challenge with 1 million new cases per year. Despite its […]

The active site of type II secretion nanomachine: architecture, mechanism and specificity Objectives The goal of the project is to determine the structure of the central subcomplex of the Type II secretion system called […]

A common phenomenon in most microbial infections is the attenuation of the host’s immediate immune response, allowing for long-term colonization. We and others have shown that many pathogens achieve this by manipulating the epigenetic […]

Homodimeric VHHs offer new perspectives for in vivo immunodiagnosis. Because of their small size of about 12-14 kDa, VHHs rapidly pass the renal filter, which has a cutoff of about 60 kDa, resulting in […]

AEGIS is a Marie Skłodowska -Curie Innovative Training Network (ITN) for early stage researchers (ESR) funded by the European Commission under the H2020 Programme the EU framework programme for research and innovation. The principal […]

Design of Antiviral drugs for Bronchiolitis Virus using a novel therapeutic target.

Protein structure determination is crucial for understanding protein function, as it paves the way to the discovery of new drugs and of new approaches to control pathological biological processes. The recent advances in structural […]

Organic synthesis, still the limiting factor of Medicinal Chemistry? This ongoing project is based on our reviews (1-3) on the inhibitors of the ATPase functions of human heat shock protein 90 (HSP90) or bacterial […]

Bacteria display several mechanisms to adapt to their host-environment and successfully colonise it. One important mechanism of adaptation concerns the regulation of gene expression in response to external signals such as the presence of […]

New therapeutic strategies are needed to combat the pandemics and the spread of multidrug resistant form of tuberculosis. This collaborative project between our group and Institut Pasteur of Korea aims to decipher the molecular […]

This project aims to describe the hydrodynamic and thermodynamic properties of the CyaA toxin and the conformational changes it undergoes during its translocation process across the lipid membranes of Bordetella pertussis (secretion) and of […]

About Bip:Bip The project Bip:Bip promotes an integrated use of known and modelled three-dimensional structures of proteins as an aid in complete genome annotation. The architectural organization of biological macromolecules is essential for the […]

Centre for the Analysis of Complex Systems in Complex Environments About CACSICE Cells function through transient interactions of macromolecular complexes. Understanding fully the dynamic processes of life at the molecular level requies understanding the […]

  Synthetic oligosaccharides are designed and used to identify immunodominant epitopes of bacterial polysaccharide antigens. Conjugates of the most promising oligosaccharides are developed as potential  vaccines. Focus is on diarrheal diseases. Shigellosis – bacillary […]

At the forefront of the rising fields of Chemical and Synthetic Biology, CarbUniVax is a multidisciplinary project sitting at the frontier between Glycosciences and Vaccinology. A multidisciplinary strategy is proposed that challenges ambitious goals […]

Concerted effort to address rational drug design against Chagas disease Through a multidisciplinary approach that combine medicinal chemistry, structural bioinformatics, molecular docking and immunobiology of the infectious process, we identified two new inhibitors of […]

Towards the development of diagnostic tests for Chagas disease and post-treatment monitoring by the use of specific markers of the parasite Trypanosoma cruzi and prognostic biomarkers of chronic phase of infection. Current methods available […]

During the last decades, structural biology allowed to incredibly improve the information on the biological objects, from single biomolecules to molecular assemblies, and to get a better description  of the physics underlying the interactions […]

  We recently demonstrated the existence of a phosphorylation-dependent control of glutamate metabolism in mycobacteria, in collaboration with H. O’Hare’s group in Leicester (O’Hare et al., 2008). Our results were supported by similar observations […]

  CORONABODIES : Production of SARS-CoV-2 nucleoprotein (N) and spike (S) recombinant antigens and generation of anti-N and anti-S VHHs for diagnostic and therapeutic applications. SUMMARY We propose a joint effort to generate as […]

Covalent cross-linking combined to mass spectrometry is a powerful approach to address both the structure and composition of protein complexes. To improve the crucial stage of detection and characterization of cross-linked peptides, we have […]

CyaA, a 1706 residue-long protein, is one of the major virulence factors produced by B. pertussis and plays an important role in the early stages of respiratory tract colonization. This toxin uses an original […]

Neurocysticercosis (NCC) caused by Taenia solium, is one of the most important parasitic infections of the central nervous system. Both human and pigs can act as intermediate hosts carrying the larvae stage, i.e. developing […]

  We are developing new computational methods to calculate the electrostatics of proteins, understand their dynamical properties and simulate transitions between two known conformations of the same macromolecule.

EpiK- The Cytosine code as potent target to kill pathogens and fight human diseases Today it is a major health need to find alternatives for increasing antibiotic resistance. Currently there is a large interest […]

We work with archaeal DNA polymerases (PolB) that were evolved to accept xeno-nucleotides to understand the molecular basis of their changed specificity. We use this information to engineer new DNA polymerases to synthesize variants […]

We study the mechanism of DNA Repair of (DNA) Double Strand Breaks  through the so-called Non-Homologous End Joining (NHEJ) process  in mammals using x-ray crystallography and structural studies of pol mu and Tdt

We study the general architecture of the replisome in archaea, especially around the essential PolD, that we discovered to be unique among other DNA polymerases, as it has the fold of multi-subunit RNA polymerases, […]

Rearranged Mixed Lineage lLukaemia (MLLr) is a form of leukaemia representing approximately 75% of paediatric acute leukaemia and 10% of adult leukaemia (AML and ALL), with a very poor prognosis of survival at 5 […]

The European Proteomics Infrastructure Consortium providing access (EPIC-XS) consists of a unified network of experienced access providers and research groups who share a common goal; to facilitate the development and sustainability of proteomics exploration […]

Malaria remains a major global health problem due to the increasing spread of drug resistance and more than 400,000 deaths per year. New drugs that target multidrug resistant parasites are of highest priority. The […]

A Bayesian Framework for Cellular Structural Biology Objective : “The functioning of a single cell or organism is governed by the laws of chemistry and physics. The bridge from biology to chemistry and physics […]

Antimicrobial resistance (AMR) is one of the most pressing global health problems of our times. To counteract AMR, we urgently need new antibiotics, particularly with novel modes of action (MoA). However, while typical antibiotic […]

Expanding the genetic code beyond the A-T/G-C Watson-Crick canonical base pairs and 20 amino acids of natural organisms is a long standing goal in synthetic biology. Reprogrammation of the genetic code can lead to […]

Type IV pili and pseudopili: structure, dynamics, assembly and molecular function Type IV pili and pseudopili assembled by type 2 secretion systems (T2SS) are thin dynamic fibers that perform diverse functions, from  adherence, motility, […]

The FiTeRaD (Field Tests for Rabies Diagnostic) project aims to develop and validate, in laboratory and in the field, the first point of care tests (POCT) for the rapid detection of the etiological agent […]

Synthetic carbohydrate-based conjugates as Shigella vaccine components: design, synthesis, selection and process validation

HDX (Hydrogen Deuterium Exchange) MS is a powerful tool to monitor conformational changes in proteins and to characterize protein-protein interactions. The Synapt G2-Si HDMS mass spectrometer used for HDX experiments is also equipped with […]

Proteins from the hydrophobin family are produced by filamentous fungi in a soluble form, which spontaneously self-assemble at air/water or hydrophobic/hydrophilic interfaces to produce amphipathic layers and accomplish their biological role. Hydrophobin layers consist […]

The availability of recombinant proteins remains a bottleneck for many scientific projects. E.coli is the most widely expression system used, but the production of soluble proteins requires the simultaneous assessment and combination of multiple […]

  A second main line of research of the team is focused on the characterization of protein-protein interactions by exploiting a bacterial two-hybrid screening technology (BACTH) that we have previously developed (Karimova et al., […]

IMPDH from Pseudomonas aeruginosa (see Inosine-5′-monophosphate dehydrogenase project) was found to be allosterically regulated by MgATP (Labesse et al., 2013). The discovery of this mode of regulation of the catalytic activity, never described before […]

NAD mimics as potential antibacterial agents The NAD(P) biosynthesis pathways have attracted recent interest as a source of enzyme targets for the development of antimicrobial agents. Our own research focused on the structure-based development […]

Nucleoside analogues as potential antitumor agents. This project aims to characterize and validate the nucleotide N-hydrolase DNPH1 as a new target in oncology. Inhibition of Rcl alone or in combination with other chemotherapeutic drugs […]

TMPK from Mycobacterium tuberculosis belongs to the NMPK family, which was chosen as potential targets for the development of new antimicrobials (see “Nucleoside monophosphate kinases” project). Based on the 3D-structure of TMPK from M. […]

 Inosine-5′-monophosphate dehydrogenase (IMPDH) is ubiquitously essential for the biosynthesis of guanosine nucleotides and catalyzes the NAD-dependent oxidation of IMP to XMP. IMPDH is a major target in the design of both antitumor and immunosuppresive […]

This project is a part of the international Infect-Era program, AMOEBAC: Entamoeba histolytica-bacterium interaction and the role of this interaction in intestinal pathogenesis (http://www.infect-era.eu/2nd-call-2014) The aim of this investigation is to understand the induced […]

Cryo-EM has greatly expanded our understanding of the structure and function of many important biological systems. The next challenges now concern the responses to the following questions. When advanced classification techniques of single-particle images […]

Our main research projects focus on structural and functional studies of M. tuberculosis DNA gyrase and aim to understand the structural dynamics of DNA recognition by DNA gyrase and the quinolone resistance mechanisms in […]

Affinity Purification Mass Spectrometry (AP-MS) is the method of choice to study protein-protein interactions (PPI) and complexes under near physiological conditions. A protein of interest – the bait – is purified by either a […]

CNF1 is a toxin that catalyzes the permanent activation of host RhoA, Rac1 and Cdc42 small GTPases by selective deamidation of a glutamine residue into a glutamic acid. This 1 dalton post-translational modification can […]

We study the structure and function of ligand-gated ion channels by X-ray crystallography to understand  i) the gating mechanism (opening of the pore upon agonist binding)  ii) the permeation mechanism (transport of ions through […]

Despite the conservation of central metabolism, an increasing amount of evidence indicates that there are unique features in Actinobacteria, one of the largest bacterial phyla that includes important human pathogens like Mycobacterium tuberculosis and […]

Tuberculosis still remains a major threat for public health, with one-third of the world population latently infected, and more than one million deaths per year according to the WHO. Among the factors that have […]

In Escherichia coli and Salmonella enterica serovar Typhimurium, the regulatory protein Crl regulates gene expression by increasing the performance of RpoS/σS sigma factor to modify global gene transcription in stationary phase and under stress […]

Mutations in PDZ Binding Motif (PBM)-containing proteins are also associated to the Usher syndrome, a genetic disease resulting in both hearing loss and visual impairment. Most Usher proteins are present in auditory hair cells […]

  The genes pknA and pknB are located near the origin of replication in M. tuberculosis and are part of a conserved operon that also includes pstP (coding the only known Ser/Thr protein phosphatase […]

Post translational modifications (PTMs) are known to play pivotal roles in cellular physiology and disease, but only a few of the over 300 currently known modifications are extensively investigated in proteomic studies. The most […]

Protein-Protein Interactions (PPIs) are involved in most biological process and diseases. With a recently estimated number of 370,000 PPIs in humans, they constitute a large ‘reservoir’ for therapeutic development compared to ‘conventional’ drug targets. […]

Development of specific imaging nanoprobes against intracerebral targets is a challenging field of research, particularly for the diagnosis of neurodegenerative diseases. Probes based on camelid single-domain antibody-fragments (VHHs or nanobodies) are promising tools due […]

Pathogenic protozoans of the trypanosomatid group still remain a major world health problem. Cycling between insect vectors and mammalian hosts, Trypanosoma cruzi is the causative agent of Chagas disease, while over 20 Leishmania species […]

This PTR aims to gain novel insight into the nature, the expression, and the regulation of Leishmania virulence factors through the investigation of genetics, transcriptomics, and proteomics differences between (i) virulent and avirulent L. […]

Our PTR project investigates at the complex interface between the intracellular pathogen Leishmania and its macrophage host cell. We will apply systems-wide analyses to elucidate the molecular mechanisms underlying the reciprocal metabolic relationship between […]

Within cells, proteins are the real effectors of all activities. The expression of certain proteins changes upon cell stimulation or stress (with virus, inhibitors or bacteria), or when cells differentiate or turn into a […]

  From an applied perspective, we have shown in collaboration with the team of C. Leclerc, (Immune Regulation and Vaccinology, Institut Pasteur) that CyaA can be engineered to serve as a potent non-replicating vector […]

  Other research projects are aimed at exploring the regulatory role of different nucleotides such ppGpp and pppGpp that are both thought to act as second messengers in many complex cellular responses to nutritional […]

Loss of cone photoreceptors in retinitis pigmentosa (RP) leads to complete blindness. The group of Thierry Leveillard at the “Institut de la Vision” showed that injection of the RdCVF protein is a promising therapy […]

Cilia and flagella are essential eukaryotic organelles composed of an evolutionary conserved structure of 9 doublet microtubules that are similar but not equivalent. We propose that a tubulin post-translational modification called glutamylation could act […]

  The CyaA toxin is a 1706 residues-long bifunctional protein (Figure 1): the calmodulin-activated, catalytic domain is located in the 400 amino-proximal residues, whereas the carboxy-terminal 1306 residues are responsible for the binding of […]

Acyl-CoAs are the major metabolic carriers of carbon in living organisms. The most conserved ways to their synthesis include the oxidative decarboxylation of α-ketoacids carried out by three distinct enzymatic machineries: the pyruvate dehydrogenase […]

Protein secretion in bacteria is highly specific. In Gram-negative bacteria, which feature an external (outer) membrane as an additional protective barrier, multiple secretion pathways dedicated to different proteins have been identified. Substrates secreted via […]

Functional nucleic acids (aptamers, DNAzymes, ribozymes, and aptazymes) are generated by in vitro Darwinian evolution methods (SELEX and related methods of in vitro selection). We are interested to expand the capacity of these functional […]

Synthetic peptides and conjugates thereof as potential antivirals (col. H. Lortat-Jacob (CEA, Grenoble), D. Bonnaffé (ICMMO, Orsay) A bi-substrate synthetic glycopeptide resulting from the covalent linkage between a CD4 peptide mimetic and a heparan […]

New TARGETs for osteoporosis: from mesenchymal stem cells to the regulation of osteogenesis and BONE mass.

Malaria is a tropical disease due to a parasite named Plasmodium. It is a global health problem, still causing more than 450.000 deaths each year (mostly African children) and over 200 million infections (http://www.who.int/malaria/en/). […]

An important research axis of the laboratory is to modify nucleic acids with chemical groups in order to improve their therapeutic usefulness. Particularly, modified aptamers (i.e. oligonucleotides capable of binding to targets with high […]

Top-down strategies, based on the study of entire proteins, hold great promise for structural protein analysis. Whilst the classical, bottom-up approach can be useful for locating proteins already deposited in the databases, only a […]

One of the major challenges of modern medicine is to understand how the human organism defends itself against invasions and diseases. The biggest mystery is the human immune system, and understanding this ultimately requires […]

VenoMATIcs’ project aims to strengthen collaborations between Institut Pasteur academic research partners based in 4 MATI regional countries (Morocco, Algeria, Tunisia, Iran), 3 research teams from Institut Pasteur of Paris, in order to use […]

The Innovative Training Network ViBrANT (Viral and Bacterial Adhesin Network Training) brings together world-leading European scientists to train 15 graduate students (early stage researchers) in interdisciplinary research into viral and bacterial adhesins. ViBrANT is […]