ALAIN ROUSSEL’S GROUP

The studies we conduct focus on one hand on factors of pathogenicity of bacteria and on the other hand on means of response of host organisms. Our projects can be grouped in 2 scientific disciplines which are immunology and microbiology. 

At the methodological level, X-ray crystallography will remain the basis of all our studies but we are aware of the current developments in the field of structural biology. In particular, the rise of electron microscopy is opening up new avenues. We are also running a camelid antibody generation platform (also called VHH or Nanobody). This tool gives us a significant competitive advantage in tackling most of our projects.

Ebola virus neutralization by camelid nanobodies

Extracellular vesicles covered by recombinant Ebola GP

The project aims at rapidly obtaining novel neutralizing camelid nanobodies against the glycoprotein (GP) from different strains of the Ebola. Camelid nanobodies are immunoglobulin domains that have shown their efficiency in virus neutralization by blocking the attachment of viruses on the host’s receptor. They are easy to produce in Escherichia coli at low costs, and are easily humanized. This research is therefore meant to help developpment of new therapeutic agents for passive immunotherapy against infection by different strains of Ebola virus. Several nanobodies have already been obtained. Biophysical characterization is in progress using extra cellular vesicules covered with Ebola GP.

Cryo-EM tridimensional structure of insect Odorant Receptors

In the context of the development of pest insect biocontrol, odorant receptor proteins are seen as interesting targets to modify insect odorant-guided behaviors. These receptors, expressed in the insect antennae, are indeed determinant for the recognition of volatile molecules. However, the lack of similarity of these receptors with any known membrane protein structure make their study difficult at the molecular level: their tridimensional modelling is impossible; the odorant-binding site cannot be determined. The present project thus proposes to use the more recent developments of atomic resolution cryo-electron microscopy (cryo-EM) to decipher the first tridimensional structures of sex pheromone receptors in complex with their obligatory co-receptor Orco. The cryo-EM structure of homo tetratemer of Orco alone has just been published, but not that of any receptor-Orco complex that may arrange in hetero tetramer. However, this complex is mandatory for pheromone binding. The obtained structures, refined via directed mutagenesis, will serve as matrix to design agonists and/or antagonists to sex pheromones, whose potential in crop protection will be tested on the moth neurons and in fine on the moth behaviour.

Characterization of specific ligand for in situ diagnosis of corneal infections

Ocular surface diseases are a very important part of ophthalmological activity worldwide. All have significant direct or indirect medico-economic repercussions: costly treatments, hospitalizations, corrective surgery, work stoppages, depression, professional incapacity, disability, invalidity, dependency: 285 million people present a serious corneal disease, 10 million of whom are blind, corneal blindness being the third worldwide cause.

Currently, conventional diagnostic methods are insufficient. Indeed, the difficulty of etiological diagnosis causes a delay in management on infectious keratitis (IK), the most frequent corneal disease. They are indirect, long or invasive (painful and/or deleterious on a pathological ocular surface). As bacteria and cells infected by HSV express specific molecules on the ocular surface that will be our targets, the project proposes to solve these major difficulties by developing a new method of minute diagnosis, in vivo and non-invasive based on fluorescent biomarkers (FBM) instilled on the eye and revealed by an ultrasensitive detector. Generation of nanobodies against HSV glycoprotein is in progress.