Structure and Function of Odorant Binding Proteins and Chemosensory Proteins in Moths.

Odorant Binding Proteins (OBPs) and Chemosensory Proteins (CSPs) are small soluble proteins found in the lymph of insect sensillae located on insect antennae. Odorant Binding proteins are implied in olfaction, by binding hydrophobic odorant molecules and transporting them to the olfactory receptor located on the dendrite of the olfactory neurons. They are divided into three groups, Pheromone Binding Proteins (PBPs), General Odorant Binding Proteins (GOBPs) and Antennal Binding Proteins X (ABPs), and each of them may heve different binding abilities. PBPs and GOBPs are specific of Lepidoptera. Chemosensory Proteins may have the same function of solubilisation and transport of chemosensory molecules. In this thesis, the respective roles of GOBPs and CSPs was investigated using molecular tools. GOBPs from two classes, GOBP1 and GOBP2 were cloned fom two noctuid species, Agrotis ipsilon and Agrotis segetum and their expression within the body and during the development was studied, showing that GOBP2 and GOBP1 are both expressed in male and female antennae, and that GOBP2 is in addition expressed in male legs. Furthermore, GOBP2 is expressed from fifth instar larva to the begining of the pupal stage, whereas GOBP1 expression is restricted to the adult, suggesting a different role for these two classes of proteins that yet remains to be determined. By analysing genome of Bombyx mori, thirteen CSP genes have been discovered. Each of these genes product has a different localization in the insect body, and some of them are expressed in organs not dedicated to chemosensation, suggesting a broader role than chemosensation for these proteins. The B. mori CSP1 protein (BmorCSP1) is mainly expressed in antennae and legs, and could be implied in chemosensation. We therefore determined the three-dimensional structure of the Bombyx mori CSP1 (BmorCSP1) to possibly better understand the function of this protein. BmorCSP1 is an a-helical protein. It has the shape of a prism and an internal cavity that could bind B. mori mori pheromones or given its lmocalisation in antennae and legs, odorant molecules. All data so far obtained for GOBP and CSPs suggest a different role for these two proteins taht yet remains to be determined

Ethnopharmacologie et paludisme au Burkina Faso : sélection de 13 espèces à potentialités antiplasmodiales méconnues

peer reviewedDans la recherche de nouvelles substances actives contre les Plasmodium, les flores non explorées du Sud constituent une source potentielle privilégiée de nouveaux médicaments antipaludéens. Dans ce travail, nous avons suivi une démarche ethnopharmacologique afin de répertorier et de sélectionner des végétaux intéressants à étudier en laboratoire pour leurs propriétés antiplasmodiales. Notre travail de recensement des espèces utilisées contre la malaria au Burkina Faso nous a permis de répertorier 72 espèces végétales utilisées seules ou en association dans le traitement traditionnel du paludisme dans ce pays d’Afrique de l’Ouest. Finalement, treize espèces ont été sélectionnées et dix-sept échantillons végétaux ont été récoltés au Burkina Faso pour évaluation de leurs propriétés antiplasmodiales en laboratoire. Les principaux critères de sélection ont été : leur utilisation traditionnelle contre la malaria et le fait que ces plantes n’aient pas (ou peu) été étudiées sur le plan antiplasmodial. Les liens de chimiotaxonomie éventuels avec des plantes déjà connues pour leurs propriétés antiplasmodiales ainsi que les possibilités de valorisation des espèces au niveau local (MTA) ont également été considérés

Structure of Bombyx mori chemosensory protein 1 in solution

Chemosensory Proteins (CSPs) represent a family of conserved proteins found in insects that may be involved in chemosensory functions. BmorCSP1 is expressed mainly in antennae and legs of the silkworm moth Bombyx morii and was cloned from antennal cDNA. Here we report the determination of the structure of Bombyx mori CSP1 (BmorCSP1) by NMR. The overall fold of BmorCSP1 is globular and comprises six a-helices. These helices span residues 10-14, 17-27, 35-49, 57-72, 75-85, and 92-100. The internal hydrophobic sides of the helices are formed mostly by leucine and isoleucine residues and, therefore, well suited to constitute a binding site for hydrophobic ligands

mHTT Seeding Activity:A Marker of Disease Progression and Neurotoxicity in Models of Huntington's Disease

Self-propagating, amyloidogenic mutant huntingtin (mHTT) aggregates may drive progression of Huntington's disease (HD). Here, we report the development of a FRET-based mHTT aggregate seeding (FRASE) assay that enables the quantification of mHTT seeding activity (HSA) in complex biosamples from HD patients and disease models. Application of the FRASE assay revealed HSA in brain homogenates of presymptomatic HD transgenic and knockin mice and its progressive increase with phenotypic changes, suggesting that HSA quantitatively tracks disease progression. Biochemical investigations of mouse brain homogenates demonstrated that small, rather than large, mHTT structures are responsible for the HSA measured in FRASE assays. Finally, we assessed the neurotoxicity of mHTT seeds in an inducible Drosophila model transgenic for HTTex1. We found a strong correlation between the HSA measured in adult neurons and the increased mortality of transgenic HD flies, indicating that FRASE assays detect disease-relevant, neurotoxic, mHTT structures with severe phenotypic consequences in vivo. Ast et al. present the development of a FRET-based aggregate seeding (FRASE) assay that facilitates the detection and quantification of mHTT seeding activity (HSA) in complex biosamples. They show that HSA is detectable in brains of presymptomatic Huntington's disease (HD) mice and correlates with disease progression and neurotoxicity in HD transgenic flies