The Ebola virus one of the most virulent human pathogens. It induces a generalized haemorrhagic fever with a mortality rate of 25%-90%. Glycoprotein (GP), the unique surface protein and essential for infection, triggers virus attachment to the target cell and viral DNA release into the cytoplasm. The overall objective of this project is to better characterize these viral mechanisms and to obtain neutralizing camelid antibodies targeting key stages of infection. To this end, we will focus our research on obtaining neutralizing antibodies (nanobodies or vHHs) from camelid immunization with the Ebola virus glycoprotein. Nanobodies devoid of light chain have high affinities for their antigens and are easily produced in E. coli. Because infection by Ebola virus is a two-step process, these nanobodies will be assembled in constructions having specificity against the GP in general, for entry into the cell endosome, and against his binding site endosomal fusion site in view to block the release from the endosome. These constructions of neutralizing nanobodies will be tested in vitro and be co-crystallized with the GP in order to improve the binding strength nanobody-GP. Finally, these nanobodies will be used by the partner at the Pasteur Institute to achieve neutralization tests in vitro and by the P4 lab partner in Lyon for mice in vivo tests.

With advancing age, the ability of humans to detect and discriminate odorous molecules declines. Deficits in olfactory function cause a decrease in the quality of life and can affect appetite and thereby impact the nutritional status of elderly individuals. Decreased olfactory function during ageing is paralleled by decreases in other brain functions that occur in the absence of obvious disease states, such as changes in other sensory functions and cognition (memory loss,depression, etc.). Olfactory deficits are also very common in neurodegenerative diseases like Parkinson’s disease and Alzheimer’s disease. These deficits may be partly due to alterations in the maturation of adult-born neurons which incorporate into the neuronal network of the olfactory bulb. We aim to apply cutting-edge technologies to study the basic mechanisms of the survival and maturation of dopaminergic neuronal precursor cells in the olfactory bulb throughout ageing and in Parkinson’s disease. Overall, we seek to establish an in vivo assay that allows the testing of compounds aimed at promoting the maturation of adult-born neurons in altered neuronal networks. Such an assay may not only be relevant for neurodegenerative diseases with early olfactory dysfunction including Alzheimer’s disease and Parkinson’s disease but may also be relevant for other brain diseases of different origin where the integration of adult-born neurons in altered neuronal networks is a potential therapeutical option.