"The tsetse fly (Glossina spp.) salivary gland is the final micro-environment where the Trypanosoma brucei parasites adhere and undergo a complex re-programming cycle resulting in an end stage that is re-programmed to continue its life cycle in a new mammalian host. The molecular parasite-vector communications that orchestrate this trypanosome development in tsetse fly salivary glands remain unknown mainly due to the limited availability of experimental tools for functional research. We hypothesize that an innovative paratransgenic approach using the Sodalis glossinidius endosymbiont to deliver Nanobodies that target the trypanosome-tsetse fly crosstalk will open a new avenue to unravel the molecular determinants of this specific parasite-vector association. In this project I will develop an innovative Sodalis-based internal delivery system for Nanobodies to target the tsetse fly – trypanosome interplay and, as final outcome, will generate a trypanosome-resistant tsetse fly. In addition, I will explore the completely ‘unknown’ of the molecular nature of trypanosome adherence to the salivary gland epithelium. This will be addressed by a challenging proteomic-based approach on the tsetse salivary gland - trypanosome membrane complex and by the newly developed paratransgenic approach using the S. glossinidius endosymbiont as an internal delivery system for salivary gland epithelium-targeting Nanobodies. The application of this innovative concept of using pathogen-targeting Nanobodies delivered by insect symbiotic bacteria could be extended to other vector-pathogen systems such as Anopheles gambiae – Plasmodium falciparum and Aedes aegypti – dengue virus."