The house mouse (Mus musculus) is among the most abundant synanthropic species and the closest to humans, causing damages and representing a major zoonotic risk. How the house mouse and its zoonotic carriage is influenced by habitat and environment remains however poorly documented. However, the house mouse faces multiple adaptive challenges along the anthropization gradient, from rural to densely populated areas: different exposure to domestic, farmed or wild animal species, greater or lesser exposure to rodenticides, varied anthropic conditions (thermal, dietary, habitat, etc.) and multiple exchanges between populations, influencing their role in the transmission of pathogens. The aim of the project is therefore to integrate approaches from ecology, genomics, evolutionary biology, toxicology, infectiology, and veterinary sciences, to improve the understanding of the house mouse facing the challenge of urbanization, as an element of the biodiversity, as a pest to be managed, and as potential zoonotic vector. The study area will be Lyon (~1.5 million inhabitants) and its surroundings with trappings in the city center, suburbs, periphery, rural landscapes, and expanding cities within a rural matrix, characteristics of the urban sprawl. The project will be organized into work packages aiming to elucidate population structure, the pathogens carried by mice and the adaptive mechanisms developed by the species along the rural/urban gradient, for ultimately proposing management strategies better adapted to local environments. The project will involve three laboratories, LBBE, LEHNA and RS2GP, that have already worked together, bringing all the skills required for the project.

All demographical studies show a constant increase in cancers in the head and neck region, whose annual frequency of new cases is estimated at over 400 000 in the world. In France, the annual incidence of cases of cancer of the lip, oral cavity and pharynx relate to about 15 000 new patients per year. 30 to 40% of these patients (i.e. 4500 and 6000 patients) are treated by radiotherapy (or radiochemotherapy). 90% of them will go on to develop temporary or permanent post-radiation xerostomia (dry-mouth) and/or asialia or hypoasialia (lack or decrease in saliva production). The repercussions can be extremely debilitating, ranging from social embarrassment (slurred speech, prosthetic instability, difficulty in swallowing) to developing serious underlying diseases (sleep disorders, candidiasis and bacterial superinfections, endobuccal chronic caries, extensive dental decay, digestive disturbances, etc.) to a deterioration in the general condition with malnutrition. Currently, treatment of these salivary disorders essentially depends on sialagogue treatment (stimulants of salivary secretion) if the salivary glands are still functional; otherwise, saliva substitutes which are either drugs with a pharmacological effect or products with a physical mechanism, known as medical devices whose purpose is to replace certain physical properties of saliva. These products, which compete with our project, are manual (spray, gels) or external and linked to removable dentures. These devices are restrictive (frequent renewed spraying required) indiscreet (external devices) and/or non-useable (dentures not adapted to the numerous post-surgical situations). Their effectiveness is considered to be moderate. Our project aims to demonstrate the concept of a new implantable medical device for severe salivary secretion caused by head and neck radiation in patients with carcinoma of the head and neck. It will be positioned on hold during surgery for tumour resection in these patients and will then be connected to the motorised module to operate the diffusion of an optimised saliva substitute (if xerostomia is observed), or withdrawn (in the absence of xerostomia). Our project revolves around two parallel and complementary research axes which will involve 1) developing a saliva substitute with rheological, lubrication and wetting properties which are tailored to the pathophysiology of radiation of the oral cavity and 2) to develop an implantable, motorised and autonomous saliva substitute which improves the intraoral distribution of salivary substitutes. Incorporating the container and contents will be validated at a pre-clinical trial in irradiated animals to demonstrate the concept of a new substitute device. The project already involves a business project in the Incubator for Innovative Businesses in Franche-Comté (Cisteo Medical), which is dedicated to the development and manufacturing of new medical devices combining established material, associated motor units, sensors and embedded energy, in partnership with the School of Biomedical Engineers (ISIFC) of the University of Franche-Comté and the University Hospital of Besançon. The further development of the experimental device will be provided later with this future company, once a technology transfer agreement has been established with this company by the valorisation framework of the University of Franche-Comté.