Drivers and consequences of host microbiome control

Projektbeschreibung

Frösche können uns lehren, das Mikrobiom für die Gesundheit nutzbar zu machen

Die Haut beherbergt Mikroben, die vor Infektionen schützen können. Wie aber kontrollieren die Wirte, welche Mikroben bleiben und welche draußen bleiben? Das vom Europäischen Forschungsrat finanzierte Projekt FROGMICRO will diese Frage beantworten, indem es Frösche untersucht, deren Hautmikrobiom ihnen helfen kann, den tödlichen Chytrid-Pilz zu bekämpfen, der die Amphibienpopulationen weltweit ausgerottet hat. Am Beispiel der Geburtshelferkröte werden die Forschenden untersuchen, wie das Immunsystem nützliche Mikroben steuert, wie sich diese Mikroben anpassen und ob die Wirtskontrolle zur Entwicklung natürlicher, übertragbarer mikrobieller Therapien genutzt werden kann. Durch die Verknüpfung von Genomik, Glykomik, Proteomik, KI und Feldforschung könnte FROGMICRO neue Wege zur Entwicklung gesunder Mikrobiome aufzeigen.

Ziel

The epithelial surfaces of animals harbour symbiont communities that influence the health of their hosts, including defending against pathogens. Whilst microbiome effects on host biology have been extensively studied, much less is known about how hosts regulate their microbiomes to ensure that they are pThe epithelial surfaces of animals harbour symbiont communities that influence the health of their hosts, including defending against pathogens. Whilst microbiome effects on host biology have been extensively studied, much less is known about how hosts regulate their microbiomes to ensure that they are populated by beneficial rather than harmful symbionts. The study of host control is critical for both understanding how microbiomes function and for the development of targeted therapies. To meet this need, I will develop an amphibian skin model to ask three key questions exploring host control across major life-stages: 1) How does host control promote symbiont colonization? 2) How does host immune policing and symbiont counter-adaptation shape the microbiome? 3) Can host control be exploited to select transmissible protective microbial therapies? I will examine these questions using the deadly chytrid fungus, Batrachochytrium dendrobatidis (Bd) that is devastating amphibian populations worldwide, and the highly susceptible common midwife toad (Alytes obstetricans), which can be defended by its dermal symbionts. The project has risks, with microbial communities being ecologically complex and fundamental aspects of host biology that are relevant to symbiont control not fully understood. To overcome these challenges, I will apply a combination of novel approaches in glycobiology, proteomics, competition experiments, genomics, in vivo experimentation, AI computer vision and field work. By identifying the major drivers of host control, this project promises to transform our ability to predict microbial community assembly and develop protective symbiont therapies.