Characterization of the neuromodulatory network orchestrating hunger-dependent behavioral and physiological plasticity in Drosophila

• Applicant: Privatdozent Dr. Meet Zandawala
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells ; Animal Physiology and Biochemistry
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 507904410

Neuropeptides and peptide hormones (hereafter referred to as NPHs) are the largest class of neuronal signaling molecules that allow animals to flexibly adapt their behavior and physiology to varying environmental conditions and internal states. Functional studies on NPH signaling have revealed that most NPHs are pleiotropic. Furthermore, multiple NPHs can influence a given behavior. But how multiple NPH signaling pathways interact to orchestrate organismal behavior and physiology under a given context are poorly understood. Moreover, resolving the spatial and temporal dynamics of NPH signaling (what are the targets of NPHs, when are they modulated and for how long?) has also been challenging due to a lack of tools to observe neuromodulatory activity in-vivo. Hence, the aim of this project is to decipher the NPH signaling network and the signaling dynamics which mediate hunger-dependent behavioral and physiological plasticity in Drosophila. We will use glucose homeostasis and its related internal feeding-state (low glucose = hungry vs high glucose = satiated) as a well-characterized experimental system to address this aim across three work packages. This is an ideal system to decipher neural correlates of context-dependent plasticity because (1) we know the specific nutrient-sensing neurons involved in this process and have genetic access to them, (2) several signaling pathways and mechanisms are conserved across the animal kingdom and, importantly, (3) robust behavioral and physiological assays are available as readouts to monitor glucose imbalance. In addition, we have recently refined and improved a powerful genetic tool, TANGO-Map, to analyze paracrine or hormonal signaling in-vivo. The outcomes of this project will thus be crucial in understanding how NPHs link the internal feeding state of the animal to different behavioral outcomes. We will also unravel the complex modulatory interactions between different NPH signaling pathways as well as the significance of these interactions to the metabolic homeostasis and the overall well-being of the animal. Moreover, by visualizing the dynamics of NPH signaling using TANGO-Map, we will discover fundamental principles of neuromodulatory signaling which will be an important step towards decoding the functioning of the brain. Ultimately, this technique will set the foundation to broadly examine dysregulated hormonal signaling which is a hallmark of several human disorders like obesity, depression and sleep disorders.

• DFG Programme: Research Grants