This project is now closed

Neural circuits controlling brain states and metabolic fluxes

Project supervisor: Denis Burdakov (Neurophysiology)

What logic underlies whole-organism orchestration and health? What components are required (sensors, transistors, logic gates, and predictors)? What are their biological correlates? How do they work together with unity of purpose and without malfunction?

This PhD project will explore these fundamental questions in the context of two processes: brain state regulation and metabolic balance in mammals. These processes are not only of foremost medical relevance (one in four people suffer from obesity and/or insomnia), but importantly, are also amenable to modern tools for observation and manipulation. Unique protein make-up of cells mandatory for normal consciousness and energy balance allows us to target genes and labels to these cells.

The project will involve observing and monitoring genetically-labelled and molecularly-defined circuits inside living brain tissue, for example, the brain orexin/hypocretin circuits, which project both "up" and "down", co-stimulate wakefulness and peripheral glucose fluxes, and protect from narcolepsy and obesity. To establish functional logic of fast interactions between neurons in native circuits, the project will also use optogenetic tools for millisecond control of signals from specific cell types.

The work will involve transgenic mouse models and state-of-the art biological methods including optogenetics, viral gene delivery, electrophysiology, multiphoton imaging, and whole-body metabolic assays. The main focus on functional deconstruction of the brain orexin/hypocretin system, and related “master orchestrator” networks critical for alertness, sleep, and metabolic health.

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