Project description
Novel biosensors to keep a close watch on neurochemicals
Neurochemical activity is orchestrated by neurotransmitters, neuropeptides and hormones, driving our mental state and behaviour. The scope of the EU-funded OPTONEUROCHEM project is to understand the function of these molecules in health and disease. Towards this goal, researchers will develop genetically encoded sensors for the real-time, high-resolution imaging of neurochemicals. They will study the complex interactions of these molecules and their dynamics in multiple brain regions of awake behaving animals. The generated knowledge will offer unprecedented insight into the field of neurobiology, while the developed tools will transform the current biotechnological landscape.
Objective
How specific neurochemicals (neurotransmitters, neuropeptides and hormones) influence our mental states and behaviors remains one of the biggest questions in biology. So far, we largely lack tools to precisely monitor the temporal and spatial profile of neurochemical signaling in behaving animals. The ability to do this is a prerequisite for understanding the critical functions of these molecules in both health and disease.
OPTONEUROCHEM is a bold and transformative project that will develop a new breed of genetically encoded sensors to enable real-time and highly-specific functional imaging of neurochemicals at unprecedented resolution in awake behaving animals. This project is geared towards creating innovative tools that will transform the current biotechnological landscape.
I will first engineer novel red-shifted sensors for monoamines and apply them in multiplex and optoacoustic imaging experiments (Objective 1). I will then develop sensors for neuropeptides based on previously unexplored receptor subtypes. These will be validated in increasingly complex biological systems and utilized for monitoring the task-specific dynamics of endogenous neuropeptides in multiple brain regions of awake behaving mice (Objective 2). Finally, I will leverage on novel protein scaffolds to engineer the first ultrasensitive probes for steroid hormones and explore their application to in vivo imaging (Objective 3). This high-risk high-reward project combines state-of-the-art cross-disciplinary techniques, ranging from protein engineering and optogenetics, to animal behavior, and in vivo fluorescence and optoacoustic imaging. Together, the next generation tools I plan to develop will revolutionize our approach to study neurochemical activity in living animals. Ultimately, these tools will advance our understanding of brain function in health and disease.
Fields of science
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Funding Scheme
ERC-STG - Starting GrantHost institution
8006 Zurich
Switzerland