Genetically encoded sensors for imaging neurochemical dynamics in vivo

Descripción del proyecto

Nuevos biosensores para vigilar estrechamente las sustancias neuroquímicas

La actividad neuroquímica está regulada por neurotransmisores, neuropéptidos y hormonas, que dirigen nuestro estado mental y comportamiento. El proyecto financiado con fondos europeos OPTONEUROCHEM tiene por objeto comprender la función de estas moléculas en la salud y la enfermedad. De cara a la consecución de este objetivo, un grupo de investigadores desarrollará sensores codificados genéticamente para la obtención de imágenes de sustancias neuroquímicas en tiempo real y a alta resolución. Estudiarán las interacciones complejas de estas moléculas y su dinámica en múltiples regiones cerebrales de animales en estado de alerta. Los conocimientos obtenidos ofrecerán una información sin precedentes sobre el campo de la neurobiología, mientras que las herramientas desarrolladas transformarán el entorno biotecnológico actual.

Objetivo

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.