Giuseppe Cammarata. Production and testing of human-derived neurons and brain organoids: advanced model probing in neurodevelopmental disorders

Motivation
Autism and associated neurodevelopmental disabilities are chronic disorders that afflict 1 in 68 children. Not only there is no cure for these conditions but there is also an overall lack of knowledge regarding the precise neurobiological underpinnings leading to synaptic and cellular alterations in human tissue. This project aims to create patient-derived neurons to be used in the understanding of the fundamental characteristics of neurodevelopmental disorders and to identify the neurobiological changes caused by mutations present in autism patients.

Research Challenge
To better understand these disorders, directly accessing neural cells to probe cellular and circuit dysfunctions is both critical and challenging. Current strategies suffer from drawbacks that include heterogeneity in reprogrammed induced pluripotent stem cells and the limited access to biopsies or post-mortem brain samples. Importantly, however, recent evidences have shown that neuronal populations can be differentiated from specific postnatal niches. Dental stem cells are a particularly relevant population since they derive from the neural crest and have been shown to readily differentiate into neurons. As such, there is great potential for the application of dental stem cells in the development of human culture models and cerebral organoids that can provide a breakthrough in understanding disease mechanism.

Brain organoids from dental stem cells offer considerable potential impact as biomedical and biotechnological platform with potential for translational research with personalized medical applications. The usage of dental derived neurons displays potential to dampen the need for animal studies, reduce and contain costs associated with drug development and may provide personalized testing devices with minimally invasive strategies.

The group led by Dr. João Peça at the Center for Neuroscience and Cell biology (CNC), University of Coimbra is focused on understanding neuropsychiatric disorders while dissecting the neuronal circuits controlling behaviors, using a combination of molecular genetics, optogenetics and electrophysiological approaches. It also has proven expertise in the development of novel, genetically engineered mouse models.

Requirements
General Requirements apply.

Supervision and Secondments
The PhD project will be carried out in the Neuronal Circuits and Behavior research group at CNC headed by João Peça. The ESR will enrol in the Doctoral Programme in Experimental Biology and Biomedicine (PDBEB) coordinated by CNC. The project also features secondments (extended stays) at CIP-UEDIN (Peter Kin/Emily Osterweil) and Lundbeck (Niels Plath).

Supervisor(s): João Peça (jpeca@cnc.uc.pt)

Host Location: Center for Neuroscience and Cell biology (CNC), University of Coimbra, Coimbra, Portugal.

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