Neuronal Trafficking · Mechanisms of synaptic growth and plasticity
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2016-03-01 → 2018-02-28
- EU contribution
- €160,636
- Participants
- 1
- Scheme
- MSCA-IF-EF-RI
Lines connect the coordinator with its partners.
Results in brief
Mechanisms of synaptic growth and plasticity
Understanding how neurons work is one of the biggest challenges of this century. Neuronal structure and connectivity are genetically determined but can be altered in response to changing levels of activity, a process known as plasticity. Until we understand the biology behind neuronal development and function, it will be difficult to develop informed clinical trials. Defects in synaptic morphology and activity-dependent plasticity are a hallmark of neurodegenerative disorders, which usually involve an initial phase of synapse loss and neuronal simplification, followed by death. A significant problem is that, by the time patients have manifestations of disease, major neuronal cell death has irreversibly occurred, precluding analysis of the processes that led to the loss of neurons - and this, poses a challenge for the development of treatments. My strategy was to use the nervous system of Drosophila. Because 75% of all human disease genes have related sequences in Drosophila, we expect that these studies will contribute to the dissection of the mechanisms that, when disrupted, may lead to disease. My by long-term goal is to understand how neurons grow and remodel. We added two aims to this proposal. Based on these alterations, our objectives are: 1. To dissect the role of Ral/exocyst in postsynaptic growth and activity-dependent plasticity. 2. Regulation of nerve bundle structure and function by Ral GTPase 3. In vivo and in real time mechanisms of synaptic growth 4. To uncover novel regulators of neuronal growth We hope that knowing the basic mechanisms by which neurons acquire their shape and change it in response to activity, and the dissection of the genes that regulate these processes will allow the development of novel therapeutic strategies to delay the progression of neurodegenerative disorders.
Data: CORDIS, © European Union
Project objective
My long-term goal is to understand the cellular and molecular mechanisms that govern synaptic growth and plasticity, and how dysfunction in these pathways contributes to disease. Neurons are the most morphologically diverse cell type whose morphology determines many functional aspects of a neuronal network. The primary shape of a neuron is established during axon and dendrite outgrowth and synapse formation, but is subject to subsequent modifications by physiological events. In response to changes in synaptic activity, neurons can alter both pre and postsynaptic elements of the synapse. Defects in synaptic morphology and in activity-dependent plasticity are a hallmark of several neurodegenerative and cognitive disorders. It is therefore critical to know the basic mechanisms by which neurons acquire their shape and change it in response to activity, and to dissect the genes that regulate these processes. To address these questions, this proposal is divided in the following aims:1) To dissect the postsynaptic role of the Ral/exocyst pathway in synaptic growth and activity-dependent plasticity2) To uncover novel regulators of neuronal membrane trafficking .My strategy is to use the relatively simple nervous system of Drosophila to uncover novel cellular and molecular mechanisms that control synaptic development and plasticity, in order to understand how membrane traffic is regulated to form and modify neuronal structures. Because 75% of all human disease genes have related sequences in Drosophila and nearly a third are predicted to have functionally equivalent counterparts, I expect that these studies in Drosophila will contribute to the dissection of the mechanisms that, when disrupted, may lead to disease. This will help identify points of intervention, therefore directing novel therapies to help curing or ameliorating the symptoms present in many neurological disorders.
Original text from CORDIS.
Participants
- UNIVERSIDADE NOVA DE LISBOA · LisboaCoordinatorPortugal
Links
- View on CORDIS
- DOI: 10.3030/661543
- http://cedoc.unl.pt/neuronal-vision-disorders/
- https://arquivo.pt/wayback/20180410061827/http://cedoc.unl.pt/neuronal-vision-disorders/
Data: CORDIS, © European Union