GEMiNI · A genetic model for neurorehabilitation
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2018-04-01 → 2020-03-31
- EU contribution
- €160,636
- Participants
- 1
- Scheme
- MSCA-IF-EF-RI
Lines connect the coordinator with its partners.
Results in brief
A genetic model for neurorehabilitation
My long-term objective is to establish the fruit fly Drosophila as a genetic model for neurorehabilitation and recovery after amputation, which will allow the identification of new genes and mechanisms of motor plasticity. In order to carry out these aims, I will take advantage of the sophisticated Drosophila neurogenetic toolkit that allows gene manipulation and the execution of in vivo gain and loss-of-function experiments in a controlled number of neurons. In addition, I will use an adult fly walking assay, the FlyWalker system, which allows a detailed quantification of locomotor activity. Our results show that recovery is a conserved process across species and that age has a deterring effect on this process with older animals lacking the ability to adapt. We also show that genes involved in neuronal plasticity typically associated to olfactory associative memory control the process of recovery. This work will have a significant impact on how we understand motor recovery and will open new venues to promote recovery in motor dysfunction.
Data: CORDIS, © European Union
Project objective
Coordinated walking in vertebrates and multi-legged invertebrates such as the fruit fly Drosophila melanogaster is controlledby an evolutionarily conserved network capable to control movement in a fast, stable, and energy-efficient way. At the sametime, it provides the flexibility to adapt to changes in the terrain, load, and internal motor representations due to disease orinjury. Currently, the contribution of different brain structures responsible for the recovery process is only partially understoodand, importantly, the role of specific genes remains mostly elusive. Preliminary data shows that adult Drosophila flies inwhich the two middle legs were amputated improve their gait performance gradually over the course of a few days engagingin a more controlled gait. We also find that mutants for the learning and memory gene rutabaga lack any kind of short- orlong-term recovery. These results suggest that flies can readjust their motor circuitry upon injury and that a mechanism ofsynaptic plasticity might be involved.The overall goal of this proposal is to establish the fruit fly Drosophila as a genetic model for neurorehabilitation and recoveryafter amputation, which will allow the identification of new genes and mechanisms of motor plasticity. In order to carry outthese aims, I will take advantage of the sophisticated Drosophila neurogenetic toolkit that allows gene manipulation and theexecution of in vivo gain and loss-of-function experiments in a controlled number of neurons. In addition, I will use an adultfly walking assay that I developed during my postdoc, the FlyWalker system, which allows a detailed quantification of locomotor activity. Identifying genes and molecular components that affect the process of plasticity and motor adaptation will allow us to identify new biochemical pathways that influence the recovery process and design new approaches to enhance recovery outcomes.
Original text from CORDIS.
Participants
- UNIVERSIDADE NOVA DE LISBOA · LisboaCoordinatorPortugal
Links
Data: CORDIS, © European Union