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Miro dependent mitochondrial dynamics and the regulation of neuronal migration

Objective

Regulated trafficking of mitochondria is essential for providing ATP at the correct spatial location to power neural computation, and for providing Ca2+ buffering at sites of Ca2+ entry or release. In neurons, the concentration of mitochondria in specific regions such as growth cones and synapses is important for correct neuronal function and development. Consequently, defective mitochondrial trafficking is increasingly implicated in neurological diseases. Very little is known regarding the role of mitochondrial positioning and function during neural development such as during the migration of cortical neurons. This proposal will study the mechanisms that control the trafficking of mitochondria in neurons and how this regulates neuronal migration during cortex development. Using imaging, molecular techniques, combined with ex vivo or in utero electroporation and mouse transgenic models I will determine the molecular mechanisms underlying the signalling-dependent positioning of mitochondria in migrating neuronal progenitors. I will examine how the mitochondrial Ca2+-sensing GTPase Miro1 acts as a molecular switch to regulate mitochondrial positioning and function. How Miro1-mediated mitochondrial trafficking regulates neuronal migration in brain development will also be determined. A key goal will be to determine the role of Miro1 Ca2+-sensing and GTPase domains and other components of the Miro1 protein complex including CENPF, DISC1 and Nde1 in the control of mitochondrial positioning in these processes. These studies will significantly advance our understanding of the molecular mechanisms that control mitochondrial signalling-dependent localization in regulating neuronal development. Moreover, understanding these processes may highlight novel therapeutic approaches for neurodevelopmental disorders including Autism Spectrum Disorder, schizophrenia and intellectual disability, where disrupted neuronal migration and cortical wiring are thought to occur.

Fields of science (EuroSciVoc)

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Programme(s)

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Topic(s)

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Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

MSCA-IF-EF-ST - Standard EF

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) H2020-MSCA-IF-2015

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Coordinator

UNIVERSITY COLLEGE LONDON
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 183 454,80
Address
GOWER STREET
WC1E 6BT LONDON
United Kingdom

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Region
London Inner London — West Camden and City of London
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 183 454,80
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