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Genetic dissection of a tonically active neural circuit

Objective

Understanding how the brain works is a fundamental challenge in biology and a priority of EU research. A subset of brain circuits can signal tonically to encode persistent stimuli. Such circuits are involved in many sensory systems (e.g. vision, hearing) and in homeostatic responses (e.g. temperature, pH, and posture control). How tonic activity is molecularly achieved remains poorly understood. In C. elegans a tonic circuit promotes aggregation behavior and escape from 21% oxygen. At its core this circuit comprises URX oxygen sensors that tonically stimulate RMG interneurons as oxygen approaches 21%, evoking a switch in behavioral state. Each neuron in the circuit can be imaged and selectively modified in vivo - providing a special opportunity to dissect a tonically active circuit. Genetic screens have isolated 74 mutants with behavioral defects linked to URX-RMG tonic activity and that appear to disrupt hitherto unstudied loci. I am currently identifying the genes defective in these mutants, something I expect to achieve by May 2016 when the Fellowship would begin. I propose to combine genetics, neural imaging, optogenetics and biochemistry to characterize these genes’ function. I expect to define groups of gene products that act together. Some will be hitherto uncharacterized in any animal. I propose to collaborate with partners in the host institute and elsewhere to characterize the function of conserved genetic pathways I discover in depth. I will gain added value from learning new approaches (e.g. biochemistry, CLEM, cell-specific RNA Seq) and by extending some of my findings into a vertebrate model. I expect my research to provide general insights into molecular mechanisms by which tonic circuits work, with potential implications for human disease. This project is likely to pioneer new lines of research indispensible to establish an independent research career, will broaden and deepen my technical expertise, and will help me develop new scientific networks.

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Keywords

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Programme(s)

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Topic(s)

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Funding Scheme

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MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)

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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

UNITED KINGDOM RESEARCH AND INNOVATION
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
POLARIS HOUSE NORTH STAR AVENUE
SN2 1FL Swindon
United Kingdom

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Region
South West (England) Gloucestershire, Wiltshire and Bristol/Bath area Swindon
Activity type
Research Organisations
Links
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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