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Ca2+ feedback control of TRP/TRPL channels in Drosophila photoreceptors

Objective

A major challenge for any visual system is the dramatic difference in ambient light between a starlit night and midday sun. In contrast to the ciliary rods of vertebrates, the rhabdomeric photoreceptors of the common fruitfly not only reliably detect single photons when dark-adapted (generating responses called ‘quantum bumps’), but continue responding in full daylight. At the core of this performance lie positive and negative feedback loops, many involving Ca2+ entry through the light activated transient receptor potential channels TRP and TRPL. Although Ca2+ modulates virtually every step of the phototransductive cascade, key targets are the channels themselves, leading to: (i) amplification by positive feedback during the rising phase of quantum bumps, (ii) gain reduction by negative feedback during quantum bump termination and during light adaptation. Our objectives are to combine single cell electrophysiology and optogenetics to explore Ca2+ signalling in fly photoreceptors, dissecting both its molecular interaction with TRP and TRPL channels and its dynamics within the cell. Our first aim will be to characterise the role of Calmodulin binding sites and other unknown regulatory sites on TRP and TRPL, in the feedback loops described above. Flies expressing mutated and chimeric TRP/TRPL channels will be used. Our second aim will be to obtain measurements of Ca2+ dynamics with subcellular spatial resolution under physiological illumination. Genetically encoded Ca2+ indicators will be targeted to specific cellular compartments and imaged in intact flies by exploiting the optics of the compound eye. Measurements will be made in fly mutants displaying defective light responses and retinal degeneration, leading to precise hypotheses on the mechanisms responsible for their phenotypes. This project will bring our understanding of rhabdomeric phototransduction to a new level of sophistication, while enriching my professional skills in a world-class laboratory.

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Topic(s)

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Funding Scheme

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MSCA-IF-EF-ST - Standard EF

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Call for proposal

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(opens in new window) H2020-MSCA-IF-2014

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Coordinator

THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
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
TRINITY LANE THE OLD SCHOOLS
CB2 1TN CAMBRIDGE
United Kingdom

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Region
East of England East Anglia Cambridgeshire CC
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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