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From light-stimulated anion receptors to transmembrane carriers and pumps

Description du projet

Transporteurs d’anions transmembranaires, synthétiques et activés par la lumière

Le transport d’anions à travers la membrane cellulaire est essentiel à de nombreux processus biologiques. Le programme de recherche LIGHTPORT, financé par l’UE, vise à développer un système synthétique de récepteurs d’anions dont les propriétés de liaison peuvent être modulées par la lumière et à les utiliser comme transporteurs transmembranaires pour réguler le transport passif et induire le transport actif. Les objectifs du programme comprennent le développement de photocommutateurs actionnés par la lumière visible, le développement de structures mécaniquement imbriquées comme hôtes photocommutables, l’application de ces structures pour le transport par la lumière et le pompage par la lumière d’anions à travers des bicouches phospholipidiques. L’objectif principal est d’utiliser ces travaux pour développer des traitements pharmacologiques localisés basés sur la lumière, tels que l’élimination de cellules cancéreuses ou bactériennes déclenchée par la lumière.

Objectif

The transport of anions across the cell membrane, which is mediated by transport proteins, is essential to many important biological processes. Dysregulation of this transport has been associated to various diseases and therefore, chemists endeavour to develop artificial receptors that mimic the function of natural transporters. Despite much progress over the last decade, the current artificial systems are mostly static, while proteins are able to change their activity dynamically in response to stimuli in the environment. To integrate such stimuli-controlled behavior in synthetic systems is a key contemporary challenge. In view of this, the goal of the proposed research program is to develop anion receptors in which the binding properties can be effectively modulated by light and to apply these receptors as transmembrane carriers and pumps, in order to regulate passive transport (i.e. down a concentration gradient) and to induce active transport (i.e. against a concentration gradient). This interdisciplinary program is divided into three work packages: WP1 aims at the development of structurally rigid and visible-light-actuated photoswitches and their use as platforms for constructing anion receptors; WP2 deals with the development of mechanically interlocked structures as photoswitchable anionic hosts; WP3 is directed at utilizing these receptors for light-gated transport and light-driven pumping of anions across phospholipid bilayers, whereas also an alternative dual-responsive anion channel will be prepared. Eventually, it is expected that this work will open a new route toward light-based localized pharmacological treatment, e.g. via light-triggered cancer or bacterial cell death. Furthermore, active transport systems, that are able to build up and maintain concentration gradients across membranes, could provide a completely new view on how to convert and store light (solar) energy.

Régime de financement

ERC-STG - Starting Grant

Institution d’accueil

UNIVERSITEIT LEIDEN
Contribution nette de l'UE
€ 1 499 461,00
Adresse
RAPENBURG 70
2311 EZ Leiden
Pays-Bas

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Région
West-Nederland Zuid-Holland Agglomeratie Leiden en Bollenstreek
Type d’activité
Higher or Secondary Education Establishments
Liens
Coût total
€ 1 499 461,00

Bénéficiaires (2)