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Synthetic Cell Biology: Designing organelle transport mechanisms

Description du projet

DEENESFRITPL

Conception de vésicules synthétiques dans les cellules vivantes

Les cellules abritent un réseau complexe d’organites et de vésicules membranaires qui assurent la synthèse, la transformation et le transport de macromolécules telles que les protéines et les lipides destinées à être sécrétées ou utilisées à l’intérieur de la cellule. Ce réseau joue un rôle crucial dans divers processus cellulaires, notamment la sécrétion d’hormones et le maintien de l’homéostasie cellulaire. Financé par le Conseil européen de la recherche, le projet ArtifiCell se concentre sur la conception de nouveaux mécanismes de transport de vésicules dans les cellules vivantes. Les chercheurs souhaitent concevoir la machinerie protéique centrale impliquée dans la formation, le ciblage et la fusion des vésicules. Pour ce faire, ils concevront des vésicules synthétiques à base de phospholipides et des acides nucléiques peptidiques afin de rediriger les vésicules sécrétoires vers des cibles spécifiques.

Objectif

Imagine being able to design into living cells and organisms de novo vesicle transport mechanisms that do not naturally exist? At one level this is a wild-eyed notion of synthetic biology.
But we contend that this vision can be approached even today, focusing first on the process of exocytosis, a fundamental process that impacts almost every area of physiology. Enough has now been learned about the natural core machinery (as recognized by the award of the 2013 Nobel Prize in Physiology or Medicine to the PI and others) to take highly innovative physics/engineering- and DNA-based approaches to design synthetic versions of the secretory apparatus that could someday open new avenues in genetic medicine.
The central idea is to introduce DNA-based functional equivalents of the core protein machinery that naturally form (coats), target (tethers), and fuse (SNAREs) vesicles. We have already taken first steps by using DNA origami-based templates to produce synthetic phospholipid vesicles and complementary DNA-based tethers to specifically capture these DNA-templated vesicles on targeted bilayers. Others have linked DNA oligonucleotides to trigger vesicle fusion.
The next and much more challenging step is to introduce such processes into living cells. We hope to break this barrier, and in the process start a new field of research into “synthetic exocytosis”, by introducing Peptide-Nucleic Acids (PNAs) of tethers and SNAREs to re-direct naturally-produced secretory vesicles to artificially-programmed targets and provide artificially-programmed regulation. PNAs are chosen mainly because they lack the negatively charged phosphate backbones of DNA, and therefore are more readily delivered into the cell across the plasma membrane. Future steps, would include producing the transport vesicles synthetically within the cell by externally supplied origami-based PNA or similar cages, and - much more speculatively - ultimately using encoded DNA and RNAs to provide these functions.

Champ scientifique

Programme(s)

Thème(s)

Appel à propositions

ERC-2014-ADG

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Régime de financement

ERC-ADG - Advanced Grant

Institution d’accueil

UNIVERSITY COLLEGE LONDON
Contribution nette de l'UE
€ 2 200 000,00
Adresse
GOWER STREET
WC1E 6BT London
Royaume-Uni

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Région
London Inner London — West Camden and City of London
Type d’activité
Higher or Secondary Education Establishments
Liens
Coût total
€ 2 200 000,00

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Dernière mise à jour: 8 Juin 2022

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Permalink: https://cordis.europa.eu/project/id/669612/fr

European Union, 2024