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MaCChines SIGNED

Molecular machines based on coiled-coil protein origami

Total Cost €

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EC-Contrib. €

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Partnership

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 MaCChines project word cloud

Explore the words cloud of the MaCChines project. It provides you a very rough idea of what is the project "MaCChines" about.

hydrophobic    single    release    fold    interactions    variants    demonstration    methodology    offers    locomotion    fraction    nature    displacement    modular    molecular    self    flexible    pot    sequence    group    strategies    functional    designed    naturally    coil    science    modules    tetrahedral    dimer    explored    cargo    cc    catalysis    linkers    compact    medicine    prism    2013    branch    polyhedral    introduce    chain    vivo    assembly    contrast    machines    molecules    core    coiled    functions    proteins    nanotweezers    de    unseen    builds    structural    pairwise    structure    disassembly    cages    forming    types    bipyramid    structures    domains    assemble    performing    demonstrated    nanomaterials    protein    regulated    ccpos    origami    caging    construction    pyramid    assembles    tiny    building    strategy    cage    combinatorial    library    rewards    robustness    pioneered    rearrangement    toehold    advantages    frontier    trigonal    shapes    concatenated    throughput    smart    genes    novo    polypeptide    knotted    recognition    positions    positional    sequences    versatile    ccpo    potentials    folds    crosslinked   

Project "MaCChines" data sheet

The following table provides information about the project.

Coordinator
KEMIJSKI INSTITUT 

Organization address
address: HAJDRIHOVA 19
city: LJUBLJANA
postcode: 1000
website: http://www.ki.si

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Slovenia [SI]
 Total cost 2˙497˙125 €
 EC max contribution 2˙497˙125 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2017-ADG
 Funding Scheme ERC-ADG
 Starting year 2018
 Duration (year-month-day) from 2018-09-01   to  2023-08-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    KEMIJSKI INSTITUT SI (LJUBLJANA) coordinator 2˙362˙838.00
2    EN-FIST CENTER ODLICNOSTI SI (LJUBLJANA) participant 134˙286.00

Map

 Project objective

Proteins are the most versatile and complex smart nanomaterials, forming molecular machines and performing numerous functions from structure building, recognition, catalysis to locomotion. Nature however explored only a tiny fraction of possible protein sequences and structures. Design of proteins with new, in nature unseen shapes and features, offers high rewards for medicine, technology and science. In 2013 my group pioneered the design of a new type of modular coiled-coil protein origami (CCPO) folds. This type of de novo designed proteins are defined by the sequence of coiled-coil (CC) dimer-forming modules that are concatenated by flexible linkers into a single polypeptide chain that self-assembles into a polyhedral cage based on pairwise CC interactions. This is in contrast to naturally evolved proteins where their fold is defined by a compact hydrophobic core. We recently demonstrated the robustness of this strategy by the largest de novo designed single chain protein, construction of tetrahedral, pyramid, trigonal prism and bipyramid cages that self-assemble in vivo. This proposal builds on unique advantages of CCPOs and represents a new frontier of this branch of protein design science. I propose to introduce functional domains into selected positions of CCPO cages, implement new types of building modules that will enable regulated CCPO assembly and disassembly, test new strategies of caging and release of cargo molecules for targeted delivery, design knotted and crosslinked protein cages and introduce toehold displacement for the regulated structural rearrangement of CCPOs required for designed molecular machines, which will be demonstrated on protein nanotweezers. Technology for the positional combinatorial library-based single pot assembly of CCPO genes will provide high throughput of CCPO variants. Project will result in new methodology, understanding of potentials of CCPOs for designed molecular machines and in demonstration of different applications.

 Publications

year authors and title journal last update
List of publications.
2020 Tina Lebar, Duško Lainšček, Estera Merljak, Jana Aupič, Roman Jerala
A tunable orthogonal coiled-coil interaction toolbox for engineering mammalian cells
published pages: , ISSN: 1552-4450, DOI: 10.1038/s41589-019-0443-y
Nature Chemical Biology 2020-03-11
2019 Tina Fink, Jan Lonzarić, Arne Praznik, Tjaša Plaper, Estera Merljak, Katja Leben, Nina Jerala, Tina Lebar, Žiga Strmšek, Fabio Lapenta, Mojca Benčina, Roman Jerala
Design of fast proteolysis-based signaling and logic circuits in mammalian cells
published pages: 115-122, ISSN: 1552-4450, DOI: 10.1038/s41589-018-0181-6
Nature Chemical Biology 15/2 2020-03-11

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