Projektbeschreibung
Proteinorganisation zur Organellenbildung: Müssen wir die Geschichte der Biologie neu schreiben?
Man weiß, dass nur durch Bildung von Lipiddoppelschichten eine intrazelluläre Organisation in Organellen möglich ist, mit denen Zellen verschiedene Prozesse auf Bereiche aufteilen können. Doch da es auch membranlose Zellkörperchen wie die Nucleoli gibt, stellt sich die Frage, wie Zellen solche Bereiche abgrenzen und sie davor schützen, mit der Umgebung zu verschmelzen. Das EU-finanzierte Projekt LiquOrg hinterfragt das Konzept, dass membranlose Organellen durch Flüssig-Flüssig-Extraktion gebildet werden. Stattdessen geht es hypothetisch von Flüssigkristallen aus, bei denen sich Oberflächenproteine zu mehreren Schichten organisieren und so die Membranen umgeben und einschließen. Das Forschungsteam wird für den Konzeptnachweis den Golgi-Apparat und dessen Proteine heranziehen.
Ziel
We are in the midst of a revolution in our understanding of the internal organization of cells. In the 1950s we learned that lipid bilayer-based membranes serve as containers (organelles) within the cytoplasm. Now we are learning that liquid-like “membrane-less” organelles i.e. without any container, self-assemble based on “liquid-liquid” phase separations. We propose the seemingly radical idea that membrane-bounded organelles– like their membrane-less counterparts- are stabilized or even templated by analogous phase separations of their surface proteins into largely planar liquids akin to liquid crystals. Our unique Synergy team is organized specifically to test this “liquid crystal hypothesis” on the cell’s secretory compartments - ER exit sites (ERES) and the Golgi stack - by employing our complementary skills in physics, physical chemistry, biochemistry and cell biology. We hypothesize based on pilot experiments evidence that the ERES and Golgi self-organize as a multi-layered series of adherent liquid crystal-like phases of “golgin” and similar proteins which surround and enclose their membranes. Their differential adhesion and repulsion would specify the topology and dynamics of the membrane compartments. If this is true, it will literally rewrite the history of cell biology.
We will test the ‘liquid crystal’ hypothesis directly, systematically, and quantitatively on an unprecedented scale to either modify/disprove it or place it on a firm rigorous footing. Experiments (Aim 1) with 13 pure golgins in cis and trans pairwise combinations will establish their foundational physical chemistry. Surgically engineered changes in golgins/ERES proteins will alter the rank order (hierarchy) of their affinities for each other and link phase separation physics to cell biology (Aim 2) and be used to establish the structural basis of phase separations and their specificity, and the potential for self-assembly of wholly synthetic biological organelles (Aim 3).
Wissenschaftliches Gebiet
Schlüsselbegriffe
Programm/Programme
Thema/Themen
Finanzierungsplan
ERC-SyG - Synergy grantGastgebende Einrichtung
75794 Paris
Frankreich