Projektbeschreibung
Das Genom und das Überleben bei Trockenheit
Unter extremen Trockenheitsbedingungen kommt es zur Austrocknung von Proteinen, die sich dabei unumkehrbar aggregieren und so den Zelltod verursachen. Das EU-finanzierte Projekt Desiccation Survival untersucht nun, welche Rolle CAHS-Proteine (engl. für „im Zytosol häufig vorkommende hitzelösliche Proteine“) für das Überleben von mikroskopisch kleinen Tieren in Trockenphasen spielen. CAHS-Proteine gehören zu den intrinsisch ungeordneten Proteinen (IDP), die intrazelluläre Proteine durch Übergang in einen glasartigen Zustand vor Entfaltung schützen. Das Forschungsteam wird die Sequenzeigenschaften untersuchen, die für diese Schutzmaßnahme nötig sind, und neue Sequenzen ausfindig machen, die Zellen vor Austrocknung schützen können. Aus den Projektergebnissen werden wichtige Erkenntnisse über Wirkmechanismen von IDP sowie ein Paradigma für die Gestaltung innovativer Biomaterialien hervorgehen.
Ziel
Desiccation is a form of stress wherein extremely dry conditions cause intracellular proteins to unfold and aggregate irreversibly, resulting in cell-death. How do cells and organisms survive desiccation is a fundamental question in biology. Cytosolic Abundant Heat Soluble (CAHS) proteins, a family of intrinsically disordered proteins (IDPs) in tardigrades (a phylum of micro-animals), have been shown to be important for their survival during long periods of dryness. Under desiccation condition, CAHS proteins undergo glass-transition and gelation to form vitrified solids that protect intracellular proteins from unfolding and aggregation. However, the features of CAHS proteins that confer protection are unknown. Here, I aim to unravel the sequence determinants of CAHS protein functions, by addressing 3 specific questions:
Aim 1: What are the sequence features that promote glass-transition and gelation in CAHS proteins?
Aim 2: Can we discover new sequences that can rescue cells from desiccation?
Aim 3: What is the sequence-to-function paradigm underlying IDP-mediated desiccation survival?
I will (i) perform computational analysis of existing CAHS proteins to extract their sequence features to design a library for adequate sampling of the sequence space; (ii) screen the library with a high-throughput survival-based assay and validate the hits both in vitro and in vivo; (iii) analyse the results with machine learning algorithms to generate characteristic sequence features underlying protective glass-transition. The learned features will be tested by rationally designing and screening a new sequence library for desiccation survival. This project will provide fundamental sequence-level understanding of how IDPs promote stress response, specifically via glass-transition during desiccation. Moreover, the materials and pipeline generated and the findings of this study will aid in engineering functional biomaterials.
Wissenschaftliches Gebiet
Programm/Programme
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Aufforderung zur Vorschlagseinreichung
Andere Projekte für diesen Aufruf anzeigenFinanzierungsplan
MSCA-IF-EF-ST - Standard EFKoordinator
SN2 1FL Swindon
Vereinigtes Königreich