Description du projet
Une étude génomique de la survie à la sécheresse
Dans des conditions extrêmes de sécheresse, un phénomène connu sous le nom de dessiccation, les protéines subissent une agrégation irréversible, menant à la mort cellulaire. Le projet Desiccation Survival, financé par l’UE, examine le rôle des protéines cytosoliques abondantes solubles sous l’effet de la chaleur (CAHS) dans la survie de micro-animaux durant des périodes de sécheresse. Les protéines CAHS sont une famille de protéines intrinsèquement désordonnées (PID) qui subissent une transition vitreuse pour empêcher les protéines intracellulaires de se dérouler. Des chercheurs étudieront les caractéristiques de la séquence nécessaires à cette activité proactive et découvriront de nouvelles séquences susceptibles de sauver les cellules de la dessiccation. Les résultats du projet fourniront des informations importantes sur le mécanisme d’action des PID et proposeront un paradigme pour la conception de biomatériaux innovants.
Objectif
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.
Champ scientifique
Programme(s)
Régime de financement
MSCA-IF-EF-ST - Standard EFCoordinateur
SN2 1FL Swindon
Royaume-Uni