Descripción del proyecto
Datos genómicos sobre la capacidad de supervivencia a la sequedad
En condiciones de sequedad extrema, un fenómeno conocido como desecación, las proteínas experimentan una agregación irreversible que conduce a la muerte celular. El proyecto financiado con fondos europeos Desiccation Survival está investigando la función de las proteínas citosólicas abundantes solubles en calor en la supervivencia de microanimales durante períodos de sequedad. Se trata de una familia de proteínas intrínsecamente desordenadas (PID) que sufren una transición vítrea para proteger las proteínas intracelulares contra el despliegue. Los investigadores estudiarán las características de las secuencias necesarias para que se produzca esta actividad protectora con el fin de descubrir nuevas secuencias que puedan salvar a las células de la desecación. Los resultados del proyecto proporcionarán importantes conocimientos sobre el mecanismo de acción de las PID y un paradigma para el diseño de biomateriales innovadores.
Objetivo
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.
Ámbito científico
Programa(s)
Régimen de financiación
MSCA-IF-EF-ST - Standard EFCoordinador
SN2 1FL Swindon
Reino Unido