Project description
Genomic insight into dryness survival
During extreme conditions of dryness, a phenomenon known as desiccation, proteins undergo irreversible aggregation, leading to cell death. The EU-funded Desiccation Survival project is investigating the role of cytosolic abundant heat soluble (CAHS) proteins in the survival of micro-animals during periods of dryness. CAHS proteins are a family of intrinsically disordered proteins (IDPs) that undergo glass-transition to protect intracellular proteins from unfolding. Researchers will examine the sequence features necessary for this protective activity and discover new sequences that can rescue cells from desiccation. The project's results will provide important knowledge on the mechanism of action of IDPs and offer a paradigm for the design of innovative biomaterials.
Objective
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.
Fields of science
Programme(s)
Funding Scheme
MSCA-IF-EF-ST - Standard EFCoordinator
SN2 1FL Swindon
United Kingdom