Desiccation Survival · Discovery of intrinsically disordered sequences conferring desiccation survival
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2019-04-01 → 2021-03-31
- EU contribution
- €212,934
- Participants
- 1
- Scheme
- MSCA-IF-EF-ST
Lines connect the coordinator with its partners.
Results in brief
Discovery of intrinsically disordered sequences conferring desiccation survival
Desiccation is a form of stress wherein extremely dry conditions cause intracellular proteins to unfold and aggregate irreversibly, resulting in cell death. How cells and organisms survive desiccation is a fundamental question in biology. Families of intrinsically disordered proteins (IDPs) in tardigrades (a phylum of microscopic animals), have been shown to be important for their survival during long periods of dryness. Under desiccation conditions, some of these proteins undergo glass-transition and gelation to form vitrified solids that protect intracellular proteins from unfolding and aggregation. However, the features of these proteins that confer protection are unknown. In this project, I endeavoured to unravel how the sequence features of tardigrade disordered proteins dictate their functions in achieving desiccation survival. The results of the project will help us understand better how proteins achieve biological functions and provide insight into possible mechanisms for combating harsh abiotic stresses.
Data: CORDIS, © European Union
Project 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.
Original text from CORDIS.
Participants
- UNITED KINGDOM RESEARCH AND INNOVATION · SWINDONCoordinatorUnited Kingdom
Links
Data: CORDIS, © European Union