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Discovery of intrinsically disordered sequences conferring desiccation survival

Periodic Reporting for period 1 - Desiccation Survival (Discovery of intrinsically disordered sequences conferring desiccation survival)

Reporting period: 2019-04-01 to 2021-03-31

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.
Through development of an integrative analytical pipeline, combining computational sequence analysis, structural characterization using NMR, solution biophysics and ensemble generation, membrane biophysics, yeast genetics and cell biology, I successfully identified new protein sequences and features that could contribute to desiccation survival and abiotic stress tolerance in general. I also uncovered the mechanism by which these IDPs achieve stress tolerance.
The results of this project provided insights into how IDPs function in a complex cellular context under stress, and resources to describe functional mechanisms of IDPs across different size and time scales. The project illustrates the importance of studying molecular mechanisms by which abiotic-stress tolerant organisms survive under harsh condition and brings possibility in future bioengineering and fundamental biological research for improving our lives.
An overview of project summary