Plants, being sessile organisms, must sense and respond to environmental change, such as temperature or drought, without being able to move. Evolution has led to a diverse array of detection, signalling and mitigation responses, and understanding how these functions and can be manipulated is a crucial factor for maintaining food security in response to climate change.
Osmolarity Induced Ca2+ (OSCA) ion channels are conserved across eukaryotes (TMEM63 family; Murthy et al., 2018. eLife 7:e41844) and are used by plants to detect and respond to changes in osmotic potential. OSCA channels are thought to do this by detecting changes in membrane tension and rigidity (Douget & Honoré. 2019. Cell 179(2): 340-354). However, no mechanism underlying this hypothesised mode of action has been identified. We recently discovered that many OSCA ion channels are subject to a poorly understood type of post-translational modification called S-acylation. S-acylation involves the addition of long chain fatty acids to cysteine residues in proteins and acts to promote interaction of proteins, or domains of proteins, with membranes. S-acylation is unique amongst lipid modifications of proteins in that it is reversible; this allows it to regulate function in a similar way to phosphorylation or ubiquitination. S-acylation would provide an ideal mechanism for OSCA channels to detect changes in membrane tension, rigidity and fluidity. We have since demonstrated that OSCA channels are some of the most dynamically S-acylated proteins within the plant cell, indicating that OSCA channel function is regulated at some level by S-acylation.
This project aims to elucidate how S-acylation affects OSCA channel outputs in plants, how OSCA S-acylation is regulated and the mechanisms by which S-acylation affects OSCA channel function to provide greater insight into how plants mitigate against environmental stress. This will be done using an interdisciplinary approach, combining methods in laboratory-based plant physiology, molecular biology, S-acylation assays, chemical biology, calcium imaging and biochemistry with in silico structural biology and molecular dynamics simulations. The specific approaches used will be dictated by the abilities, desires and interests of the student.