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How to build a protein factory? Linking structure and function of the plant endoplasmic reticulum

Reference	BB/X006417/1
Principal Investigator / Supervisor	Dr Verena Christine Kriechbaumer
Co-Investigators / Co-Supervisors	Professor John Runions
Institution	Oxford Brookes University
Department	Faculty of Health and Life Sciences
Funding type	Research
Value (£)	400,317
Status	Current
Type	Research Grant
Start date	01/05/2023
End date	30/04/2026
Duration	36 months

Abstract

The plant endoplasmic reticulum (ER) is the first compartment in the secretory pathway and is a major factory for protein and lipid synthesis, quality control, and export. The ER forms a highly dynamic network composed of two morphologically distinct domains: cisternae and tubules. The different morphology types have been suggested to relate to different functional properties but a convincing link has not been established yet. In plants we have two classes of proteins, reticulon and Lunapark proteins that can change the ER network morphology in favour of tubules or cisternae, respectively. Our proposed research aims to link structure and function of the plant ER. We hypothesise that changes in ER structure and dynamics impact on ER functions and productivity focussing on protein production and transport. In particular, we will show that: a) A more cisternal ER structure enhances protein production. b) Changes in ER morphology affect ER to Golgi transport and secretion together with Golgi body morphology. c) ER structural and dynamics changes affect the presence and nature of mini-tubules connecting the ER and Golgi bodies, which we suggest, are important for ER-Golgi transport. To explore this, the project will focus on three key questions: I) The impact of ER structure on protein production II) The impact of ER structure on ER to Golgi protein transport III) The impact of ER structure on secretion This work addresses important cell biological questions but will also be of great importance to the use of plant based expression systems for therapeutics and other high-value products.

Summary

A great proportion of the planet's food supply for proteins and carbohydrates is produced, processed and transported through the plant secretory pathway. The endoplasmic reticulum (ER) forms the first compartment in the secretory pathway and is a major factory for protein and lipid synthesis, assembly, quality control, and export. The ER can also be used to produce molecules important for industry such as antibodies, therapeutics and valuable chemicals. Therefore, biotechnologically the ER has great potential for the development of strategies to manipulate or increase plant productivity. The ER forms a highly dynamic network composed of two morphologically distinct domains: sheets and tubules, which are joined at 3-way junctions to create a loose polygonal structure. The morphology of sheets and tubules has been related to different functional properties. Though both structures are present in all eukaryotic cells, the proportion of each ER structure varies between cells and species which could potentially be linked to the underlying cellular processes and the protein secretion requirements. For example, secretory cells, such as pancreatic and salivary glands, display a higher proportion of sheets. In plants two classes of proteins, reticulon and Lunapark proteins can change the ER network morphology in favour of tubules or sheets, respectively. This project will link structure of the plant ER with ER productivity in terms of protein production and transport. For this, we will change ER structure using ER-shaping proteins and analyse the impact of specific ER structural features such as more tubules or sheets or changes in the movement of the ER on protein production and transport. This is an exciting project as the in-depth knowledge about ER structure and productivity will enable sustainable agricultural production of plants to cater for the planet's increasing food demands and climate change issues. The underlying mechanisms and regulations as well as the possibilities of biotechnological applications of this system will in future inform research areas such as biofuel, plant nutritional composition and pest control, biomarkers and diagnostics.

Committee	Research Committee B (Plants, microbes, food & sustainability)
Research Topics	X – not assigned to a current Research Topic
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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