13 ERA-CAPS PER-ASPERA Frigerio

The plant endomembrane system underpins virtually every aspect of plant life and feeds every one of us, because it is the 'factory' where proteins and lipids for animal and human nutrition are produced. It is a system of interconnected, membrane-bounded compartments within the cell, forming a metabolic continuum called the secretory pathway. A major component is the endoplasmic reticulum (ER), which is the port of entry of the secretory pathway. The ER is a network of tubular membranes involved in the synthesis, assembly, quality control and export of proteins to other compartments of the secretory pathway. The ER is also a major site for the synthesis of lipids and is present in all eukaryotes, but has unique features in plant cells: it can act as a storage compartment for proteins (like in maize seeds) and lipids (like in oilseed crops such as sunflower). The ER is a very dynamic structure and can change its shape in order to accommodate these diverse functions. However, we do not know why the unique architecture of the ER is necessary for its function. Nothing is known about the factors that regulate plant ER shape and how its shape determines how much protein and lipid the ER can synthesise and/or store.
Over the past 5 years we have made some important discoveries on the mechanisms that may help regulate the organisation of this important structure. We have discovered that a family of proteins called reticulons can induce changes in the shape of the plant ER network, thereby affecting its function. Also we have identified some proteins which are good candidates as regulators of ER network branching, tubule fusions and anchoring. To help our studies, we have contributed to developing a computerised mapping system for analysing the dynamics of the ER.
In essence, we now know the ingredients required to build the architecture of the ER. What we don't yet know is how these ingredients come together to determine it.
In this transnational project, we propose to investigate the nature and interactions of the proteins that anchor the ER network to other organelles, and the proteins that permit new ER tubules to form, to grow and fuse with existing tubules. We will study how changing the expression of these proteins affects the synthesis and transport of lipid storage proteins, especially in cereal seeds. Understanding the function of these key regulators will allow us to redesign the ER in order to improve its capacity to make proteins and lipids in seed crops.

The plant endoplasmic reticulum (ER) is the cellular organelle that regulates the flux of proteins and lipids into the secretory pathway, and is responsible for storing large amount of proteins for human and animal nutrition. The ER has a unique and dynamic architecture, which changes to allow for different biosynthetic functions. Building on our collaborative work over the last 5 years, our team combines expertise in plant molecular and cell biology, biochemistry, microscopy and cereal genetics to bring understanding of ER structure/function relationships to the next level.
We aim at understanding the key molecular determinants of ER shape by studying their function, regulation and interactions. We also propose to investigate interorganellar cooperation by analysing putative contact points between ER and plasma membrane and ER and protein storage vacuoles. We will manipulate the key ER morphogens and assess how changes in ER shape affect protein and lipid biosynthesis and storage. This work will be perfomed in model plants and, importantly, in seeds of cereals (barley, wheat and maize) in order to test directly the ER structure/function relationships in these crop models.

This research combines both basic and translational elements. The importance of the plant secretory pathway in economic terms cannot be understated. A great proportion of the food consumed on the planet in terms of proteins and carbohydrates is manufactured and processed in the organelles of the secretory pathway. Likewise the pathway is responsible for the production of much of the plant extracellular matrix (wall) material which is important in numerous industries (wood, paper etc) and more recently in biofuel production (both in terms of oils and carbohydrates for fermentation). Therefore, any research underpinning our knowledge of the function of the endoplasmic reticulum (ER) has great potential benefit to the development of strategies to manipulate or increase protein productivity in plants. Also the ER is the site of synthesis of many of the economically important molecules that are in development, through plant expression, by the biotechnology sector. Antibodies, peptide antigens and protein based therapeutics being good examples.
Short-to medium term beneficiaries will be applied plant biologists, in particular cereal biologists/breeders. In the long term beneficiaries of this work will include the agricultural sector, through enhanced food production, the biotechnology and health sector through the production of economically valuable molecules and the biofuels sector through oil production in the ER. It is worth noting that Frigerio, Hawes and Stöger have already collaborated in successful projects, such as the EU funded PharmaPlanta programme, on the production of antibodies within the plant ER.
All partner institutions have active technology transfer offices. Therefore, in the event of any exploitable intellectual property emerging from the projects we are well placed for exploitation.