Understanding the regulation of polyglucan biosynthesis in eukaryotic cells

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Carbon storage in living cells is essential for the fitness and survival of organisms. In particular, glucose (Glc), stored as polyglucans such as starch in plants and glycogen in many other organisms, serve crucial roles throughout their respective life cycles. Starch is a water insoluble polyglucan synthesized inside plastids of higher plants acting as a short- and long-term energy store, whereas glycogen is water-soluble, acting as a readily accessible major reserve carbohydrate in yeasts and animals. Starch is one of the most important agricultural commodities in the world, and the major determinant of yield in domesticated cereals and grasses, whose starchy endosperms provide the bulk of caloric intake of humans and livestock. The coordination and cooperation of enzyme activities involved in starch biosynthesis is beginning to be understood. My laboratory has studied the regulation of this important pathway for more than 15 years, applying biochemistry, molecular biology, bioinformatics, plant physiology and cell biology to understand its role in determining starch structure and yield. We have shown that protein-protein interactions and protein phosphorylation play important roles in the post-translational control of starch synthesis by regulating many enzyme activities, as well as controlling assembly and disassembly of specific protein complexes. In addition to the core biosynthetic pathway, many auxiliary components, including essential non-catalytic proteins e.g. 14-3-3s (eukaryotic proteins which regulate protein-protein interactions), protein kinases and phosphatases are responsible for regulating starch synthesis. Many enzymes of glycogen metabolism are regulated by protein phosphorylation, but in contrast to the situation in plants, almost nothing is known of protein-protein interactions between the enzymes of glycogen synthesis. The broad goal of my research program is to further understand the post translational control of starch biosynthesis in plants and glycogen synthesis in yeast. By studying the two related systems of carbon storage we will gain valuable insight into parallel modes of post-translational control of these two important pathways. Over the next five years, I will address gaps in our knowledge in key areas of the pathway of storage starch deposition in cereal endosperms, the control of starch synthesis inside plastids, and the regulation of glycogen biosynthesis. Specifically, I will investigate the post-translational regulation of 1) pathways of sucrose metabolism and formation of the precursor for starch synthesis, ADPGlc, in the cytoplasm of cereal endosperm 2) plastidial ADPGlc synthesis, and 3) investigate parallel regulatory systems in yeast by analyzing the protein-protein interactome involved in key stages of glycogen formation. Understanding the regulatory systems controlling cellular carbon storage represents an important contribution to knowledge with applications in agriculture and mammalian health.