Silicon cell model for the central carbohydrate metabolism of the archaeon Sulfolobus solfataricus under temperature variation (P-N-01-09-23)

This project is part of a large cross-European proposal to investigate what happens to a special type of microorganism when it is grown under different temperatures, using different food sources. We are interested in a microorganism called Sulfolobus solfataricus which is able to survive in extreme conditions such as high temperature (approaching the boiling point of water) and acid conditions. Hence, the interesting question that drives this research is how come it can survive under such extreme conditions, when other microorganisms cannot, and what happens when the conditions change. To investigate how Sulfolobus solfataricus responds to temperature variation, when grown on different types of food (e.g. different types of sugar) we will concentrate on the chemical reactions that occur within the cell. In particular we will concentrate on what is called the central carbohydrate metabolism (CCM) which converts sugar to energy to grow and maintain life via many chemical reactions. During these reactions, proteins are made, modified and broken down. This project, as part of the large EU consortium, which will be conducted in Phillip C Wright's lab in Chemical Engineering at Sheffield, specifically aims to determine when (temporal changes) and by how much these proteins change (quantification and post-translational modification) and whether they interact with each other (protein-protein interactions), under the changing temperatures. The reason this is important is that proteins are the 'doing' molecules in the cells. The results from this programme will feed directly into a wider investigation about how the other parts of the organism work. These other parts include the DNA of the cell and other chemicals that react and move around the cell. The overall idea is to create a computer model that describes how the cell works and how all these chemicals work together to cause the cell to behave how it does. This is important as there is great potential in medicine and biotechnology for proteins that can work in these extreme conditions.

This overall systems biology of microorganisms (SysMO) project will study the central carbohydrate metabolism (CCM) of Sulfolobus solfataricus and its regulation under temperature variation. The archaeal CCM is characterized by unusual pathways and enzymes that often differ from their bacterial or eukaryotic counterparts. Details of regulation and energetic of the CCM will be revealed while we will assemble the data required for integration of genomic, transcriptomic, proteomic, metabolomic, kinetic and biochemical information on the effects of temperature changes. SysMO shall focus on a part of the CCM, i.e. the unusual, branched Entner-Doudoroff (ED) pathway for glucose and galactose uptake and catabolism to pyruvate. The project involves 9 partner laboratories in four countries across Europe. The Sheffield laboratory component revolves around proteomic analysis and resource for the study S. solfataricus under temperature variation. We will implement tools to quantitatively characterize the proteome temporally under temperature and carbon source alteration (type and concentrations). Furthermore, we will also aid in characterization of post-translational modification and protein-protein iterations under these conditions. Finally we will manage the overall '-omics' component of the SysMO S. solfataricus consortium and interface with the overall consortium leaders, and the leaders of the platform modeling programme in particular.