<p>Technology of today makes it possible to change the way traditional healthcare is conducted. As the population grows older, and the elderly is becoming an increasing part of the whole population, the need for cost efficient and personalised care increases. By implementing home healthcare IT projects, it is possible for more patients to be treated at home with sustained quality of care.</p><p>This thesis documents the work of a master’s degree project carried out during the autumn of 2005. The project is part of a research project within the Department of Biomedical Engineering at Linköping University. The project aims at developing a data model for storing medical data. The model should be general and easy to expand. This model is intended to be used within a larger system allowing a patient to measure medical data from a remote location.</p>

Technology of today makes it possible to change the way traditional healthcare is conducted. As the population grows older, and the elderly is becoming an increasing part of the whole population, the need for cost efficient and personalised care increases. By implementing home healthcare IT projects, it is possible for more patients to be treated at home with sustained quality of care. This thesis documents the work of a master’s degree project carried out during the autumn of 2005. The project is part of a research project within the Department of Biomedical Engineering at Linköping University. The project aims at developing a data model for storing medical data. The model should be general and easy to expand. This model is intended to be used within a larger system allowing a patient to measure medical data from a remote location.

How do microbes adapt to challenges from the environment? In this thesis, two distinct cases were examined through structural and biochemical methods. In the first, we followed a real-time protein evolution of HisA to a novel function. The second case was fusidic acid (FA) resistance mediated by the protein FusB in Staphylococcus aureus. In the first study, the aim was to understand how mutants of HisA from the histidine biosynthetic pathway could evolve a novel TrpF activity and further evolve to generalist or specialist enzymes. We solved the crystal structure of wild type Salmonella enterica HisA in its apo-state and the structures of the mutants D7N and D7N/D176A in complex with the substrate ProFAR. These two distinct complex structures showed us the coupled conformational changes of HisA and ProFAR before catalysis. We also solved crystal structures of ten mutants, some in complex with substrate or product. The structures indicate that bi-functional mutants adopt distinct loop conformations linked to the two functions and that mutations in specialist enzymes favor one of the conformations. We also observed biphasic relationships in which small changes in the activities of low-performance enzymes had large effects on fitness, until a threshold, above which large changes in enzyme performance had little effect on fitness. Fusidic acid blocks protein translation by locking elongation factor G (EF-G) to the ribosome after GTP hydrolysis in elongation and recycling of bacterial protein synthesis. To understand the rescue mechanism, we solved the crystal structure of FusB at 1.6Å resolution. The structure showed that FusB is a two-domain protein and C-terminal domain contains a treble clef zinc finger. Using hybrid constructs between S. aureus EF-G that binds to FusB, and E. coli EF-G that does not, the binding determinants were located to domain IV of EF-G. This was further supported by small-angle X-ray scattering studies of the FusB·EF-G complex. Using single-molecule methods, we observed FusB frequently binding to the ribosome and rescue of FA-inhibited elongation by effects on the non-rotated state ribosome. Ribosome binding of FusB was confirmed by isothermal titration calorimetry.