A thesis submitted to the Faculty of Science, University of the Witwatersrand, Johannesburg in fulfilment of the requirements for the degree of Doctor of Philosophy. June 2017, Johannesburg / As sequencing and genotyping technologies are advancing, larger and more complex sets of biological data are being produced. Databases can be used to efficiently store and manage the data. Typically, publicly available datasets are accessed through web browsers that offer a user-friendly interface to a database, making complex queries simple to execute. However, research projectspecific data are not commonly stored in this way. In this research, a database (designed in MySQL) and accompanying interface (developed using PHP, HTML and CSS) has been designed for the storage and querying of the quality controlled data from the current project using Metabochip-genotyped Birth to Twenty (Bt20) cohort participants and their female caregivers. Users can easily access the data to generate summary statistics on the phenotype data and download phenotype, single nucleotide polymorphism (SNP) annotation and association analysis data that match user-supplied criteria. Some of the data from the database was used to investigate the genetics of blood pressure (BP) in black South African individuals. Hypertension is a major risk factor for cardiovascular diseases (CVDs). BP variation is known to have a genetic component, but genetic studies in indigenous Africans have been limited. Association analysis, carried out in a merged sample of caregivers and participants, pointed to novel regions of interest in the NOS1AP (DBP and SBP), MYRF (SBP) and POC1B (SBP) genes and two intergenic regions (DACH1|LOC440145 (DBP and SBP) and INTS10|LPL (SBP)). Two SNPs in the MYRF gene met the calculated “array-wide” significance threshold (p<6.7x10-7 for the merged dataset) for multiple testing. Genotype imputation is a useful addition to association studies to increase the SNP panel for association testing. An investigation into the efficiency of imputation in this dataset using a mixed population reference panel was carried out. Imputation was achieved with high confidence in all genes, but a more detailed view of the region was only seen in NOS1AP (DBP and SBP in both the merged and female caregiver datasets) and POC1B (Bt20 participant dataset only). Overall, the research contributed a useful tool for the efficient management of project-specific biological data. The analysis and genotype imputation, which is a promising tool in future studies in this or other African datasets, also provided some insight into the genetics of blood pressure in black South Africans with further functional and replication studies in larger samples required to confirm and explain the findings. / MT 2017

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published_or_final_version / Computer Science and Information Systems / Master / Master of Philosophy

1 v. (various paging) : ill., tables, diags ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.)--University of Adelaide, Dept. of Computing Science, 1976

Thesis (MSc (Biochemistry))--University of Stellenbosch, 2007. / A detailed mathematical description of all the processes in a cell could be an informative tool for investigating biological function. Detailed kinetic models could be built either by obtaining enzyme kinetic parameters in vitro, or by obtaining them from time series analyses of metabolite data from rapid pulse experiments. A genome scale in vitro enzyme kinetic assay project would be prohibitively laborious with the current technologies. Further, there are still uncertainties about the importance of in vivo effects such as metabolite channelling, spatial effects and molecular crowding which could make in vitro determined parameters invalid. Accordingly, there is much interest in in vivo experiments for kinetic modelling. In vivo experimental methods suffer from a number of technical and even fundamental problems. Technical problems are being solved by more sensitive metabolomics tools and rapid sampling technologies. However, the large number of effectors of each enzyme reaction makes it impossible to obtain models at the level of detail possible with the in vitro method. Ultimately, the solution to building a genome scale Silicon Cell is to make use of both strategies. As metabolomics technologies are rapidly improving, it would thus make sense to follow the parts-based in vitro kinetics methodology, and carry out a detailed accuracy assessment of the model with in vivo experiments. To address the problem of the fundamental limit of information from concentration time-series, other in vivo experiments will have to be carried out as well. 13C-metabolic flux analysis has recently undergone vast improvements with the use of better experimental protocols and powerful algorithms for flux calculation. Incorporation of this type of experiment in the validation protocol is the aim of this thesis, which represents an intermediary step towards using the genome-scale stoichiometric models as platforms for building genome-scale kinetic models. It is illustrated here how kinetic models can be combined with metabolic flux data in a special way which allows correct modelling of boundary conditions and validation using novel concepts. We used 13C-metabolic flux analysis and gas chromatography-mass-spectrometry to measure metabolic fluxes through the central metabolic pathways of the yeast Saccharomyces cerevisiae. This data was integrated with a previously constructed detailed kinetic model of fermentative glycolysis in the yeast to illustrate our approach. Various implications for such data integration with kinetic models were identified and a software program was designed for this purpose.

A research report submitted to the Faculty of Science, University of the Witwatersrand, Johannesburg, in partial fulfilment of the requirements of the degree of Master of Science. Johannesburg 2014 / Field trips to museums have been shown to achieve important learning outcomes and promote scientific literacy. However, the success of museum visits relies, in part, in the ability of teachers to effectively mediate the museum experience. A critical analysis of the literature on teacher-led field trips has shown that they are not always conducted in optimal ways and the use of worksheets is a good illustration of this dilemma. Characteristics of effective museum worksheets are described in best-practice literature; however there is a mismatch between researcher recommendations and teacher practices. Clearly there exists a need to improve teacher practice in informal educational settings. This study sought to provide insight on the ability of a teacher to follow recommendations outlined by the literature and create a best-practice worksheet. It involved two visits to the Johannesburg Zoo, with two different groups of Grade eight learners, where they were observed and audio-recorded whilst completing one of two museum worksheets. The first worksheet was designed before the teacher was aware of best-practice recommendations. The second worksheet attempted to improve on the first using researcher recommendations. The worksheets were analysed, using a worksheet analysing instrument, which showed that both contained more factors that would hinder learning and few factors that would facilitate learning. These findings suggest that, even with knowledge of best-practice recommendations, the teacher was not able to construct a worksheet that completely facilitated free-choice learning – barriers to the process included: the context of the zoo i.e. the plethora of information boards that rendered most observation-dependent questions as text-dependent; the tendency of the teacher to take advantage of the zoo setting and therefore the use of questions with a high site specificity; an increased use of orientation cues needed to reduce the ‘novelty factor’; and the use of the worksheet as an assessment tool that, therefore, provided little choice in where and how learners applied tasks asked of them. The study also investigated insight on whether or not the worksheets promoted curriculum related conversations among a group of learners. Learner conversations were coded, focusing on both nature of discourse as well as type of discourse, and analysis showed that learners cognitively and affectively engaged with worksheet tasks. However, the nature of cognitive engagement tended to be on a superficial level, suggesting learners do not have the necessary ii skills - e.g. language, argumentation and critical analysis - to initiate and conduct exploratory discussions. In view of these findings, it was concluded that it is difficult to translate best-practice recommendations into actual field trip experiences. The agenda of the teacher as well as the ability of his or her learners strongly influence how a worksheet is conducted and the worksheet is used.

published_or_final_version / abstract / toc / Computer Science and Information Systems / Master / Master of Philosophy

published_or_final_version / Zoology / Master / Master of Philosophy

No description available.