MSc & MSc Funded Theses

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Browsing MSc & MSc Funded Theses by Issue Date

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    An assessment of the suitability of using streptavidin coated microspheres on the test line of a lateral flow immunoassay with a hydrophilic membrane
    (Cranfield University, 2008-09) Warwick, Christopher; Taylor, J.
    Lateral flow immunoassays provide quick, qualitative detection of biomolecules. They are designed to be easy to use, cheap and suitable for applications away from the laboratory. Most lateral flow assays detect a single analyte and use two analyte specific antibodies. One antibody is labelled, and physically separated from the other, which is bound to the test line of a hydrophobic membrane. When a liquid sample is applied, the sample and labelled antibodies flow towards the capture antibodies on the test line. If the analyte is present in the sample, a sandwich assay forms on the test line, giving a visual signal to indicate the presence of the analyte. This research investigated using Streptavidin coated microspheres on the test line of a hydrophilic membrane and a mobile, analyte specific, biotinylated capture antibody upstream of the test line. A hydrophilic membrane material reduced the number of materials required, compared to a traditional design and the Streptavidin provided a method for designing a multi-analyte assay with an analyte independent test line. The mobile biotinylated capture antibody and Streptavidin based test line gave variable results. Only one in four of the target assays developed could detect the analyte used (Rotavirus antigen) and only at higher concentrations, compared to traditional lateral flow designs. Better results were achieved by pre-incubating the biotinylated capture antibody with the Streptavidin microspheres, although it was unable to match the sensitivity of the traditional lateral flow assays. Furthermore, traditional lateral flow designs produced obvious results within ten minutes, while hydrophilic membrane based assays, with Streptavidin test lines, took approximately sixty minutes to produce less distinct signals. Experiments were performed to reduce the time taken to generate signals, but no significant improvement was achieved. Further work should investigate the antibodies, buffers, choice of label, alternative test line capture methods and membrane materials.
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    The application of a decision support system for dispensing practices when purchasing medicines
    (2009-09) Bilbie, Joseph
    In England, Dispensing Practices face the difficulty of purchasing drugs based on clinical need but must strike a balance of retaining cost effectiveness, provide value for money whilst simultaneously maximising profits. The current process of making decisions over where drugs are purchased is very much reliant on buyer intuition and supplier bias rather than extensive knowledge of costs within the supplier market. This feasibility study investigates the theoretical concept of using a decision support system as a best practise approach to identifying the most cost effective sources for Dispensing Practices buying medicines for dispensing. The research was undertaken using a deductive and inductive approach. The inductive approach was carried out in the form of questionnaires and interviews to engage practitioner perspectives. The findings suggest that a decision support system could be used by Dispensing Practices to improve their decisions over where drugs are purchased and used to enable best practise of purchasing medicine. It was proposed that despite some potential weaknesses and concerns regarding reliability it was a concept that could be adopted and utilised as an effective tool to assist healthcare professionals within their role.
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    An examination of knowledge acquisition (KA) requirements and practices within the gas turbine energy industry - does effective KA impact reliability and availability?
    (Cranfield University, 2009-09) Ingham, James; Sehdev, K.
    In order to manage a modern day gas turbine plant, an operator must collect and disseminate a wide range of knowledge, for decision making and for reporting to high level management. Often, an operator must also justify its decisions to a parent company. A key element of power plant management is the use of maintenance strategy, in order to maintain its equipment in an adequate condition so as to reliably produce power when required. This thesis seeks to explore and define the links between effective knowledge management and effective power plant management, which are explored to produce a replicable best practice methodology for a human capital and technology driven KM system in order to enhance operator profitability.
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    An Investigation into the application of Lean Methodology in the UK Hospital Sector
    (Cranfield University, 2009-11) Mistry, Manoj; Wainwright, Charles
    Lean principles have been used in manufacturing organisations globally for many years. Lean principles are increasingly being successfully applied with respect to the delivery of healthcare services on a global scale. Lean begins with eliminating waste, ensuring all work adds value, whilst serving the customer’s / purchaser’s needs. Determining the ‘value added’ and ‘non value’ added steps in every process, is the key tenet of Lean Thinking. For lean principles to be effective, an organisation’s culture that is receptive to its concepts and methodologies is vital. Demonstrated commitment to lean must begin at the very apex of an organisation, and key personnel should be involved in helping to redesign and reshape key processes, with a view to improving flow, whilst at the same time reducing waste. Whilst healthcare differs in many ways from manufacturing, a number of similarities do exist: staff members are dependent on multiple and often complex processes in order to complete their duties, whilst at the same time provide value to the customer or patient. Examples within this Thesis, illustrate Lean principles when applied to a healthcare setting, can have a dramatic effect on cost, productivity, financial performance, and most importantly the timely delivery of services to patients.
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    A systems biology approach to target discovery in regulatory T cells
    (Cranfield University, 2011-08) Weston, Marie C.; Cauchi, Michael; Page, Matt
    Regulatory T cells (Tregs) have a central role in the maintenance of tolerance to self- antigens and the prevention of autoimmune disease. This study used an integrative systems biology approach to identify tolerogenic genes in Tregs which could potentially serve as novel therapeutic targets for immunological disorders. A consensus Treg gene signature was generated by comparing gene expression in Treg vs naïve or conventional T cells across multiple public studies. Ingenuity Pathway Analysis software was then used to expand the Treg consensus gene list to include interacting proteins accessible to intervention by antibody therapeutics. Many viruses co-opt genes for host proteins that modulate the host’s immune system. It is hypothesized that some viruses may have co-opted genes that can induce tolerance, allowing the virus to evade elimination by the host’s immune system. Putative tolerogenic genes were therefore selected for further investigation based upon their presence in viral genomes. The presence of human genes in viral genomes was investigated by performing a batch reciprocal BLAST search. The biological significance of the human vs viral alignments was evaluated by manual inspection of the alignments and searching for the presence of shared motifs and protein family domains in the viral and human sequences. A final list of ten putative tolerogenic genes included genes known to be associated with immune function and some already established therapeutic targets for autoimmune diseases, as well as four potentially novel therapeutic targets. The biological rationale for the putative targets’ involvement in tolerance was explored in the context of Treg gene expression and protein-protein interaction (PPI) network topology. A PPI network was generated and annotated with confidence scores for each of the interactions. The Cytoscape plugin JActiveModules was used to find putative functional network modules.
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    Creation of a software tool for browsing genome variation
    (Cranfield University, 2011-10) Horner, Neil; Larcombe, Lee D; Clark, Taane
    The advent of next generation sequencing has led to an explosion of the amount of DNA sequences in public databases. A challenge is now to find tools that are able to make it easier for researchers to browse and make sense of this data. One organism that has recently been subject to extensive sequencing is Plasmodium falciparum, a devastating pathogen that infects hundreds of millions of people annually. The first goal of this project was to create a new desktop genome variation browser that can quickly handle large amounts of data from sequencing projects involving numerous isolates. The second aim was to use the new tool to analyse recently-sequenced strains of P. falciaprum in order to identify polymorphisms that may be involved in antibiotic resistance. The variation browser described here was written in C++ and the Qt graphical framework in order to make an easy to use and fast tool that can visualise data from variant call format (VCF) files, which is now a de facto standard for storing polymorphism data. The user is able to browse a VCF file to gain a graphical representation of the variation among multiple samples. For rapid identification of relevant polymorphisms, the user is able to filter variant positions using several criteria including mapping quality, sample group membership, and whether the mutations alter the amino acid sequence of a gene. Some basic statistical analysis was incorporated to help identify selective pressures acting on polymorphic sites. The usefulness of the program was ascertained by analysing 75 isolates of P. falciparum from Africa and Asia. Mutations were identified in the chloroquine resistance marker protein, PI4-K, and a putative ubiquitin carboxyl hydrolase, which are potentially involved in antibiotic resistance.
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    Classification of endocrine resistant breast cancers from transcriptomic datasets using multi-gene signatures
    (Cranfield University, 2012-09) Larionov, Alexey; Cameron, David; Morgan, Sarah
    Breast cancer is the most frequent cancer in women in developed countries. Endocrine treatment is indicated to the majority of breast cancer patients. However, in some cases it does not work despite the current clinical indications. Eventually the resistance may develop in many of those who initially respond. Re-analysis of available breast cancer transcriptomic datasets using new multi-gene signatures associated with endocrine resistance may help to understand and overcome endocrine resistance. The goal of this project was to develop a bioinformatics pipeline to (i) select endocrine resistant cases from the available breast cancer datasets and (ii) classify the selected cases by multiple multi-gene signatures. The pipeline has been successfully designed and applied for classification of endocrineresistant samples from 9 breast cancer datasets using 7 transcriptional signatures. The obtained results have been presented in a dedicated web site. The pipeline consists of:  Procedures for a manually curated selection of relevant datasets and signatures;  Procedures for semi-automatic data pre-processing, allowing cross-platform analysis;  A new, fully automated, classification algorithm (Iterative Consensus PAM). The main features of the developed classification algorithm include:  It is based on un-supervised partitioning;  It allows for “non-classifiable” samples;  The procedure does not require a training set;  The procedure can be used in a cross-platform context (Affymetrix & Illumina). The developed pipeline and web site may constitute a prototype for a future web-hub collecting (i) data on endocrine-resistant breast cancer specimens, (ii) collecting multigene signatures relevant to endocrine resistance and (iii) providing tools to apply the signatures to the data. The web-repository could provide a tool to integrate the data and signatures and to produce new clinical and biological knowledge about endocrine resistance in breast cancer.