The development of an effective vaccine against Chlamydia : utilisation of a non-toxic mucosal adjuvant to generate a protective mucosal response

Chlamydia is responsible for a wide range of diseases with enormous global economic and health burden. As the majority of chlamydial infections are asymptomatic, a vaccine has greatest potential to reduce infection and disease prevalence. Protective immunity against Chlamydia requires the induction of a mucosal immune response, ideally, at the multiple sites in the body where an infection can be established. Mucosal immunity is most effectively stimulated by targeting vaccination to the epithelium, which is best accomplished by direct vaccine application to mucosal surfaces rather than by injection. The efficacy of needle-free vaccines however is reliant on a powerful adjuvant to overcome mucosal tolerance. As very few adjuvants have proven able to elicit mucosal immunity without harmful side effects, there is a need to develop non-toxic adjuvants or safer ways to administered pre-existing toxic adjuvants. In the present study we investigated the novel non-toxic mucosal adjuvant CTA1-DD. The immunogenicity of CTA1-DD was compared to our "gold-standard" mucosal adjuvant combination of cholera toxin (CT) and cytosine-phosphate-guanosine oligodeoxynucleotide (CpG-ODN). We also utilised different needle-free immunisation routes, intranasal (IN), sublingual (SL) and transcutaneous (TC), to stimulate the induction of immunity at multiple mucosal surfaces in the body where Chlamydia are known to infect. Moreover, administering each adjuvant by different routes may also limit the toxicity of the CT/CpG adjuvant, currently restricted from use in humans. Mice were immunised with either adjuvant together with the chlamydial major outer membrane protein (MOMP) to evaluate vaccine safety and quantify the induction of antigen-specific mucosal immune responses. The level of protection against infection and disease was also assessed in vaccinated animals following a live genital or respiratory tract infectious challenge. The non-toxic CTA1-DD was found to be safe and immunogenic when delivered via the IN route in mice, inducing a comparable mucosal response and level of protective immunity against chlamydial challenge to its toxic CT/CpG counterpart administered by the same route. The utilisation of different routes of immunisation strongly influenced the distribution of antigen-specific responses to distant mucosal surfaces and also abrogated the toxicity of CT/CpG. The CT/CpG-adjuvanted vaccine was safe when administered by the SL and TC routes and conferred partial immunity against infection and pathology in both challenge models. This protection was attributed to the induction of antigen-specific pro-inflammatory cellular responses in the lymph nodes regional to the site of infection and rather than in the spleen. Development of non-toxic adjuvants and effective ways to reduce the side effects of toxic adjuvants has profound implications for vaccine development, particularly against mucosal pathogens like Chlamydia. Interestingly, we also identified two contrasting vaccines in both infection models capable of preventing infection or pathology exclusively. This indicated that the development of pathology following an infection of vaccinated animals was independent of bacterial load and was instead the result of immunopathology, potentially driven by the adaptive immune response generated following immunisation. While both vaccines expressed high levels of interleukin (IL)-17 cytokines, the pathology protected group displayed significantly reduced expression of corresponding IL-17 receptors and hence an inhibition of signalling. This indicated that the balance of IL-17-mediated responses defines the degree of protection against infection and tissue damage generated following vaccination. This study has enabled us to better understand the immune basis of pathology and protection, necessary to design more effective vaccines.

Plant structure and systematics research at the Queensland University of Technology (QUT), Brisbane

This article provides a general overview of some of the plant research being conducted by a number of researchers at the Queensland University of Technology (QUT) Brisbane. Details about student projects and research facilities have been limited to those of relevance to plant structure and systematics. Academics, technicians and research students involved in plant research are in the Faculty of Science and Engineering, mainly in the School of Earth, Environment and Biological Sciences (EEBS), with a few exceptions. Our offices and laboratories are housed in a number of different buildings at the Gardens Point campus (e.g., P, Q, R, S, M Blocks) and we have strong collaborative links with Queensland Herbarium (BRI) and Mt Coot-tha Botanic Gardens.

Collaborative learning and critical thinking in technology-enhanced environments : an instructional design framework

The nature and characteristics of how learners learn today are changing. As technology use in learning and teaching continues to grow, its integration to facilitate deep learning and critical thinking becomes a primary consideration. The implications for learner use, implementation strategies, design of integration frameworks and evaluation of their effectiveness in learning environments cannot be overlooked. This study specifically looked at the impact that technology-enhanced learning environments have on different learners’ critical thinking in relation to eductive ability, technological self-efficacy, and approaches to learning and motivation in collaborative groups. These were explored within an instructional design framework called CoLeCTTE (collaborative learning and critical thinking in technology-enhanced environments) which was proposed, revised and used across three cases. The field of investigation was restricted to three key questions: 1) Do learner skill bases (learning approach and eductive ability) influence critical thinking within the proposed CoLeCTTE framework? If so, how?; 2) Do learning technologies influence the facilitation of deep learning and critical thinking within the proposed CoLeCTTE framework? If so, how?; and 3) How might learning be designed to facilitate the acquisition of deep learning and critical thinking within a technology-enabled collaborative environment? The rationale, assumptions and method of research for using a mixed method and naturalistic case study approach are discussed; and three cases are explored and analysed. The study was conducted at the tertiary level (undergraduate and postgraduate) where participants were engaged in critical technical discourse within their own disciplines. Group behaviour was observed and coded, attributes or skill bases were measured, and participants interviewed to acquire deeper insights into their experiences. A progressive case study approach was used, allowing case investigation to be implemented in a "ladder-like" manner. Cases 1 and 2 used the proposed CoLeCTTE framework with more in-depth analysis conducted for Case 2 resulting in a revision of the CoLeCTTE framework. Case 3 used the revised CoLeCTTE framework and in-depth analysis was conducted. The findings led to the final version of the framework. In Cases 1, 2 and 3, content analysis of group work was conducted to determine critical thinking performance. Thus, the researcher used three small groups where learner skill bases of eductive ability, technological self-efficacy, and approaches to learning and motivation were measured. Cases 2 and 3 participants were interviewed and observations provided more in-depth analysis. The main outcome of this study is analysis of the nature of critical thinking within collaborative groups and technology-enhanced environments positioned in a theoretical instructional design framework called CoLeCTTE. The findings of the study revealed the importance of the Achieving Motive dimension of a student’s learning approach and how direct intervention and strategies can positively influence critical thinking performance. The findings also identified factors that can adversely affect critical thinking performance and include poor learning skills, frustration, stress and poor self-confidence, prioritisations over learning; and inadequate appropriation of group role and tasks. These findings are set out as instructional design guidelines for the judicious integration of learning technologies into learning and teaching practice for higher education that will support deep learning and critical thinking in collaborative groups. These guidelines are presented in two key areas: technology and tools; and activity design, monitoring, control and feedback.

Essays on technology adoption under uncertainty, globalization and economic growth

This thesis examines how the initial institutional and technological aspects of the economy and the reforms that alter these aspects influence long run growth and development. These issues are addressed in the framework of stochastic endogenous growth models and an empirical framework. The thesis is able to explain why developing nations exhibit diverse growth and inequality patterns. Consequently, the thesis raises a number of policy implications regarding how these nations can improve their economic outcomes.

Consumers' behavioural responses toward technology-based social products

This thesis examined the determinants of consumers’ use of emerging mental health services delivered via mobile phone technology, which promise to provide cost-effective psychotherapeutic support where and when needed. It builds on the Model of Goal-Directed Behaviour by recognising the role that competition between behavioural alternatives plays in influencing consumers’ decision to use these services. The research employed a three-study, mixed-methodological approach.

Hybrid placemaking in the library : designing digital technology to enhance users’ on-site experience

This paper presents research findings and design strategies that illustrate how digital technology can be applied as a tool for hybrid placemaking in ways that would not be possible in purely digital or physical space. Digital technology has revolutionised the way people learn and gather new information. This trend has challenged the role of the library as a physical place, as well as the interplay of digital and physical aspects of the library. The paper provides an overview of how the penetration of digital technology into everyday life has affected the library as a place, both as designed by place makers, and, as perceived by library users. It then identifies a gap in current library research about the use of digital technology as a tool for placemaking, and reports results from a study of Gelatine – a custom built user check-in system that displays real-time user information on a set of public screens. Gelatine and its evaluation at The Edge, at State Library of Queensland illustrates how combining affordances of social, spatial and digital space can improve the connected learning experience among on-site visitors. Future design strategies involving gamifying the user experience in libraries are described based on Gelatine’s infrastructure. The presented design ideas and concepts are relevant for managers and designers of libraries as well as other informal, social learning environments.

Discovering interesting information with advances in web technology

The Web is a steadily evolving resource comprising much more than mere HTML pages. With its ever-growing data sources in a variety of formats, it provides great potential for knowledge discovery. In this article, we shed light on some interesting phenomena of the Web: the deep Web, which surfaces database records as Web pages; the Semantic Web, which de�nes meaningful data exchange formats; XML, which has established itself as a lingua franca for Web data exchange; and domain-speci�c markup languages, which are designed based on XML syntax with the goal of preserving semantics in targeted domains. We detail these four developments in Web technology, and explain how they can be used for data mining. Our goal is to show that all these areas can be as useful for knowledge discovery as the HTML-based part of the Web.

Information skills coursework for postgraduate students : investigation and response at the Queensland University of Technology

In response to current developments In the tertiary education sector, the Queensland University of Technology Library has mounted an Intensive course - Advanced Information Retrieval Skills - for higher degree students. In determining need for such a course, a survey of postgraduate students and their supervisors was conducted. Results of this survey are discussed and details of the four credit point subjects are outlined.

Phenomenography in the Centre for Information Technology Innovation (CITI)

Phenomenography has its roots in educational research (Marton and Booth, 1997), but has since been adopted in other domains including business (Sandberg, 1994), health (Barnard, McCosker and Gerber, 1999), information science (Bruce, 1999a,b) and information technology (Bruce and Pham, 2001) as well as information systems. Emerging phenomenographic research in areas other than education, has been interdisciplinary, often bringing together technology, education and a host discipline such as health or business. In Australia, phenomenography has been used in information technology (IT) related research primarily in Victoria and Queensland. These studies have pursued the latter two of three established lines of phenomenographic research: 1) the study of conceptions of learning; 2) the study of conceptions in specific disciplines of study and 3) the study of how people conceive of various aspects of their everyday world that have not, for them, been the object of formal studies (Marton 1988, p.189). Information Technology researchers have predominantly pursued the latter two lines of research.

Population structure and patterns of genetic variation in a pearl oyster (Pinctada radiata) native to the Arabian Gulf

The study assessed natural levels and patterns of genetic variation in Arabian Gulf populations of a native pearl oyster to define wild population structure considering potential intrinsic and extrinsic factors that could influence any wild structure detected. The study was also the first attempt to develop microsatellite markers and to generate a genome survey sequence (GSS) dataset for the target species using next generation sequencing technology. The partial genome dataset generated has potential biotechnological applications and for pearl oyster farming in the future.

Comparison of genomic DNA extraction techniques from whole blood samples : a time, cost and quality evaluation study

Genomic DNA obtained from patient whole blood samples is a key element for genomic research. Advantages and disadvantages, in terms of time-efficiency, cost-effectiveness and laboratory requirements, of procedures available to isolate nucleic acids need to be considered before choosing any particular method. These characteristics have not been fully evaluated for some laboratory techniques, such as the salting out method for DNA extraction, which has been excluded from comparison in different studies published to date. We compared three different protocols (a traditional salting out method, a modified salting out method and a commercially available kit method) to determine the most cost-effective and time-efficient method to extract DNA. We extracted genomic DNA from whole blood samples obtained from breast cancer patient volunteers and compared the results of the product obtained in terms of quantity (concentration of DNA extracted and DNA obtained per ml of blood used) and quality (260/280 ratio and polymerase chain reaction product amplification) of the obtained yield. On average, all three methods showed no statistically significant differences between the final result, but when we accounted for time and cost derived for each method, they showed very significant differences. The modified salting out method resulted in a seven- and twofold reduction in cost compared to the commercial kit and traditional salting out method, respectively and reduced time from 3 days to 1 hour compared to the traditional salting out method. This highlights a modified salting out method as a suitable choice to be used in laboratories and research centres, particularly when dealing with a large number of samples.

Complete mitochondrial genome sequencing reveals novel haplotypes in a Polynesian population

The high risk of metabolic disease traits in Polynesians may be partly explained by elevated prevalence of genetic variants involved in energy metabolism. The genetics of Polynesian populations has been shaped by island hoping migration events which have possibly favoured thrifty genes. The aim of this study was to sequence the mitochondrial genome in a group of Maoris in an effort to characterise genome variation in this Polynesian population for use in future disease association studies. We sequenced the complete mitochondrial genomes of 20 non-admixed Maori subjects using Affymetrix technology. DNA diversity analyses showed the Maori group exhibited reduced mitochondrial genome diversity compared to other worldwide populations, which is consistent with historical bottleneck and founder effects. Global phylogenetic analysis positioned these Maori subjects specifically within mitochondrial haplogroup - B4a1a1. Interestingly, we identified several novel variants that collectively form new and unique Maori motifs – B4a1a1c, B4a1a1a3 and B4a1a1a5. Compared to ancestral populations we observed an increased frequency of non-synonymous coding variants of several mitochondrial genes in the Maori group, which may be a result of positive selection and/or genetic drift effects. In conclusion, this study reports the first complete mitochondrial genome sequence data for a Maori population. Overall, these new data reveal novel mitochondrial genome signatures in this Polynesian population and enhance the phylogenetic picture of maternal ancestry in Oceania. The increased frequency of several mitochondrial coding variants makes them good candidates for future studies aimed at assessment of metabolic disease risk in Polynesian populations.

A genetic analysis of serotonergic biosynthetic and metabolic enzymes in migraine using a DNA pooling approach

Migraine is a common debilitating primary headache disorder with significant mental, physical and social health implications. The brain neurotransmitter 5-hydroxytryptamine (5-HT; serotonin) is involved in nociceptive pathways and has been implicated in the pathophysiology of migraine. With few genetic studies investigating biosynthetic and metabolic enzymes governing the rate of 5-HT activity and their relationship to migraine, it was the objective of this study to assess genetic variants within the human tryptophan hydroxylase (TPH), amino acid decarboxylase (AADC) and monoamine oxidase A (MAOA) genes in migraine susceptibility. This objective was undertaken using a high-throughput DNA pooling experimental design, which proved to be a very accurate, sensitive and specific method of estimating allele frequencies for single nucleotide polymorphism, insertion deletion and variable number tandem repeat loci. Application of DNA pooling to a wide array of genetic loci provides greater scope in the assessment of population-based genetic association study designs. Despite the application of this high-throughput genotyping method, negative results from the two-stage DNA pooling design used to screen loci within the TPH, AADC and MAOA genes did not support their role in migraine susceptibility.

Molecular cytogenetic analysis of basal cell carcinoma DNA using comparative genomic hybridization

In an attempt to define genomic copy number changes associated with the development of basal cell carcinoma, we investigated 15 sporadic tumors by comparative genomic hybridization. With the incorporation of tissue microdissection and degenerate oligonucleotide primed-polymerase chain reaction we were able to isolate, and then universally amplify, DNA from the tumor type. This combined approach allows the investigation of chromosomal imbalances within a histologically distinct region of tissue. Using comparative genomic hybridization we have observed novel and recurrent chromosomal gains at 6p (47%), 6q (20%), 9p (20%), 7 (13%), and X (13%). In addition comparative genomic hybridization revealed regional loss on 9q in 33% of tested tumors encompassing 9q22.3 to which the putative tumor suppressor gene, Patched, has been mapped. The deletion of Patched has been indicated in the development of hereditary and sporadic basal cell carcinomas. The identification of these recurrent genetic aberrations suggests that basal cell carcinomas may not be as genetically stable as previously thought. Further investigation of these regions may lead to the identification of other genes responsible for basal cell carcinoma formation.