Now showing 1 - 10 of 25
  • Publication
    Research Ready: a student-initiated workshop model for developing foundational research skills
    (American Society for Microbiology, 2023-12)
    Sivarajah, Nivetha
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    Irranious, Jenevan A
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    Krishnamoorthy, Sivagini
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    Kalaineethan, Thayaparan
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    Kugathasan, Deluxeani
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    Sivanantham, Uventhikka
    ;
    ;

    Travel restrictions, pandemics, economic downturn, and increasing costs in organizing workshops all impact on face-to-face training of undergraduates planning to undertake research. The inability to obtain basic, first-hand information regarding research in practice causes undue stress for students and leads to unrealistic expectations regarding research projects. Here, we describe how a student initiated online workshop, co-designed by a group of undergraduate leaders in conjunction with a panel of international academic researchers, and enabled the delivery of an introductory workshop on research training to meet student needs. Post-workshop, over 80%–95% of the participants rated their understanding of different aspects of research in practice as either being good or excellent. The design of this workshop provides an innovative template, in particular for resource-restricted countries, on how student-initiated workshops with multi-institutional academic collaboration could enhance training in research practice.

  • Publication
    Group A streptococcal antigen exposed rat model to investigate neurobehavioral and cardiac complications associated with post-streptococcal autoimmune sequelae
    (John Wiley & Sons, Inc, 2021-06)
    Rafeek, Rukshan A M
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    Lobbe, Catherine M
    ;
    Wilkinson, Ethan C
    ;
    ; ;
    McMillan, David J
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    Sriprakash, Kadaba S
    ;

    Background: The neuropsychiatric disorders due to post-streptococcal autoimmune complications such as Sydenham's chorea (SC) are associated with acute rheumatic fever and rheumatic heart disease (ARF/RHD). An animal model that exhibits characteristics of both cardiac and neurobehavioral defects in ARF/RHD would be an important adjunct for future studies. Since age, gender, strain differences, and genotypes impact on the development of autoimmunity, we investigated the behavior of male and female Wistar and Lewis rat strains in two age cohorts (<6 weeks and >12 weeks) under normal husbandry conditions and following exposure to group A streptococcus (GAS).

    Methods: Standard behavioral assessments were performed to determine the impairments in fine motor control (food manipulation test), gait and balance (beam walking test), and obsessive-compulsive behavior (grooming and marble burying tests). Furthermore, electrocardiography, histology, and behavioral assessments were performed on male and female Lewis rats injected with GAS antigens.

    Results: For control Lewis rats there were no significant age and gender dependent differences in marble burying, food manipulation, beam walking and grooming behaviors. In contrast significant age-dependent differences were observed in Wistar rats in all the behavioral tests except for food manipulation. Therefore, Lewis rats were selected for further experiments to determine the effect of GAS. After exposure to GAS, Lewis rats demonstrated neurobehavioral abnormalities and cardiac pathology akin to SC and ARF/RHD, respectively.

    Conclusion: We have characterised a new model that provides longitudinal stability of age-dependent behavior, to simultaneously investigate both neurobehavioral and cardiac abnormalities associated with post-streptococcal complications.

  • Publication
    Mucosal delivery of ESX-1-expressing BCG strains provides superior immunity against tuberculosis in murine type 2 diabetes
    (National Academy of Sciences, 2020-08-25)
    Sathkumara, Harindra D
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    Muruganandah, Visai
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    Cooper, Martha M
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    Field, Matt A
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    Alim, Md Abdul
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    Brosch, Roland
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    Govan, Brenda
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    Rush, Catherine M
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    Henning, Lars
    ;
    Kupz, Andreas

    Tuberculosis (TB) claims 1.5 million lives per year. This situation is largely due to the low efficacy of the only licensed TB vaccine, Bacillus Calmette-Guérin (BCG) against pulmonary TB. The metabolic disease type 2 diabetes (T2D) is a risk factor for TB and the mechanisms underlying increased TB susceptibility in T2D are not well understood. Furthermore, it is unknown if new TB vaccines will provide protection in the context of T2D. Here we used a diet-induced murine model of T2D to investigate the underlying mechanisms of TB/T2D comorbidity and to evaluate the protective capacity of two experimental TB vaccines in comparison to conventional BCG. Our data reveal a distinct immune dysfunction that is associated with diminished recognition of mycobacterial antigens in T2D. More importantly, we provide compelling evidence that mucosal delivery of recombinant BCG strains expressing the Mycobacterium tuberculosis (Mtb) ESX-1 secretion system (BCG::RD1 and BCG::RD1 ESAT-6 ∆92-95) are safe and confer superior immunity against aerosol Mtb infection in the context of T2D. Our findings suggest that the remarkable anti-TB immunity by these recombinant BCG strains is achieved via augmenting the numbers and functional capacity of antigen presenting cells in the lungs of diabetic mice.

  • Publication
    A murine model of tuberculosis/type 2 diabetes comorbidity for investigating the microbiome, metabolome and associated immune parameters
    (John Wiley & Sons, Inc, 2021-06)
    Sathkumara, Harindra D
    ;
    Eaton, Janet L
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    Field, Matt A
    ;
    Govan, Brenda L
    ;
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    Kupz, Andreas
    Tuberculosis (TB) is one of the deadliest infectious diseases in the world. The metabolic disease type 2 diabetes (T2D) significantly increases the risk of developing active TB. Effective new TB vaccine candidates and novel therapeutic interventions are required to meet the challenges of global TB eradication. Recent evidence suggests that the microbiota plays a significant role in how the host responds to infection, injury and neoplastic changes. Animal models that closely reflect human physiology are crucial in assessing new treatments and to decipher the underlying immunological defects responsible for increased TB susceptibility in comorbid patients. In this study, using a diet-induced murine T2D model that reflects the etiopathogenesis of clinical T2D and increased TB susceptibility, we investigated how the intestinal microbiota may impact the development of T2D, and how the gut microbial composition changes following a very low-dose aerosol infection with Mycobacterium tuberculosis (Mtb). Our data revealed a substantial intestinal microbiota dysbiosis in T2D mice compared to non-diabetic animals. The observed differences were comparable to previous clinical reports in TB patients, in which it was shown that Mtb infection causes rapid loss of microbial diversity. Furthermore, diversity index and principle component analyses demonstrated distinct clustering of Mtb-infected non-diabetic mice vs. Mtb-infected T2D mice. Our findings support a broad applicability of T2D mice as a tractable small animal model for studying distinct immune parameters, microbiota and the immune-metabolome of TB/T2D comorbidity. This model may also enable answers to be found to critical outstanding questions about targeted interventions of the gut microbiota and the gut-lung axis.
  • Publication
    Identification of defective early immune responses to Burkholderia pseudomallei infection in a diet-induced murine model of type 2 diabetes
    (Elsevier Masson, 2021-06)
    Morris, Jodie L
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    Govan, Brenda L
    ;
    Rush, Catherine M
    ;

    Co-occurrence of bacterial infections with type 2 diabetes (T2D) is a global problem. Melioidosis caused by Burkholderia pseudomallei is 10 times more likely to occur in patients with T2D, than in normoglycemic individuals. Using an experimental model of T2D, we observed that greater susceptibility in T2D was due to differences in proportions of infiltrating leucocytes and reduced levels of MCP-1, IFN-γ and IL-12 at sites of infection within 24 h post-infection. However, by 72 h the levels of inflammatory cytokines and bacteria were markedly higher in visceral tissue and blood in T2D mice. In T2D, dysregulated early immune responses are responsible for the greater predisposition to B. pseudomallei infection.

  • Publication
    Requirements for a Robust Animal Model to Investigate the Disease Mechanism of Autoimmune Complications Associated With ARF/RHD
    (Frontiers Research Foundation, 2021-05-05)
    Rafeek, Rukshan A M
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    Sikder, Suchandan
    ;
    ; ;
    McMillan, David J
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    Sriprakash, Kadaba S
    ;
    The pathogenesis of Acute Rheumatic Fever/Rheumatic Heart Disease (ARF/RHD) and associated neurobehavioral complications including Sydenham's chorea (SC) is complex. Disease complications triggered by Group A streptococcal (GAS) infection are confined to human and determining the early events leading to pathology requires a robust animal model that reflects the hallmark features of the disease. However, modeling these conditions in a laboratory animal, of a uniquely human disease is challenging. Animal models including cattle, sheep, pig, dog, cat, guinea pigs rats and mice have been used extensively to dissect molecular mechanisms of the autoimmune inflammatory responses in ARF/RHD. Despite the characteristic limitations of some animal models, several rodent models have significantly contributed to better understanding of the fundamental mechanisms underpinning features of ARF/RHD. In the Lewis rat autoimmune valvulitis model the development of myocarditis and valvulitis with the infiltration of mononuclear cells along with generation of antibodies that cross-react with cardiac tissue proteins following exposure to GAS antigens were found to be similar to ARF/RHD. We have recently shown that Lewis rats injected with recombinant GAS antigens simultaneously developed cardiac and neurobehavioral changes. Since ARF/RHD is multifactorial in origin, an animal model which exhibit the characteristics of several of the cardinal diagnostic criteria observed in ARF/RHD, would be advantageous to determine the early immune responses to facilitate biomarker discovery as well as provide a suitable model to evaluate treatment options, safety and efficacy of vaccine candidates. This review focuses on some of the common small animals and their advantages and limitations.
  • Publication
    Development and characterisation of a laboratory model of post streptococcal autoimmune cardiac and neurobehavioral complications - Dataset

    In this dataset we have provided data on behavioural assessment on rats before and after exposure to streptococcal antigens, histological changes and antibody responses against host tissue proteins. Behavioural tests such as food manipulation, beam walking, grooming, marble burying and light/dark box tests were performed to assess the changes in fine motor coordination, gait and balance, obsessive-compulsive behaviour and anxiety like behaviour respectively before and after exposure to streptococcal antigens. Heart tissues were dissected from rats and stained with haematoxylin and eosin stain and scored them for infiltration of mononuclear cells in the myocardium and valvular tissues. ELISAs were performed on serum collected from rats to assess the antibody response against host tissue proteins following exposure to streptococcal antigens.

  • Publication
    Microbiome-derived metabolome as a potential predictor of response to cancer immunotherapy
    (BMJ Group, 2020-11)
    Malczewski, Agnieszka Beata
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    Navarro, Severine
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    Coward, Jermaine I G
    ;

    Cancer immunotherapy with checkpoint blockade has become standard of care treatment for numerous cancer types. Despite this, robust predictive biomarkers are lacking. There is increasing evidence that the host microbiome is a predictor of immunotherapy response, although the optimal host microbiome has not been defined. Metabolomics is a new area of medicine that aims to analyze the metabolic profile of a biological system. The microbiome-derived metabolome (fecal and serum) represents the end products of microbial metabolism and these may be functionally more important than the distinct bacterial species that comprise a favorable microbiome. Short-chain fatty acids (SCFA) are metabolites produced by gut microbiota and have a role in T cell homeostasis, including differentiation of regulatory T cells. Recent studies have confirmed differential expression of SCFA for immunotherapy responders compared with non-responders. We propose that the microbiome metabolome, with a focus on SCFA may be a novel predictive biomarker for immunotherapy efficacy.

  • Publication
    Q Fever awareness and risk profiles among agricultural show attendees

    Objective: To assess awareness and risk of Q fever among agricultural show attendees.

    Setting: University of New England's Farm of the Future Pavilion, 2019, Sydney Royal Agricultural Show.

    Participants: Participants were ≥18 years, fluent in English, Australian residents, and gave their informed consent.

    Main Outcome Measures: Participants reported whether they had ever heard of Q fever and then completed the ‘Q Tool’ (www.qfevertool.com), which was used to assess participants' demographics and risk profiles. Cross-tabulations and logistic regression analyses were used to examine the relationship between these factors.

    Results: A total of 344 participants were recruited who, in general, lived in major NSW cities and were aged 40–59 years. 62% were aware of Q fever. Living in regional/remote areas and regular contact with livestock, farms, abattoirs and/or feedlots increased the likelihood of Q fever awareness. Direct or indirect contact with feral animals was not associated with Q fever awareness after controlling for the latter risk factors. 40% of participants had a high, 21% a medium, and 30% a low risk of exposure. Slightly less than 10% reported a likely existing immunity or vaccination against Q fever. Among those who were not immune, living in a regional or remote area and Q fever awareness were independently associated with increased likelihood of exposure.

    Conclusions: Awareness of Q fever was relatively high. Although 61% of participants had a moderate to high risk of exposure to Q fever, they had not been vaccinated. This highlights the need to explore barriers to vaccination including accessibility of providers and associated cost.