School of Biomedical Sciences - Research Publications

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    The eyes have it: dim-light activity is associated with the morphology of eyes but not antennae across insect orders
    Freelance, CB ; Tierney, SM ; Rodriguez, J ; Stuart-Fox, DM ; Wong, BBM ; Elgar, MA (OXFORD UNIV PRESS, 2021-10)
    Abstract The perception of cues and signals in visual, olfactory and auditory modalities underpins all animal interactions and provides crucial fitness-related information. Sensory organ morphology is under strong selection to optimize detection of salient cues and signals in a given signalling environment, the most well-studied example being selection on eye design in different photic environments. Many dim-light active species have larger compound eyes relative to body size, but little is known about differences in non-visual sensory organ morphology between diurnal and dim-light active insects. Here, we compare the micromorphology of the compound eyes (visual receptors) and antennae (olfactory and mechanical receptors) in representative pairs of day active and dim-light active species spanning multiple taxonomic orders of insects. We find that dim-light activity is associated with larger compound eye ommatidia and larger overall eye surface area across taxonomic orders but find no evidence that morphological adaptations that enhance the sensitivity of the eye in dim-light active insects are accompanied by morphological traits of the antennae that may increase sensitivity to olfactory, chemical or physical stimuli. This suggests that the ecology and natural history of species is a stronger driver of sensory organ morphology than is selection for complementary investment between sensory modalities.
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    Hypnotics with novel modes of action
    Hoyer, D ; Allen, A ; Jacobson, LH (WILEY, 2020-02)
    Insomnia and, more generally, lack of sleep are on the rise. Traditionally treated by classical hypnotics, such as benzodiazepines and Z drugs, which both act on the GABAA receptor, and other modalities, including nondrug therapies, such as cognitive behavioural therapy, there is a range of new hypnotics which are being developed or have recently received market approval. Suvorexant and the like target the orexin/hypocretin system: they should have less side effects in terms of drug-drug interactions with e.g. alcohol, less memory impairment and dependence potential compared to classical hypnotics.
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    The Salmonella Effector SseK3 Targets Small Rab GTPases
    Gan, J ; Scott, NE ; Newson, JPM ; Wibawa, RR ; Wong Fok Lung, T ; Pollock, GL ; Ng, GZ ; van Driel, I ; Pearson, JS ; Hartland, EL ; Giogha, C (FRONTIERS MEDIA SA, 2020-08-19)
    During infection, Salmonella species inject multiple type III secretion system (T3SS) effector proteins into host cells that mediate invasion and subsequent intracellular replication. At early stages of infection, Salmonella exploits key regulators of host intracellular vesicle transport, including the small GTPases Rab5 and Rab7, to subvert host endocytic vesicle trafficking and establish the Salmonella-containing vacuole (SCV). At later stages of intracellular replication, interactions of the SCV with Rab GTPases are less well defined. Here we report that Rab1, Rab5, and Rab11 are modified at later stages of Salmonella infection by SseK3, an arginine N-acetylglucosamine (GlcNAc) transferase effector translocated via the Salmonella pathogenicity island 2 (SPI-2) type III secretion system. SseK3 modified arginines at positions 74, 82, and 111 within Rab1 and this modification occurred independently of Rab1 nucleotide binding. SseK3 exhibited Golgi localization that was independent of its glycosyltransferase activity but Arg-GlcNAc transferase activity was required for inhibition of alkaline phosphatase secretion in transfected cells. While SseK3 had a modest effect on SEAP secretion during infection of HeLa229 cells, inhibition of IL-1 and GM-CSF cytokine secretion was only observed upon over-expression of SseK3 during infection of RAW264.7 cells. Our results suggest that, in addition to targeting death receptor signaling, SseK3 may contribute to Salmonella infection by interfering with the activity of key Rab GTPases.
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    High antibody titres induced by protein subunit vaccines using Mycobacterium ulcerans antigens Hsp18 and MUL _3720 with a TLR-2 agonist fail to protect against Buruli ulcer in mice
    Mangas, KM ; Tobias, NJ ; Marion, E ; Babonneau, J ; Marsollier, L ; Porter, JL ; Pidot, SJ ; Wong, CY ; Jackson, DC ; Chua, BY ; Stinear, TP (PEERJ INC, 2020-08-07)
    BACKGROUND: Mycobacterium ulcerans is the causative agent of a debilitating skin and soft tissue infection known as Buruli ulcer (BU). There is no vaccine against BU. The purpose of this study was to investigate the vaccine potential of two previously described immunogenic M. ulcerans proteins, MUL_3720 and Hsp18, using a mouse tail infection model of BU. METHODS: Recombinant versions of the two proteins were each electrostatically coupled with a previously described lipopeptide adjuvant. Seven C57BL/6 and seven BALB/c mice were vaccinated and boosted with each of the formulations. Vaccinated mice were then challenged with M. ulcerans via subcutaneous tail inoculation. Vaccine performance was assessed by time-to-ulceration compared to unvaccinated mice. RESULTS: The MUL_3720 and Hsp18 vaccines induced high titres of antigen-specific antibodies that were predominately subtype IgG1. However, all mice developed ulcers by day-40 post-M. ulcerans challenge. No significant difference was observed in the time-to-onset of ulceration between the experimental vaccine groups and unvaccinated animals. CONCLUSIONS: These data align with previous vaccine experiments using Hsp18 and MUL_3720 that indicated these proteins may not be appropriate vaccine antigens. This work highlights the need to explore alternative vaccine targets and different approaches to understand the role antibodies might play in controlling BU.