Research, Innovation and Commercialisation - Research Publications
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ItemBiparatopic nanobodies targeting the receptor binding domain efficiently neutralize SARS-CoV-2(CELL PRESS, 2022-10-20)The development of therapeutics to prevent or treat COVID-19 remains an area of intense focus. Protein biologics, including monoclonal antibodies and nanobodies that neutralize virus, have potential for the treatment of active disease. Here, we have used yeast display of a synthetic nanobody library to isolate nanobodies that bind the receptor-binding domain (RBD) of SARS-CoV-2 and neutralize the virus. We show that combining two clones with distinct binding epitopes within the RBD into a single protein construct to generate biparatopic reagents dramatically enhances their neutralizing capacity. Furthermore, the biparatopic nanobodies exhibit enhanced control over clinically relevant RBD variants that escaped recognition by the individual nanobodies. Structural analysis of biparatopic binding to spike (S) protein revealed a unique binding mode whereby the two nanobody paratopes bridge RBDs encoded by distinct S trimers. Accordingly, biparatopic nanobodies offer a way to rapidly generate powerful viral neutralizers with enhanced ability to control viral escape mutants.
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ItemNo Preview AvailableRising to the challenge of teaching Chinese students( 2020-05-23)
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ItemBasic income: trade-offs and bottom lines(Brotherhood of St Laurence, 2017-11-01)In 2016, Professor Brian Howe, University of Melbourne academic and former Deputy Prime Minister and Minister for Social Security in the Hawke Labor Government, recognised the opportunity to celebrate the 50 plus year legacy of Professor Ronald Henderson, the inaugural director of the Melbourne Institute of Applied Economic and Social Research at the University of Melbourne. Professor Henderson led the National Poverty Inquiry (1972–1975), which resulted in the Henderson Poverty Line as well as a proposal for a Basic Income. The crucial role of social security in mitigating the negative impact of poverty was also considered in the poverty inquiry. Professor Howe, together with Professor Shelley Mallett, General Manager of the Brotherhood of St Laurence’s Research and Policy Centre, and the Melbourne Institute have partnered in a program of activities throughout 2016 and 2017 that honour Professor Henderson’s work on poverty, social security and basic income. This working paper was commissioned by the partners to review existing proposals and trials of basic income and inform discussion of the strengths and weaknesses of basic income approaches, especially in relation to income adequacy. Further papers on basic income will be developed by a range of authors as part of the Henderson Program.
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ItemNo Preview AvailableDiversion Ahead? Change Is Needed but That Doesn’t Mean That Basic Income Is the Answer(Palgrave Macmillan, Cham, 2019)Using an expanded version of De Wispelaere and Stirton’s 2004 framework for assessing basic income policies, we examine selected past and recent trials. The trials have all produced inconclusive results, in part because of the political contexts in which they have been implemented. As a result, they do little to progress policy reforms to address the challenges of economic insecurities and inequalities. Basic income proposals can act as beacons for change, but because they often lack detail, they risk distracting attention from the challenges and opportunities for social security reform. Our expanded framework enables detailed assessment of the dimensions of proposals for change. It also enables the identification of the elements of basic income proposals that can be incorporated into progressive efforts to reclaim social security.
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ItemRecombinant influenza virus expressing HIV-1 p24 capsid protein induces mucosal HIV-specific CD8 T-cell responses(ELSEVIER SCI LTD, 2016-02-24)Influenza viruses are promising mucosal vaccine vectors for HIV but their use has been limited by difficulties in engineering the expression of large amounts of foreign protein. We developed recombinant influenza viruses incorporating the HIV-1 p24 gag capsid into the NS-segment of PR8 (H1N1) and X31 (H3N2) influenza viruses with the use of multiple 2A ribosomal skip sequences. Despite the insertion of a sizable HIV-1 gene into the influenza genome, recombinant viruses were readily rescued to high titers. Intracellular expression of p24 capsid was confirmed by in vitro infection assays. The recombinant influenza viruses were subsequently tested as mucosal vaccines in BALB/c mice. Recombinant viruses were attenuated and safe in immunized mice. Systemic and mucosal HIV-specific CD8 T-cell responses were elicited in mice that were immunized via intranasal route with a prime-boost regimen. Isolated HIV-specific CD8 T-cells displayed polyfunctional cytokine and degranulation profiles. Mice boosted via intravaginal route induced recall responses from the distal lung mucosa and developed heightened HIV-specific CD8 T-cell responses in the vaginal mucosa. These findings demonstrate the potential utility of recombinant influenza viruses as vaccines for mucosal immunity against HIV-1 infection.
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ItemInduction of vaginal-resident HIV-specific CD8 T cells with mucosal prime-boost immunization(NATURE PUBLISHING GROUP, 2018-05-01)Tissue-resident memory (TRM) CD8 T cells survey a range of non-lymphoid mucosal tissues where they rapidly mediate clearance of viral infections at the entry portals. Vaccines that establish CD8 TRM cells in the cervicovaginal mucosa hold promise for effective immunity against sexually transmitted HIV. We demonstrate that HIV-specific CD8 TRM cells can be established in the murine vaginal mucosa using a combined intranasal and intravaginal mucosal immunization with recombinant influenza-HIV vectors. Using in situ tetramer immunofluorescence microscopy, we found that this mucosally administered prime-boost immunization also resulted in the durable seeding of CD8 T cells in the frontline vaginal epithelial compartment as opposed to the vaginal submucosa. Upon cognate antigen recognition within the vaginal mucosa, these HIV-specific CD8 TRM cells rapidly initiated a tissue-wide state of immunity. The activation of HIV-specific CD8 TRM cells resulted in the upregulation of endothelial vessel addressin expression and substantial recruitment of both adaptive and innate immune cells in the vaginal mucosa. These findings suggest that the epithelial localization of HIV-specific CD8 TRM cell populations and their capacity to rapidly activate both arms of the immune system could significantly augment frontline defenses against vaginal HIV infection.
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ItemEffect of cochlear implantation on middle ear function: A three-month prospective study(WILEY, 2018-05-01)OBJECTIVES/HYPOTHESIS: To determine if cochlear implantation has a delayed effect on the middle ear conductive hearing mechanism by measuring laser Doppler vibrometry (LDV) of the tympanic membrane (TM) in both implanted and contralateral control ears preoperatively and 3 months postoperatively, and then comparing the relative change in LDV outcome measures between implanted and control ears. STUDY DESIGN: Prospective cohort study. METHODS: Eleven preoperative adult unilateral cochlear implant recipients in previously unoperated ears with normal anatomy and aerated temporal bones were included in this study. The magnitude and phase angle of umbo velocity transfer function in response to air- conduction (AC) stimulus, and the magnitude of umbo velocity in response to bone- conduction (BC) stimulus were measured in the implant ear and the contralateral control ear preoperatively and 3 months postoperatively and compared. RESULTS: No significant changes in the magnitude or phase angle of TM velocity in response to either AC or BC stimulus were observed in the implanted ear relative to the contralateral control ear 3 months following cochlear implantation. CONCLUSIONS: From the results of LDV measurements, it can be said that cochlear implantation has no significant delayed effect on the middle ear conductive mechanism. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:1207-1212, 2018.
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ItemNovel microsatellite markers suggest the mechanism of parthenogenesis in Extatosoma tiaratum is automixis with terminal fusion(Wiley, 2018-02-01)Parthenogenetic reproduction is taxonomically widespread and occurs through various cytological mechanisms, which have different impact on the genetic variation of the offspring. Extatosoma tiaratum is a facultatively parthenogenetic Australian insect (Phasmatodea), in which females oviposit continuously throughout their adult lifespan irrespective of mating. Fertilized eggs produce sons and daughters through sexual reproduction and unfertilized eggs produce female offspring via parthenogenesis. Here, we developed novel microsatellite markers for E. tiaratum and characterized them by genotyping individuals from a natural population. We then used the microsatellite markers to infer the cytological mechanism of parthenogenesis in this species. We found evidence suggesting parthenogenesis in E. tiaratum occurs through automixis with terminal fusion, resulting in substantial loss of microsatellite heterozygosity in the offspring. Loss of microsatellite heterozygosity may be associated with loss of heterozygosity in fitness related loci. The mechanism of parthenogenetic reproduction can therefore affect fitness outcomes and needs to be considered when comparing costs and benefits of sex versus parthenogenesis.
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ItemAntifogging Surface Facilitated by Nanoscale Coatings with Controllable Hydrophobicity and Cross-Linking Density(WILEY-V C H VERLAG GMBH, 2017-01-01)