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Dr Michael Liu

Biography

I hold a Bachelor degree from the University of New South Wales (2006) and subsequently a PhD in Microbiology (2012). From 2006-2008 I worked as a Scientist at the biotech company Biosignal Pty Ltd. In 2008 I returned to academia as a PhD candidate within the Centre for Marine Bio-Innovation (CMB) at UNSW and received a scholarship (APAI) from the Australia Research Council in 2008. I went on to carry out postdoctoral research at the ithree Institute within the University of Technology Sydney in 2012 and took on a research associate position in 2014.

Professional

I currently operate the Sequencing Core Facility at the UTS’s ithree Institute. The main purpose of which is to provide high-level technical support to strengthen and centralize resources around a research area within the UTS research community. The Core is equipped with the knowledge, expertise and instrumentation to perform high-throughput whole genome sequencing analysis, integerated metagenomics/microbiomics data production and analysis. In addition, the Core Facility has built relationships with other institutions and research groups to gain access to instrumentation and expertise with the focus to develop community outreach encouraging metagenomics/microbiomics; establish multidisciplinary consultative microbiomic resources and; to facilitate public/private collaborative microbiomics in Sydney Australia.
Image of Michael Liu
Research Associate, The ithree Institute
Core Member, ithree - Institute of Infection, Immunity and Innovation
BSc (HONS 1) (UNSW), Grad Cert Sc (UNSW), PhD (UNSW)
 
Phone
+61 2 9514 1601

Research Interests

My research focuses on the interaction of bacteria with their environment and aims to better understand human-microbial interactions and how that can be used to improve human health in various ways. This includes the development of integrated multi-‘omics’ approach to aid in biological interpretation and bioinformatics method for data process. In addition, we are interested in how the human microbiome is altered by various environmental stimuli such as age, diet, and exercise, and the implications of these on various diseases and therapeutic treatments.

Journal articles

Liu, M., Lu, J., Muller, P., Turnbull, L., Burke, C.M., Schlothauer, R.C., Carter, D.A., Whitchurch, C.B. & Harry, E.J. 2015, 'Antibiotic-specific differences in the response of Staphylococcus aureus to treatment with antimicrobials combined with manuka honey', Frontiers in Microbiology, vol. 6, no. JAN.
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Skin infections caused by antibiotic resistant Staphylococcus aureus are a significant health problem worldwide; often associated with high treatment cost and mortality rate. Complex natural products like New Zealand (NZ) manuka honey have been revisited and studied extensively as an alternative to antibiotics due to their potent broad-spectrum antimicrobial activity, and the inability to isolate honey-resistant S. aureus. Previous studies showing synergistic effects between manuka-type honeys and antibiotics have been demonstrated against the growth of one methicillin-resistant S. aureus (MRSA) strain. We have previously demonstrated strong synergistic activity between NZ manuka-type honey and rifampicin against growth and biofilm formation of multiple S. arueus strains. Here, we have expanded our investigation using multiple S. aureus strains and four different antibiotics commonly used to treat S. aureus-related skin infections: rifampicin, oxacillin, gentamicin, and clindamycin. Using checkerboard microdilution and agar diffusion assays with S. aureus strains including clinical isolates and MRSA we demonstrate that manuka-type honey combined with these four antibiotics frequently produces a synergistic effect. In some cases when synergism was not observed, there was a significant enhancement in antibiotic susceptibility. Some strains that were highly resistant to an antibiotic when present alone become sensitive to clinically achievable concentrations when combined with honey. However, not all of the S. aureus strains tested responded in the same way to these combinational treatments. Our findings support the use of NZ manuka-type honeys in clinical treatment against S. aureus-related infections and extend their potential use as an antibiotic adjuvant in combinational therapy. Our data also suggest that manuka-type honeys may not work as antibiotic adjuvants for all strains of S. aureus, and this may help determine the mechanistic processes behind honey syner...
Liu, M., Lu, J., Muller, P., Turnbull, L., Burke, C.M., Schlothauer, R.C., Carter, D.A., Whitchurch, C.B. & Harry, E.J. 2015, 'Antibiotic-specific differences in the response of Staphylococcus aureus to treatment with antimicrobials combined with manuka honey', Frontiers in Microbiology, vol. 6, no. JAN.
View/Download from: UTS OPUS or Publisher's site
Skin infections caused by antibiotic resistant Staphylococcus aureus are a significant health problem worldwide; often associated with high treatment cost and mortality rate. Complex natural products like New Zealand (NZ) manuka honey have been revisited and studied extensively as an alternative to antibiotics due to their potent broad-spectrum antimicrobial activity, and the inability to isolate honey-resistant S. aureus. Previous studies showing synergistic effects between manuka-type honeys and antibiotics have been demonstrated against the growth of one methicillin-resistant S. aureus (MRSA) strain. We have previously demonstrated strong synergistic activity between NZ manuka-type honey and rifampicin against growth and biofilm formation of multiple S. arueus strains. Here, we have expanded our investigation using multiple S. aureus strains and four different antibiotics commonly used to treat S. aureus-related skin infections: rifampicin, oxacillin, gentamicin, and clindamycin. Using checkerboard microdilution and agar diffusion assays with S. aureus strains including clinical isolates and MRSA we demonstrate that manuka-type honey combined with these four antibiotics frequently produces a synergistic effect. In some cases when synergism was not observed, there was a significant enhancement in antibiotic susceptibility. Some strains that were highly resistant to an antibiotic when present alone become sensitive to clinically achievable concentrations when combined with honey. However, not all of the S. aureus strains tested responded in the same way to these combinational treatments. Our findings support the use of NZ manuka-type honeys in clinical treatment against S. aureus-related infections and extend their potential use as an antibiotic adjuvant in combinational therapy. Our data also suggest that manuka-type honeys may not work as antibiotic adjuvants for all strains of S. aureus, and this may help determine the mechanistic processes behind honey syner...
Liu, M. & Darling, A. 2015, 'Metagenomic Chromosome Conformation Capture (3C): techniques, applications, and challenges.', F1000Research, vol. 4, p. 1377.
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We review currently available technologies for deconvoluting metagenomic data into individual genomes that represent populations, strains, or genotypes present in the community. An evaluation of chromosome conformation capture (3C) and related techniques in the context of metagenomics is presented, using mock microbial communities as a reference. We provide the first independent reproduction of the metagenomic 3C technique described last year, propose some simple improvements to that protocol, and compare the quality of the data with that provided by the more complex Hi-C protocol.
Lu, J., Turnbull, L., Burke, C.M., Liu, M.Y., Carter, D.A., Schlothauer, R.C., Whitchurch, C.B. & Harry, L. 2014, 'Manuka-type honeys can eradicate biofilms produced by Staphylococcus aureus strains with different biofilm-forming abilities', PeerJ, vol. 2.
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Chronic wounds are a major global health problem. Their management is difficult and costly, and the development of antibiotic resistance by both planktonic and biofilm-associated bacteria necessitates the use of alternative wound treatments. Honey is now being revisited as an alternative treatment due to its broad-spectrum antibacterial activity and the inability of bacteria to develop resistance to it. Many previous antibacterial studies have used honeys that are not well characterized, even in terms of quantifying the levels of the major antibacterial components present, making it difficult to build an evidence base for the efficacy of honey as an antibiofilm agent in chronic wound treatment. Here we show that a range of well-characterized New Zealand manuka-type honeys, in which two principle antibacterial components, methylglyoxal and hydrogen peroxide, were quantified, can eradicate biofilms of a range of Staphylococcus aureus strains that differ widely in their biofilm-forming abilities. Using crystal violet and viability assays, along with confocal laser scanning imaging, we demonstrate that in all S. aureus strains, including methicillin-resistant strains, the manuka-type honeys showed significantly higher anti-biofilm activity than clover honey and an isotonic sugar solution. We observed higher anti-biofilm activity as the proportion of manuka-derived honey, and thus methylglyoxal, in a honey blend increased. However, methylglyoxal on its own, or with sugar, was not able to effectively eradicate S. aureus biofilms. We also demonstrate that honey was able to penetrate through the biofilm matrix and kill the embedded cells in some cases. As has been reported for antibiotics, sub-inhibitory concentrations of honey improved biofilm formation by some S. aureus strains, however, biofilm cell suspensions recovered after honey treatment did not develop resistance towards manuka-type honeys. New Zealand manuka-type honeys, at the concentrations they can be applie...
Yin, Z., Wang, Y., Whittell, L.R., Jergic, S., Liu, M., Harry, E., Dixon, N.E., Kelso, M.J., Beck, J.L. & Oakley, A.J. 2014, 'DNA replication is the target for the antibacterial effects of nonsteroidal anti-inflammatory drugs.', Chemistry & biology, vol. 21, no. 4, pp. 481-487.
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Evidence suggests that some nonsteroidal anti-inflammatory drugs (NSAIDs) possess antibacterial properties with an unknown mechanism. We describe the in vitro antibacterial properties of the NSAIDs carprofen, bromfenac, and vedaprofen, and show that these NSAIDs inhibit the Escherichia coli DNA polymerase III subunit, an essential interaction hub that acts as a mobile tether on DNA for many essential partner proteins in DNA replication and repair. Crystal structures show that the three NSAIDs bind to the sliding clamp at a common binding site required for partner binding. Inhibition of interaction of the clamp loader and/or the replicative polymerase subunit with the sliding clamp is demonstrated using an in vitro DNA replication assay. NSAIDs thus present promising lead scaffolds for novel antibacterial agents targeting the sliding clamp.
Yin, Z., Whittell, L.R., Wang, Y., Jergic, S., Liu, M., Harry, E.J., Dixon, N.E., Beck, J.L., Kelso, M.J. & Oakley, A.J. 2014, 'Discovery of Lead Compounds Targeting the Bacterial Sliding Clamp Using a Fragment-Based Approach', Journal of Medicinal Chemistry, vol. 57, no. 6, pp. 2799-2806.
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Nguyen, M.T., Liu, M. & Thomas, T. 2014, 'Ankyrin-repeat proteins from sponge symbionts modulate amoebal phagocytosis.', Molecular ecology, vol. 23, no. 6, pp. 1635-1645.
Bacteria-eukaryote symbiosis occurs in all stages of evolution, from simple amoebae to mammals, and from facultative to obligate associations. Sponges are ancient metazoans that form intimate symbiotic interactions with complex communities of bacteria. The basic nutritional requirements of the sponge are in part satisfied by the phagocytosis of bacterial food particles from the surrounding water. How bacterial symbionts, which are permanently associated with the sponge, survive in the presence of phagocytic cells is largely unknown. Here, we present the discovery of a genomic fragment from an uncultured gamma-proteobacterial sponge symbiont that encodes for four proteins, whose closest known relatives are found in a sponge genome. Through recombinant approaches, we show that these four eukaryotic-like, ankyrin-repeat proteins (ARP) when expressed in Eschericha coli can modulate phagocytosis of amoebal cells and lead to accumulation of bacteria in the phagosome. Mechanistically, two ARPs appear to interfere with phagosome development in a similar way to reduced vacuole acidification, by blocking the fusion of the early phagosome with the lysosome and its digestive enzymes. Our results show that ARP from sponge symbionts can function to interfere with phagocytosis, and we postulate that this might be one mechanism by which symbionts can escape digestion in a sponge host.
Burke, C.M., Liu, M.Y., Britton, W.J., Triccas, J.A., Thomas, T., Smith, A., Allen, S., Salomon, R. & Harry, L. 2013, 'Harnessing Single Cell Sorting To Identify Cell Division Genes And Regulators In Bacteria', Plos One, vol. 8, no. 4, pp. 1-13.
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Cell division is an essential cellular process that requires an array of known and unknown proteins for its spatial and temporal regulation. Here we develop a novel, high-throughput screening method for the identification of bacterial cell division genes and regulators. The method combines the over-expression of a shotgun genomic expression library to perturb the cell division process with high-throughput flow cytometry sorting to screen many thousands of clones. Using this approach, we recovered clones with a filamentous morphology for the model bacterium, Escherichia coli. Genetic analysis revealed that our screen identified both known cell division genes, and genes that have not previously been identified to be involved in cell division. This novel screening strategy is applicable to a wide range of organisms, including pathogenic bacteria, where cell division genes and regulators are attractive drug targets for antibiotic development.
Fan, L., Liu, M., Simister, R., Webster, N.S. & Thomas, T. 2013, 'Marine microbial symbiosis heats up: the phylogenetic and functional response of a sponge holobiont to thermal stress.', The ISME journal, vol. 7, no. 5, pp. 991-1002.
Large-scale mortality of marine invertebrates is a major global concern for ocean ecosystems and many sessile, reef-building animals, such as sponges and corals, are experiencing significant declines through temperature-induced disease and bleaching. The health and survival of marine invertebrates is often dependent on intimate symbiotic associations with complex microbial communities, yet we have a very limited understanding of the detailed biology and ecology of both the host and the symbiont community in response to environmental stressors, such as elevated seawater temperatures. Here, we use the ecologically important sponge Rhopaloeides odorabile as a model to explore the changes in symbiosis during the development of temperature-induced necrosis. Expression profiling of the sponge host was examined in conjunction with the phylogenetic and functional structure and the expression profile of the symbiont community. Elevated temperature causes an immediate stress response in both the host and symbiont community, including reduced expression of functions that mediate their partnership. Disruption to nutritional interdependence and molecular interactions during early heat stress further destabilizes the holobiont, ultimately leading to the loss of archetypal sponge symbionts and the introduction of new microorganisms that have functional and expression profiles consistent with a scavenging lifestyle, a lack virulence functions and a high growth rate. Previous models have postulated various mechanisms of mortality and disease in marine invertebrates. Our study suggests that interruption of symbiotic interactions is a major determinant for mortality in marine sessile invertebrates. High symbiont specialization and low functional redundancy, thus make these holobionts extremely vulnerable to environmental perturbations, including climate change.
Fan, L., Reynolds, D., Liu, M., Stark, M., Kjelleberg, S., Webster, N.S. & Thomas, T. 2012, 'Functional equivalence and evolutionary convergence in complex communities of microbial sponge symbionts.', Proceedings of the National Academy of Sciences of the United States of America, vol. 109, no. 27, pp. E1878-E1887.
Microorganisms often form symbiotic relationships with eukaryotes, and the complexity of these relationships can range from those with one single dominant symbiont to associations with hundreds of symbiont species. Microbial symbionts occupying equivalent niches in different eukaryotic hosts may share functional aspects, and convergent genome evolution has been reported for simple symbiont systems in insects. However, for complex symbiont communities, it is largely unknown how prevalent functional equivalence is and whether equivalent functions are conducted by evolutionarily convergent mechanisms. Sponges represent an evolutionarily divergent group of species with common physiological and ecological traits. They also host complex communities of microbial symbionts and thus are the ideal model to test whether functional equivalence and evolutionary convergence exist in complex symbiont communities across phylogenetically divergent hosts. Here we use a sampling design to determine the phylogenetic and functional profiles of microbial communities associated with six sponge species. We identify common functions in the six microbiomes, demonstrating the existence of functional equivalence. These core functions are consistent with our current understanding of the biological and ecological roles of sponge-associated microorganisms and also provide insight into symbiont functions. Importantly, core functions also are provided in each sponge species by analogous enzymes and biosynthetic pathways. Moreover, the abundance of elements involved in horizontal gene transfer suggests their key roles in the genomic evolution of symbionts. Our data thus demonstrate evolutionary convergence in complex symbiont communities and reveal the details and mechanisms that underpin the process.
Liu, M., Fan, L., Zhong, L., Kjelleberg, S. & Thomas, T. 2012, 'Metaproteogenomic analysis of a community of sponge symbionts.', The ISME journal, vol. 6, no. 8, pp. 1515-1525.
Sponges harbour complex communities of diverse microorganisms, which have been postulated to form intimate symbiotic relationships with their host. Here we unravel some of these interactions by characterising the functional features of the microbial community of the sponge Cymbastela concentrica through a combined metagenomic and metaproteomic approach. We discover the expression of specific transport functions for typical sponge metabolites (for example, halogenated aromatics, dipeptides), which indicates metabolic interactions between the community and the host. We also uncover the simultaneous performance of aerobic nitrification and anaerobic denitrification, which would aid to remove ammonium secreted by the sponge. Our analysis also highlights the requirement for the microbial community to respond to variable environmental conditions and hence express an array of stress protection proteins. Molecular interactions between symbionts and their host might also be mediated by a set of expressed eukaryotic-like proteins and cell-cell mediators. Finally, some sponge-associated bacteria (for example, a Phyllobacteriaceae phylotype) appear to undergo an evolutionary adaptation process to the sponge environment as evidenced by active mobile genetic elements. Our data clearly show that a combined metaproteogenomic approach can provide novel information on the activities, physiology and interactions of sponge-associated microbial communities.
Liu, M.Y., Kjelleberg, S. & Thomas, T. 2011, 'Functional genomic analysis of an uncultured -proteobacterium in the sponge Cymbastela concentrica.', The ISME journal, vol. 5, no. 3, pp. 427-435.
Marine sponges are ancient, sessile, filter-feeding metazoans, which represent a significant component of the benthic communities throughout the world. Sponges harbor a remarkable diversity of bacteria, however, little is known about the functional properties of such bacterial symbionts. In this study, we present the genomic and functional characterization of an uncultured -proteobacterium associated with the sponge Cymbastela concentrica. We show that this organism represents a novel phylogenetic clade and propose that it lives in association with a cyanobacterium. We also provide an overview of the predicted functional and ecological properties of this -proteobacterium, and discuss its complex interactions with surrounding cells and milieu, including traits of cell attachment, nutrient transport and protein-protein interactions.
Cowley, M.J., Cotsapas, C.J., Williams, R.B., Chan, E.K., Pulvers, J.N., Liu, M.Y., Luo, O.J., Nott, D.J. & Little, P.F. 2009, 'Intra- and inter-individual genetic differences in gene expression.', Mammalian genome : official journal of the International Mammalian Genome Society, vol. 20, no. 5, pp. 281-295.
Genetic variation is known to influence the amount of mRNA produced by a gene. Because molecular machines control mRNA levels of multiple genes, we expect genetic variation in components of these machines would influence multiple genes in a similar fashion. We show that this assumption is correct by using correlation of mRNA levels measured from multiple tissues in mouse strain panels to detect shared genetic influences. These correlating groups of genes (CGGs) have collective properties that on average account for 52-79% of the variability of their constituent genes and can contain genes that encode functionally related proteins. We show that the genetic influences are essentially tissue-specific and, consequently, the same genetic variations in one animal may upregulate a CGG in one tissue but downregulate the CGG in a second tissue. We further show similarly paradoxical behaviour of CGGs within the same tissues of different individuals. Thus, this class of genetic variation can result in complex inter- and intraindividual differences. This will create substantial challenges in humans, where multiple tissues are not readily available.