Clinical pathology



The Centre for Systems Genomics is holding a 1-day symposium on metagenomics and microbiome research, Tuesday November 17 at Bio21. 

Interested in presenting? Register now! and complete the abstract section.

This free event will feature talks on a range of microbiome-related topics including new computational and lab methods, covering a range of application areas including the human microbiome in health and disease, environmental metagenomics, ecology, agriculture and ancient DNA.

Event Date: 
Wednesday, June 25, 2014 - 18:00 - 18:15
Institution: 
UNSW
Title: 

Nitric oxide treatment for the control of reverse osmosis membrane biofouling

Abstract: 

Biofouling remains a key challenge for membrane based water treatment systems.  This study investigated the dispersal potential of the nitric oxide (NO) donor compound, PROLI NONOate, on single species biofilms formed by bacteria isolated from industrial membrane bioreactor and reverse osmosis (RO) membranes, as well as on mixed species biofilms.  The potential of PROLI NONOate to control RO membrane biofouling was also examined.  Confocal microscopy revealed that different bacteria responded differently to PROLI NONOate exposure.  However, the addition of NO induced dispersal in all but two of the bacteria tested and successfully reduced mixed species biofilms.  The addition of 40 µM PROLI NONOate at 24 h intervals to a laboratory-scale RO system led to a 92% reduction in the rate of biofouling (pressure rise over a given period) by a bacterial community cultured from an industrial RO membrane.  Confocal microscopy and EPS extraction revealed that PROLI NONOate treatment led to a 48% reduction in polysaccharides, a 66% reduction in proteins and a 29% reduction in microbial cells compared to the untreated control.  A reduction in biofilm surface coverage (59% vs. 98%, treated vs. control) and average thickness (20 µm vs. 26 µm, treated vs. control) was also observed.  The addition of PROLI NONOate led to a 22% increase in the time required for the RO module to reach its maximum TMP, further indicating that NO treatment delayed fouling.  Pyrosequencing analysis revealed that the NO treatment did not significantly alter the microbial community composition of the membrane biofilm.  These results present strong evidence for the application of PROLI NONOate for prevention of RO biofouling in an industrial setting.

Event Date: 
Wednesday, March 26, 2014 - 18:15 - 18:30
Institution: 
Radboud University Nijmegen, Netherlands
Title: 

The gut microbiome of phytopathogenic root fly larvae: insights into the detoxification of plant secondary metabolites by insect-associated microbes

Abstract: 

Plants of the genus Brassica produce various toxic compounds such as isothiocyanates in response to herbivore damage. Despite their toxicity, some insects can cope well with these compounds. One example is the larva of the cabbage root fly (Delia radicum) which is a serious agricultural pest. The mechanism by which these root feeding insects detoxify isothiocyanates is not explored. Our hypothesis is that microorganisms residing in the gut contain enzymes that break down the isothiocyanates and are thus crucial for survival of the root fly larvae. We substantiated this hypothesis by metagenome studies of the microbial gut community. Combined with functional screens of isolated gut microbes these analyses indicated that indeed the gut microbiota plays a vital role in the breakdown of isothiocyanates. Some genes encoding proteins that are involved in this process have already been identified. Ongoing genome and transcriptome studies of isolated gut microbes will enable us to find new candidate genes encoding proteins used for isothiocyanate breakdown that will subsequently be functionally characterized. This will lead to an in-depth understanding of the role of microbes in the plant secondary metabolite – insect interaction.

Event Date: 
Wednesday, February 26, 2014 - 15:45 - 16:15
Institution: 
University of Perugia, Italy
Title: 

The intricate cross-talk of the microbiome in Resistance and Tolerance to pathogens

Abstract: 

The diverse microbial population characterizing the human host represents the result of different complex scenarios impacting the human microbiome assembly. The variety of the microbial species involved plays an important role on the human health by affecting the tissue differentiation, the modulation of the immune system as well as the general response against infectious pathogens, which has been recently revised and divided into two different strategies named Resistance and Tolerance. Resistance being the strategy where the host protects himself by reducing the pathogen load whereby the Tolerance being the opposite strategy, which consists in tolerating the pathogen to avoid tissue damage due to the occurrence of subsequent inflammatory pathologies. The host microbiome seems to play a crucial role in determining which strategy the host will exploit to avoid infection. We recently found that highly adaptive lactobacilli, switching from sugar to Tryptophan (Trp) as an energy source  are expanded and produce an aryl hydrocarbon receptor (AhR) ligand—indole-3-aldehyde—that contributes to AhR-dependent IL-22 transcription, which then trigger the release of antimicrobial peptides by the gut epithelium. Importantly, innate lymphocytes IL-22 producers were already described as a typical innate Resistance strategy to protect the host from intragastrical Candida albicans infections in mice. Thus, the resulting IL-22-dependent balanced mucosal response allows for survival of mixed microbial communities yet provides colonization resistance to the fungus Candida albicans. Therefore, the microbiota-AhR axis might represent an important strategy pursued by co-evolutive commensalism for fine-tuning host mucosal reactivity contingent on Trp catabolism.

Another great JAMS evening at the Australian Museum. Nicolas Barraud from UNSW kicked off with a biotechnology story about the use of nitric oxide in biofilm control. John-Sebastien Eden from Eddie Holmes group at USyd gave us the low down on norovirus evolution using the Sydney 2012 strain (the chunder from downunder) as a case study. Somehow our two 15 min presentations consumed an hour so starting back late after the break JAMS co-founder Prof Andrew Holmes gave an excellent presentation on what shapes microbial communities in the the gut. Despite the late start Andy had the audience glued to their seats with a showcase of technology used to unravel human-gut microbiome interactions.

Event Date: 
Wednesday, October 30, 2013 - 18:00 - 18:15
Institution: 
UNSW
Title: 

NO signals for dispersing biofilms in clinical and industrial applications

Abstract: 

A story from science bench to bedside, or at least towards it What started as purely academic studies of the life cycle of bacterial biofilms, addressing the regulation of cell death events during late developmental stages, led to the discovery of a role for nitric oxide (NO) as a key regulator of biofilm dispersal. NO, which is a simple gas and universal biological signal, was found to be produced endogenously in mature biofilms, and trigger a signaling pathway involving the secondary messenger cyclic di-GMP, which in turn activates cellular effectors resulting in dispersal. Add-back of low levels (picomolar to nanomolar range) of NO was able to induce dispersal across various single species and mixed species biofilms. While the biofilm mode of growth confers a high level of resistance to control measures including antibiotics, exposure to NO greatly increases the efficacy of a range of antimicrobial treatments. Therefore the use of low, non-toxic concentrations of NO represents a promising strategy for the management of biofilms in medical and industrial contexts. Several NO-based technologies have been developed to control bacterial biofilms, including: (i) NO-generating compounds with short or long half-lives and safe or inert residues, (ii) novel materials and surface coatings which catalytically produce NO in situ, and (iii) novel compounds for the targeted delivery of NO to infectious biofilms during systemic treatments.

Event Date: 
Wednesday, October 30, 2013 - 19:00 - 20:00
Institution: 
USyd
Title: 

How microbial community structure is shaped

Abstract: 

 
Microbes profoundly influence biological systems. Owing to their small individual size, but extremely large populations, their influence is typically an emergent property of the microbial community.  As such understanding how microbial community structure is shaped is a generic question relevant to almost all biological systems.
A major focus of my research is the interplay between diet, gut microbiota and health. Our health is the product of interplay between many different factors with arguably three of the most important being adequate nutrition, homeostatic regulation and exclusion of foreign cells. Gut functions influence all these, but occur in the immediate proximity of a huge community of microorganisms – our gut microbiome. The gut microbiome profoundly effects our health via its contribution to and influence on gut functions.
Arguably the most significant aspect of our gut microbiome is that differences in composition matter. The contribution of our microbiome to nutrition, metabolism, gut and immune functions varies from person-to-person. Thus the clinical manifestation of many diseases will be influenced by the individual’s microbiome. Secondly, environmental or lifestyle differences such as diet and hygiene may modulate microbiome composition and thus its influence on health. This gives rise to two basic opportunities for improving healthcare. These are, using the microbiome as a metric to improve diagnosis and targeting the microbiome for therapeutic intervention. We are specifically exploring forces that shape microbial community structure in mouse and human models of with a view to developing diagnostic and intervention strategies across a range of health issues. 

Event Date: 
Wednesday, April 24, 2013 - 19:15 - 20:00
Institution: 
University of Technology Sydney
Title: 

Observing the developing infant gut microbiome with time-series metagenomics.

Abstract: 

The human body plays host to a complex microbial ecosystem, the
development of which begins around the time of birth. Routine monitoring
of the development of microbial ecosystems in newborns (or other
environments) using metagenomic methods is currently extremely
challenging and expensive. I will describe some recent technological
advances that could enable routine sequencing and computational analysis
of hundreds of metagenomes, and demonstrate their application on samples
taken from a developing infant gut microbiome. In this study forty-five
samples were subjected to transposon-catalyzed Illumina library prep and
metagenomic sequencing on a HiSeq 2000 instrument. The resulting data
was subjected to analysis of microbial community structure using a new
approach called phylogenetic Edge Principal Component Analysis (Edge
PCA) that can identify which lineages in a phylogeny explain the
greatest degree of variation among the samples. We also investigate the
population genomics of Bacteroides thetaiotaomicron, one of the dominant
members of the gut microbial community.

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