Publications by authors named "Michelle Coombe"

10 Publications

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A SYSTEMATIC REVIEW AND NARRATIVE SYNTHESIS OF THE USE OF ENVIRONMENTAL SAMPLES FOR THE SURVEILLANCE OF AVIAN INFLUENZA VIRUSES IN WILD WATERBIRDS.

J Wildl Dis 2021 Jan;57(1):1-18

University of British Columbia, School of Population and Public Health, 2206 E Mall, Vancouver, British Columbia V6T 1Z3, Canada.

Wild waterbirds are reservoir hosts for avian influenza viruses (AIV), which can cause devastating outbreaks in multiple species, making them a focus for surveillance efforts. Traditional AIV surveillance involves direct sampling of live or dead birds, but environmental substrates present an alternative sample for surveillance. Environmental sampling analyzes AIV excreted by waterbirds into the environment and complements direct bird sampling by minimizing financial, logistic, permitting, and spatial-temporal constraints associated with traditional surveillance. Our objectives were to synthesize the literature on environmental AIV surveillance, to compare and contrast the different sample types, and to identify key themes and recommendations to aid in the implementation of AIV surveillance using environmental samples. The four main environmental substrates for AIV surveillance are feces, feathers, water, and sediment or soil. Feces were the most common environmental substrate collected. The laboratory analysis of water and sediment provided challenges, such as low AIV concentration, heterogenous AIV distribution, or presence of PCR inhibitors. There are a number of abiotic and biotic environmental factors, including temperature, pH, salinity, or presence of filter feeders, that can influence the presence and persistence of AIV in environmental substrates; however, the nature of this influence is poorly understood in field settings, and field data from southern, coastal, and tropical ecosystems are underrepresented. Similarly, there are few studies comparing the performance of environmental samples to each other and to samples collected in wild waterbirds, and environmental surveillance workflows have yet to be validated or optimized. Environmental samples, particularly when used in combination with new technology such as environmental DNA and next generation sequencing, provided information on trends in AIV detection rates and circulating subtypes that complemented traditional, direct waterbird sampling. The use of environmental samples for AIV surveillance also shows significant promise for programs whose goal is early warning of high-risk subtypes.
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http://dx.doi.org/10.7589/JWD-D-20-00082DOI Listing
January 2021

Scoping Review and Bibliometric Analysis of the Term "Planetary Health" in the Peer-Reviewed Literature.

Front Public Health 2020 29;8:343. Epub 2020 Jul 29.

The George Institute for Global Health, University of Oxford, Oxford, United Kingdom.

Planetary health is an emerging holistic health field to foster interdisciplinary collaborations, integrate Indigenous knowledge, facilitate education, and drive public and policy engagement. To understand to what extent the field has successfully met these goals, we conducted a scoping review and bibliometric analysis. We searched 15 databases from 2005 to 2019 for peer-reviewed publications with the term "planetary health" in the title, abstract and/or keywords, with no language or geographical location limitations. We classified results into four categories (commentaries, comprehensive syntheses, educational material, and original research) and categorized original research according to expert-derived planetary health themes. Our bibliometric analysis highlighted publications over time, collaborations, and networks of keywords. Only 8.1% ( = 22) were research articles. Publications rose rapidly from 8 to 64 publications per year in 2015-2018. The top five author affiliation countries for most publications were the US, UK, Australia, Canada, and New Zealand, and the top five collaborations were a subset of pairwise combinations between the US, UK, Australia, and Canada. The most common author keywords were the following: planetary health, climate change, ecology, and non-communicable diseases. Keyword co-occurrences clustered around high-level concepts (e.g., Anthropocene) and food system-related topics; two clusters lacked a theme. We show that the term planetary health is used mainly in commentary-like publications, not original research. Additionally, more global collaborations are lacking. Interdisciplinary work, as represented by keyword co-occurrence networks, is developing but could potentially be extended. The planetary health community should promote more worldwide research and interdisciplinary collaborations.
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http://dx.doi.org/10.3389/fpubh.2020.00343DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7403469PMC
July 2020

Evidence for transmission of COVID-19 prior to symptom onset.

Elife 2020 06 22;9. Epub 2020 Jun 22.

Simon Fraser University, Burnaby, Canada.

We collated contact tracing data from COVID-19 clusters in Singapore and Tianjin, China and estimated the extent of pre-symptomatic transmission by estimating incubation periods and serial intervals. The mean incubation periods accounting for intermediate cases were 4.91 days (95%CI 4.35, 5.69) and 7.54 (95%CI 6.76, 8.56) days for Singapore and Tianjin, respectively. The mean serial interval was 4.17 (95%CI 2.44, 5.89) and 4.31 (95%CI 2.91, 5.72) days (Singapore, Tianjin). The serial intervals are shorter than incubation periods, suggesting that pre-symptomatic transmission may occur in a large proportion of transmission events (0.4-0.5 in Singapore and 0.6-0.8 in Tianjin, in our analysis with intermediate cases, and more without intermediates). Given the evidence for pre-symptomatic transmission, it is vital that even individuals who appear healthy abide by public health measures to control COVID-19.
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http://dx.doi.org/10.7554/eLife.57149DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7386904PMC
June 2020

Extraction and Detection of Avian Influenza Virus From Wetland Sediment Using Enrichment-Based Targeted Resequencing.

Front Vet Sci 2020 29;7:301. Epub 2020 May 29.

Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.

Early virus detection and characterization is key to successful avian influenza virus (AIV) surveillance for the health of humans as well as domestic poultry. We explored a novel sampling approach and molecular strategy using sediment from wetlands and outdoor waterbodies on poultry farms as a population-level proxy of AIV activity in waterfowls. RNA was extracted using the MoBio RNA PowerSoil Total RNA isolation kit with additional chloroform extraction steps to reduce PCR inhibition. AIV matrix protein (MP) gene was detected in 42/345 (12.2%) samples by RT-qPCR; an additional 64 (18.6%) samples showed evidence of amplification below the threshold and were categorized as "suspect positive." Enrichment-based targeted resequencing (TR) identified AIV sequences in 79/345 (22.9%) samples. TR probes were designed for MP, hemagglutinin (HA), and neuraminidase (NA), however PB2 and PA were also identified. Although RT-qPCR and TR only had fair-moderate agreement, RT-qPCR positivity was predictive of TR-positivity both when using only strictly positive RT-qPCR samples (OR = 11.29) and when coding suspect positives as positive (OR = 7.56). This indicates that RT-qPCR could be used as a screening tool to select samples for virus characterization by TR and that future studies should consider RT-qPCR suspect positives to be positive samples for subsequent resequencing when avoiding false negatives is the priority, for instance in a diagnostic test, and to consider suspect positives to be negative samples when cost efficiency over a large number of samples is the priority, for instance in a surveillance program. A total of 13 HA (H1-7, H9-13, H16) and 9 NA (N1-9) subtypes were identified, with a maximum of 8 HA and 8 NA subtypes detected in a single sample. The optimized RNA extraction and targeted resequencing methods provided increased virus detection and subtyping characterization that could be implemented in an AIV surveillance system.
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http://dx.doi.org/10.3389/fvets.2020.00301DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7273442PMC
May 2020

TARGETED RESEQUENCING OF WETLAND SEDIMENT AS A TOOL FOR AVIAN INFLUENZA VIRUS SURVEILLANCE.

J Wildl Dis 2020 04 21;56(2):397-408. Epub 2019 Nov 21.

University of British Columbia, Department of Pathology and Laboratory Medicine, 2211 Wesbrook Mall, Vancouver, British Columbia V6T 2B5, Canada.

Surveillance methods for avian influenza virus (AIV) based upon collecting and testing samples from individual wild birds have several significant limitations primarily related to the difficulties associated with obtaining samples. Because AIVs are shed in waterfowl feces, the use of environmental substrates where waterfowl feces accumulate may overcome some of these limitations. However, these substrates are difficult to analyze using traditional diagnostic techniques, such as virus culture and PCR, because of virus inactivation, RNA degradation, low concentration of target RNA, microbial complexity, presence of inhibitory substances, and other factors. We investigated the use of a genomics-based approach called targeted resequencing to detect and characterize AIVs in wetland sediments during the 2014-15 North American highly pathogenic avian influenza outbreak. We identified AIV in 20.6% (71/345) sediment samples obtained from wetlands (=15) and outdoor waterbodies on AIV-infected poultry farms (=10) in British Columbia, Canada (the first area affected during the outbreak). Thirteen hemagglutinin (HA) and nine neuraminidase (NA) subtypes were detected, including H5, N1, and N8 sequences that clustered with other sequences associated with the North American outbreak. Additionally, as many as eight HA and eight NA subtypes could be detected in a single sediment sample. This proof-of-concept study shows the potential utility of sediment sampling coupled with genomics-based analysis as a tool for AIV surveillance.
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April 2020

A genetic screen for dominant modifiers of a cyclin E hypomorphic mutation identifies novel regulators of S-phase entry in Drosophila.

Genetics 2004 Sep;168(1):227-51

Peter MacCallum Cancer Centre, East Melbourne, Victoria, 3002, Australia.

Cyclin E together with its kinase partner Cdk2 is a critical regulator of entry into S phase. To identify novel genes that regulate the G1- to S-phase transition within a whole animal we made use of a hypomorphic cyclin E mutation, DmcycEJP, which results in a rough eye phenotype. We screened the X and third chromosome deficiencies, tested candidate genes, and carried out a genetic screen of 55,000 EMS or X-ray-mutagenized flies for second or third chromosome mutations that dominantly modified the DmcycEJP rough eye phenotype. We have focused on the DmcycEJP suppressors, S(DmcycEJP), to identify novel negative regulators of S-phase entry. There are 18 suppressor gene groups with more than one allele and several genes that are represented by only a single allele. All S(DmcycEJP) tested suppress the DmcycEJP rough eye phenotype by increasing the number of S phases in the postmorphogenetic furrow S-phase band. By testing candidates we have identified several modifier genes from the mutagenic screen as well as from the deficiency screen. DmcycEJP suppressor genes fall into the classes of: (1) chromatin remodeling or transcription factors; (2) signaling pathways; and (3) cytoskeletal, (4) cell adhesion, and (5) cytoarchitectural tumor suppressors. The cytoarchitectural tumor suppressors include scribble, lethal-2-giant-larvae (lgl), and discs-large (dlg), loss of function of which leads to neoplastic tumors and disruption of apical-basal cell polarity. We further explored the genetic interactions of scribble with S(DmcycEJP) genes and show that hypomorphic scribble mutants exhibit genetic interactions with lgl, scab (alphaPS3-integrin--cell adhesion), phyllopod (signaling), dEB1 (microtubule-binding protein--cytoskeletal), and moira (chromatin remodeling). These interactions of the cytoarchitectural suppressor gene, scribble, with cell adhesion, signaling, cytoskeletal, and chromatin remodeling genes, suggest that these genes may act in a common pathway to negatively regulate cyclin E or S-phase entry.
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http://dx.doi.org/10.1534/genetics.104.026617DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1448096PMC
September 2004

Drosophila Hfp negatively regulates dmyc and stg to inhibit cell proliferation.

Development 2004 Mar;131(6):1411-23

Trescowthick Research Laboratories, Peter MacCallum Cancer Centre, St Andrew's Place, East Melbourne, VIC 3002 Australia.

Mammalian FIR has dual roles in pre-mRNA splicing and in negative transcriptional control of Myc. Here we show that Half pint (Hfp), the Drosophila orthologue of FIR, inhibits cell proliferation in Drosophila. We find that Hfp overexpression potently inhibits G1/S progression, while hfp mutants display ectopic cell cycles. Hfp negatively regulates dmyc expression and function, as reducing the dose of hfp increases levels of dmyc mRNA and rescues defective oogenesis in dmyc hypomorphic flies. The G2-delay in dmyc-overexpressing cells is suppressed by halving the dosage of hfp, indicating that Hfp is also rate-limiting for G2-M progression. Consistent with this, the cycle 14 G2-arrest of stg mutant embryos is rescued by the hfp mutant. Analysis of hfp mutant clones revealed elevated levels of Stg protein, but no change in the level of stg mRNA, suggesting that hfp negatively regulates Stg via a post-transcriptional mechanism. Finally, ectopic activation of the wingless pathway, which is known to negatively regulate dmyc expression in the wing, results in an accumulation of Hfp protein. Our findings indicate that Hfp provides a critical molecular link between the developmental patterning signals induced by the wingless pathway and dMyc-regulated cell growth and proliferation.
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http://dx.doi.org/10.1242/dev.01019DOI Listing
March 2004

hScrib is a functional homologue of the Drosophila tumour suppressor Scribble.

Oncogene 2003 Dec;22(58):9225-30

Cell Cycle and Cancer Genetics Laboratory, Peter MacCallum Cancer Centre, St Andrew's Place, East Melbourne, Victoria 3002, Australia.

Scribble (scrib), discs large (dlg) and lethal giant larvae (lgl) encode proteins that regulate cell polarity and have been identified as neoplastic tumour suppressor genes in Drosophila melanogaster. Here, we have used the Drosophila model system to provide the first functional evidence that human Scribble (hScrib) can act as a tumour suppressor. We show that hScrib protein displays highly polarized localization in mammalian epithelial cells and colocalizes with mammalian Dlg, similar to D. melanogaster Scribble (DmScrib) distribution in Drosophila epithelium. Furthermore, hScrib can rescue the polarity and tumorous overgrowth defects of scrib mutant Drosophila. hScrib therefore can act as an effective tumour suppressor in vivo, regulating both apical-basal polarity and cellular proliferation in a manner similar to that of DmScrib in Drosophila. These data demonstrate that hScrib is a functional homologue of DmScrib and therefore predict an important role for hScrib in the suppression of mammalian tumorigenesis.
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http://dx.doi.org/10.1038/sj.onc.1207154DOI Listing
December 2003

Buffy, a Drosophila Bcl-2 protein, has anti-apoptotic and cell cycle inhibitory functions.

EMBO J 2003 Jul;22(14):3568-79

Trescowick Research Laboratories, Peter MacCallum Cancer Institute, St Andrews Place, East Melbourne.

Bcl-2 family proteins are key regulators of apoptosis. Both pro-apoptotic and anti-apoptotic members of this family are found in mammalian cells, but only the pro-apoptotic protein Debcl has been characterized in Drosophila: Here we report that Buffy, the second Drosophila Bcl-2-like protein, is a pro-survival protein. Ablation of Buffy by RNA interference leads to ectopic apoptosis, whereas overexpression of buffy results in the inhibition of developmental programmed cell death and gamma irradiation-induced apoptosis. Buffy interacts genetically and physically with Debcl to suppress Debcl-induced cell death. Genetic interactions suggest that Buffy acts downstream of Rpr, Grim and Hid, and upstream of the apical caspase Dronc. Furthermore, overexpression of buffy inhibits ectopic cell death in diap1 (th(5)) mutants. Taken together these data suggest that Buffy can act downstream of Rpr, Grim and Hid to block caspase-dependent cell death. Overexpression of Buffy in the embryo results in inhibition of the cell cycle, consistent with a G(1)/early-S phase arrest. Our data suggest that Buffy is functionally similar to the mammalian pro-survival Bcl-2 family of proteins.
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http://dx.doi.org/10.1093/emboj/cdg355DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC165625PMC
July 2003

Analysis of Drosophila cyclin EI and II function during development: identification of an inhibitory zone within the morphogenetic furrow of the eye imaginal disc that blocks the function of cyclin EI but not cyclin EII.

Dev Biol 2002 Jan;241(1):157-71

Center for the Molecular Genetics of Development and Department of Molecular Biosciences, University of Adelaide, Adelaide, South Australia, 5005, Australia.

The Drosophila cyclin E (DmcycE) gene gives rise to two transcripts encoding proteins that differ at their N termini, DmcycEII and DmcycEI. This study presents the first in vivo dissection of Cyclin E function. Ectopic expression studies using N- and C-terminal deletions of DmcycEI revealed that a region of 322 residues surrounding the cyclin box is sufficient to induce entry of G1-arrested larval eye imaginal disc cells into S phase. Ectopic expression of DmcycEI in the eye disc has been previously shown to drive anterior, but not posterior, G1-phase cells within the morphogenetic furrow (MF) into S phase. Significantly, ectopic expression of DmcycEII and N-terminal deletions of DmcycEI were able to drive all G1 cells within the morphogenetic furrow into S phase, while a C-terminal deletion of DmcycEI could not. The p21 homolog Dacapo was shown by yeast two-hybrid, coimmunolocalization, and in vivo functional studies not to be the mediator of the DmcycEI inhibition in posterior part of the MF. Taken together, these results reveal a novel zone within the posterior region of the MF where DmcycEI but not DmcycEII function is inhibited, and suggest that DmcycEII is a more potent inducer of S phase.
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http://dx.doi.org/10.1006/dbio.2001.0496DOI Listing
January 2002