To improve the power of Learning Portfolios to enable long-term peer-to-peer mentoring between McMaster students and alumni, this Learning Portfolio Fellowship will establish a centralized database which can be used by students to formulate effective learning and career action plans based on current and past student experiences. The research question for this Learning Portfolio Fellowship is: “Can a meta-analysis based Learning Portfolio database contribute towards the undergraduate student career action plan?” While Learning Portfolios are effective qualitative measures of student outcomes, the proposed research will analyze current portfolios and capture quantitative metrics pertaining to the courses, experiential placements, volunteer opportunities, and extracurricular opportunities obtained by students pursuing various programs and career paths. Once the meta-analysis is conducted, the database will allow students to enter search queries, which will link them to collected repositories of information on their prospective career path.
This project is a collaboration with Dr. Rosa da Silva of McMaster’s Biology Department (pictured).
McMaster Innovation Showcase 2014 is an opportunity for the University to demonstrate the exciting technologies that have been developed at McMaster, feature the initiatives underway relating to entrepreneurship, and engage with the community.
When: November 12, 2014; 8:00am – 5:00pm Where: McMaster Innovation Park Atrium, First Floor
More information on Keynote address, roundtable discussion, and Open Doors can be found here.
Smith, E.M., A.G. McArthur, M. Galus, S. Higgins, N. Kirischian, J. Jeyaranjaan, & J.Y. Wilson. 2014. Transcriptional responses of zebrafish to pharmaceutical and wastewater exposure: are single compound exposures predictive of mixtures? Keynote presentation at the Aquatic Toxicology Workshop 2014, Ottawa, Canada.
Human pharmaceuticals have been well documented in receiving waters yet their impacts on aquatic species are not clear. We have exposed adult zebrafish for 6 weeks to waterborne acetaminophen, gemfibrozil, venlafaxine, and carbamazepine at two doses (0.5 and 10 μg L-1). Fish were then exposed to a mixture of all four pharmaceuticals or wastewater effluent (5 and 25%) to assess whether transcriptional responses are similar with mixtures.. For all exposures, reproduction was significantly reduced and histopathological changes induced in kidney with at least the high dose exposure. Livers were pooled to provide sufficient RNA for microarray analyses. Hepatic transcriptional responses were determined with a modified Agilent 44K zebrafish microarry using a single channel approach. Significantly different probes were identified with a 2-way ANOVA (sex and treatment) and rank product analyses with a 10% false discovery rate. Transcriptional responses were particularly marked with acetaminophen exposure and there was broad overlap in the significant probes found between doses and across gender for this compound. 52 probes were at least 20 fold up- or down- regulated in acetaminophen exposed fish; 3 probes were 100 fold up-regulated (apolipoprotein Eb precursor, cdc73, and a hypothetical protein). Unique probes were identified for all exposures suggesting a unique transcriptional response may occur for each pharmaceutical, the pharmaceutical mixture, and wastewater effluent. Interestingly, there was almost no overlap in the transcriptional response found with single pharmaceutical exposure and either the mixture or wastewater effluent exposure. Indeed, the large transcriptional response from acetaminophen exposure was largely absent in fish exposed to the pharmaceutical mixture and wastewater effluent. This suggests that identifying individual or clusters of genes that may be useful in effects based monitoring may be difficult for pharmaceutical compounds.
Andrew McArthur will be returning to academia in September 2014 to join McMaster University as the Cisco Chair in Bioinformatics and Associate Professor in the Department of Biochemistry & Biomedical Sciences in the Faculty of Health Sciences. Read more about the McMaster – Cisco collaboration at: McMaster and Cisco collaborate to further bioinformatics research and build institutional research cloud.
The metal responsive element-binding transcription factor-1 (MTF-1) responds to changes in cellular zinc levels caused by zinc exposure or disruption of endogenous zinc homeostasis by heavy metals or oxygen-related stress. Here we report the functional characterization of a complete zebrafish MTF-1 in comparison with the previously identified isoform lacking the highly conserved cysteine-rich motif (Cys-X-Cys-Cys-X-Cys) found in all other vertebrate MTF-1 orthologs. In an effort to develop novel molecular tools, a constitutively nuclear dominant-negative MTF-1 (dnMTF-1) was generated as tool for inhibiting endogenous MTF-1 signaling. The in vivo efficacy of the dnMTF-1 was determined by microinjecting in vitro transcribed dnMTF-1 mRNA into zebrafish embryos (1-2 cell stage) followed by transcriptomic profiling using an Agilent 4x44K array on 28- and 36-hpf embryos. A total of 594 and 560 probes were identified as differentially expressed at 28 hpf and 36 hpf, respectively, with interesting overlaps between timepoints. The main categories of genes affected by the inhibition of MTF-1 signaling were: nuclear receptors and genes involved in stress signaling, neurogenesis, muscle development and contraction, eye development, and metal homeostasis, including novel observations in iron and heme homeostasis. Finally, we investigate both the transcriptional activator and transcriptional repressor role of MTF-1 in potential novel target genes identified by transcriptomic profiling during early zebrafish development.
Williams, L.E., A.G. McArthur, N. Waglechner, F. Nizam, P.T. Desai, M. McClelland, G.M. Weinstock, J.B. Barrett, L.M. Hiott, C.R. Jackson, & J.G. Frye. 2014. Genetic variation and genomic context of antibiotic resistance genes and mobile genetic elements in Salmonella from non-human animals. Presentation at the 114th General Meeting of the American Society for Microbiology, Boston, Massachusetts.
Zittermann, S.I., A.G. McArthur, N.V. Fittipaldi, V. Braun, L. Vrbova, D. Middleton, G. Mallo, R. Ahmed, P. Huk, M. Lombos, V.G. Allen. 2014. Whole genome sequencing of Salmonella Enteritidis for public health investigation. Presentation at the 114th General Meeting of the American Society for Microbiology, Boston, Massachusetts.
Transcription factors in the CNC-bZIP family (NFE2, NRF1, NRF2 and NRF3) regulate genes with a wide range of functions in response to both physiological and exogenous signals, including those indicating changes in cellular redox status. Given their role in helping to maintain cellular homeostasis, it is imperative to understand the expression, regulation, and function of CNC-bZIP genes during embryonic development. We explored the expression and function of six nrf genes (nfe2, nrf1a, nrf1b, nrf2a, nrf2b, and nrf3) using zebrafish embryos as a model system. Analysis by microarray and quantitative RT-PCR showed that genes in the nrf family were expressed throughout development from oocytes to larvae. The spatial expression of nrf3 suggested a role in regulating the development of the brain, brachia and pectoral fins. Knock-down by morpholino anti-sense oligonucleotides suggested that none of the genes were necessary for embryonic viability, but nfe2 was required for proper cellular organization in the pneumatic duct and subsequent swim bladder function, as well as for proper formation of the otic vesicles. nrf genes were induced by the oxidant tert-butylhydroperoxide, and some of this response was regulated through family members Nrf2a and Nrf2b. Our results provide a foundation for understanding the role of nrf genes in normal development and in regulating the response to oxidative stress in vertebrate embryos.
Authors: AG McArthur, N Waglechner, F Nizam, A Yan, MA Azad, AJ Baylay, K Bhullar, MJ Canova, G De Pascale, L Ejim, L Kalan, AM King, K Koteva, M Morar, MR Mulvey, JS O’Brien, AC Pawlowski, LJV Piddock, P Spanogiannopoulos, AD Sutherland, I Tang, PL Taylor, M Thaker, W Wang, M Yan, T Yu, & GD Wright
The field of antibiotic drug discovery and the monitoring of new antibiotic resistance elements have yet to fully exploit the power of the genome revolution. Despite the fact that the first genomes sequenced of free living organisms were those of bacteria, there have been few specialized bioinformatic tools developed to mine the growing amount of genomic data associated with pathogens. In particular, there are few tools to study the genetics and genomics of antibiotic resistance and how it impacts bacterial populations, ecology, and the clinic. We have initiated development of such tools in the form of the Comprehensive Antibiotic Research Database (CARD; http://arpcard.mcmaster.ca). The CARD integrates disparate molecular and sequence data, provides a unique organizing principle in the form of the Antibiotic Resistance Ontology (ARO), and can quickly identify putative antibiotic resistance genes in new unannotated genome sequences. This unique platform provides an informatic tool that bridges antibiotic resistance concerns in health care, agriculture, and the environment.
Karchner, S.I., D.G. Franks, A.R. Timme-Laragy, A.G. McArthur, & M.E. Hahn. 2013. Chemical-specific oxidative stress response in zebrafish embryos. Presentation at the Pollutant Responses in Marine Organisms (PRIMO 17) Meeting, Faro, Portugal. Exposure to natural and anthropogenic stressors often leads to oxidative stress—a disruption in the regulation of intracellular redox conditions. Animals have evolved protective responses to mitigate damage caused by oxidative stress. However, the mechanisms by which the oxidative stress response is regulated during development are poorly understood. Oxidants, electrophiles, and some phenolic anti-oxidants initiate this response by activating NF-E2-related factor 2 (NRF2) and related cap’n’collar (CNC)- basic-leucine zipper (bZIP) family proteins, which bind to the anti-oxidant response element (ARE) and activate transcription of genes such as glutathione S-transferases (GST), NAD(P)H-quinone oxidoreductase (NQO1), glutamate-cysteine ligase (GCL), and superoxide dismutase (SOD). In order to determine the genes that are induced or repressed in response to oxidative stress during development, and whether there is a “core” set of oxidant responsive genes that is induced by structurally distinct activators of NRF2, zebrafish (Danio rerio) larvae (96 hours post-fertilization) were exposed to model oxidants (tert-butylhydroquinone (tBHQ), tert-butylhydroperoxide (tBOOH), diquat (DQ) or sulforaphane (SFN)) and gene expression was measured 6 hr later by microarray and Q-RT-PCR. There was a robust response to oxidative stress by all chemicals, with a total of 1281 probes significantly altered in expression. The compounds caused overlapping but distinct patterns of altered gene expression. A core set of genes responded to all oxidants. However, other genes exhibited oxidant-specific changes in expression. Principal components analysis revealed that the changes in gene expression caused by SFN, a sulfhydryl-reactive agent, were distinct from those produced by the other oxidants. The results demonstrate that the oxidative stress response in developing animals is dependent upon the nature of the oxidative stress.