The young scientists training at the OISB are dedicated, hardworking, innovative and their research is making breakthrough discoveries. We know that. They know that. But the best way to show the world their research discoveries is through peer-reviewed publications. To celebrate their accomplishments, the OISB has created publications of the year award for trainees at the level of MSc, PhD and postdoctoral fellows (PDF). With over 100 publications a year from OISB member labs, picking the winners was no small task; indeed we had a tie for the best PDF paper.
The OISB is pleased to announce the winners of our 2014 Trainee Publications were Shivapriya Chithambaram (MSc), Sylvain Lanoutte (PhD) and Dr Michael Kennedy and Dr Cheng-Kang (Kerwin) Chiang (PDF).
Shivapriya Chithambaram’s MSc work, which was published in Genetics focuses on understanding how bacteria evolve to optimize building proteins and how they can harness this knowledge to re-engineer microbes for use in medical and industrial purposes.
Sylvain Lanouette’s Structure paper presents a novel method to find downstream targets of enzyme called SMYD2 that is misregulated in Oeophageal carcinomas, potentially identify novel avenues of therapeutic intervention.
Dr. Kerwin Chiang’s large-scale proteomic study published in PLoS Genetics determined that a surprisingly large number of pathways and cellular processes in mice are up and down regulated by circadian rhymes or sleep/activity patterns.
Dr. Michael Kennedy’s research published in PLoS Genetics utilizes numerous systems biology, or high throughput, approaches and model systems, to determine how the lipids that are dysregulated during Alzheimer’s disease impact the progression of the disease.
Below are more details and lay summaries of the papers submitted by the nominees and/or supervisors.
Dr. Michael Kennedy
Supervisors: Kristin Baetz and Steffany Bennett, Department of Biochemistry, Microbiology and Immunology.
A Neurotoxic Glycerophosphocholine Impacts PtdIns-4, 5-Bisphosphate and TORC2 Signaling by Altering Ceramide Biosynthesis in Yeast. PLoS Genetics (2014)10-e1004010
Alzheimer’s disease (AD) impacts over 15% of Canadians over the age of 65 with an estimated economic impact $33 billion per year. Mysregulation of lipid regulation is a hallmark of and contributor to AD progression by largely unknown mechanisms. Importantly this study provides important mechanistic and biochemical insight about how a lipid known to contribute to AD pathology triggers the activation of a signaling pathway contributing to cell death. Therapeutic strategies which target this signaling pathway may be effective against AD pathology; hence this work has identified potential novel therapeutic strategies to treat the growing challenges of AD in Canada.
Dr. Cheng-Kang (Kerwin) Chiang
Supervisor: Dan Figeys, Department of Biochemistry, Microbiology and Immunology
The Proteomic Landscape of the Suprachiasmatic Nucleus Clock Reveals Large-Scale Coordination of Key Biological Processes. PLoS Genetics (2014) 10(10):e1004695
1. In this paper, our unbiased interrogation of the SCN proteome shows 3409 unique proteins in the SCN—the largest coverage of the SCN proteome that has been reported to date—, of which 441 exhibited time-of-day-dependent variations and could be binned into a small number (i.e. 6) hierarchical clusters based on expression pattern.
2. The vast majority of these temporally regulated expressed proteins did not overlap with the “circadianly expressed” transcripts that were identified in previous gene profiling microarray studies (Panda et al., 2002), and a large proportion of the rhythmic proteome exhibited rhythms that were not circadian per se, but were ultradian with periodicities of 8 or 12 h.
3. Given the poor correlation between the circadian transcriptome and proteome, our bioinformatic analysis also revealed that the in silico targets of miR-133ab were highly enriched in specific hierarchical clusters, suggesting that miRNA may help to define the temporal kinetics of a large group of proteins within a particular cluster.
4. Our proteomics data revealed the widespread control that the SCN clock has over the mitochondrial oxidative phosphorylation (OxPhox) pathway; in fact, all of the protein complexes involved in the electron transport chain (complexes I through V) are regulated by the clock, with complexes I and V being most heavily regulated.
Supervisor: Jean-Francois Couture, Department of Biochemistry, Microbiology and Immunology.
Discovery of Substrates for a SET Domain Lysine Methyltransferase Predicted by Multistate Computational Protein Design. Structure. 2015 Jan 6;23(1):206-15. doi: 10.1016/j.str.2014.11.004. Epub 2014 Dec 18.
Oeophageal carcinomas (OC) is an aggressive cancer with a 5-year survival rate of 15%. In OC, the activity of the oncogene lysine methyltransferase SMYD2 is uncontrolled which results in the aberrant methylation of several proteins; yet the extent of the proteins modified by this enzyme is unknown. In his paper entitled "Discovery of Substrates for a SET Domain Lysine Methyltransferase Predicted by Multistate Computational Protein Design" Sylvain presents a novel, rapid and inexpensive approach to determine all SMYD2 substrates. This paper open new avenues for therapeutic interventions for treating OC and pave the way to the characterization of other cancer-related protein modifying enzymes.
Supervisor: Xuhua Xia, Department of Biology
The Effect of Mutation and Selection on Codon Adaptation in Escherichia coli Bacteriophage. Genetics, Vol. 197, 301–315 May 2014
Studying phage codon adaptation is important not only for understanding the process of translation elongation, but also for re-engineering phages for medical and industrial purposes. We developed a new codon usage index as well as linear and nonlinear models to quantify the effect of mutation and selection (mediated by host tRNA pool) on phage codon usage. C®T biased mutations, host tRNA-mediated selection, and strand asymmetry all contribute significantly to codon usage in ssDNA and dsDNA phages, but their effects differ significantly between the two type of phages.