ARRTI Speaker Series - 2017

December 13, 2017

Dr. Richard Fahlman

University of Alberta
Department of Biochemistry
Edmonton, Alberta, Canada

"Non-Canonical Roles for the Translational Machinery in Proteostasis - Insights into Alternative Functions for tRNAs and Ribosomes in Gene Expression"

A central concept in biology regarding gene expression is that the information encoded in our genes is translated into proteins that carry out the functions in a cell. In this process, the molecular machines responsible for the translation also play roles in regulating which genes are translated into proteins in a given cell.  This regulation explains why cells within different tissues and organs are very dissimilar, despite them all having identical genomes. In diseases such as cancer, there is often a dysregulation of which genes are being translated, which can lead to the aggressive growth behavior of tumors. My research into new mechanisms of gene expression is revealing the details on how tumors are so different than their original tissue, and is discerning new ways we may be able to combat these diseases.

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December 6, 2017

Dr. Andrea Gorrell

University of Northern British Columbia
Department of Biochemistry and Molecular Biology
Prince George, British Columbia, Canada

"Haloarcula marismortui Gene Expression Profiling Under Potassium Stress Conditions"

The research in the lab focuses on structure/function studies of enzymatic reactions, with an emphasis on reactions which occur in the archaea.

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September 1, 2017

Dr. Min-Xin Guan

Zhejiang University
School of Medicine, Professor of Genetics and Medicine
Hangzhou, Zhejiang, China

"Mitochondrial tRNA mutations associated with hearing loss"

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August 4, 2017

Dr. Borries Demeler

The University of Texas Health Science Center
Department of Biochemistry
San Antonio, Texas, USA

"Measuring Interactions in the Solution Phase: Adding a Spectral Dimension to Analytical Ultracentrifugation"

Ever since Svedberg's Nobel prize, Analytical Ultracentrifugation (AUC) has been regarded as the gold standard for first-principle solution-based interaction analysis. With the arrival of the latest detector technology, an entirely new class of experiments has become possible. Multi-wavelength detection adds an orthogonal spectral dimension to the hydrodynamic characterization of solutes, allowing components with distinct absorbance spectra to be identified based on their optical properties. In this talk, I will describe novel insights gained from this new technology and discuss examples involving spectral separation of protein-nucleic acid interactions, determination of stoichiometry of West Nile virus RNA interactions with host cell proteins, and the elucidation of quantum gap spectra and reaction mechanisms of CdTe quantum dots.

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June 19, 2017

Dr. Ian Lewis

University of Calgary
Department of Biological Sciences
Calgary, Alberta, Canada

"Predicting disease from metabolites: the challenges and opportunities in state-of-the-art metabolomics"

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June 5, 2017

Dr. Ramon Grima

University of Edinburgh
School of Biological Sciences
Edinburgh, Scotland

"Mean field theory of diffusion in heterogeneous intracellular crowded conditions"

It is now well established that cell interiors are significantly crowded by macromolecules, which impede diffusion and enhance binding rates. However, it is not fully appreciated that levels of crowding are heterogeneous, and can vary substantially between subcellular regions. Starting from a stochastic microscopic model, we derive coupled nonlinear PDEs for the concentrations of two populations of large and small spherical particles with steric volume exclusion. By performing a perturbative expansion in the ratio of the particle sizes, we find that the diffusion of a small particle in the presence of large particles obeys an advection-diffusion equation, with a reduced diffusion coefficient and a velocity directed towards less crowded regions. The interplay between advection and diffusion leads to behaviour that differs significantly from Brownian diffusion. We show that biologically plausible distributions of macromolecules can lead to (i) highly non-Gaussian probability densities for the small particle position, including asymmetrical and multimodal densities, (ii) both sub- and super-diffusion for short times. We confirm all our results using hard-sphere Brownian dynamics simulations.

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May 9, 2017

Dr. Igor Kovalchuk

University of Lethbridge
Department of Biological Sciences
Lethbridge, Alberta, Canada

"Role of non-coding RNAs and non-coding RNA fragments in the regulation of genome stability and gene expression"

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April 21, 2017

Dr. Sean McKenna

University of Manitoba
Department of Chemistry & Department of Biochemistry and Medical Genetics
Winnipeg, Manitoba, Canada

"Investigations into a long non-coding RNA critical for cancer cell survival and proliferation"

BC200 is a 200 nt primate-specific long non-coding RNA expressed at high levels in brain. In addition to brain, BC200 is expressed at moderate levels in testes and is over-expressed in wide variety of tumours and tumour-derived cell lines. BC200 is postulated to play a role in translational regulation of a subset of mRNAs, possibly acting as a key regulator of site specific protein translation. Data concerning the role of BC200 in neural tissue as well as tumour cells is preliminary and to date no mRNAs directly regulated by BC200 have been elucidated. This talk will present our initial work to characterize the structure and function of BC200. Knock-down of BC200 expression results in a dramatic loss of viability through growth arrest and induction of apoptosis; whereas BC200 overexpression had no discernible impact on cell growth or viability. A substantial decrease in BC200 expression was observed upon cell confluence, as well as drug induced cell cycle arrest in G1 or G2 but not S- or M-phases. Protein binding partners of BC200 have been identified through mass spectrometry approaches, as have potential cancer-specific RNA targets via qPCR arrays. Together the work presents compelling evidence that BC200 plays a central role in cancer cell survival and proliferation.

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March 28, 2017

Dr. Kristian Baker

Case Western Reserve University
Center for RNA Molecular Biology
Cleveland, Ohio, USA

"RNA Quality Control - Looking for Nonsense"

Work in the Baker lab is focused on understanding the molecular mechanisms underlying the recognition and rapid degradation of nonsense codon-containing mRNA in eukaryotes by the conserved, nonsense-mediate mRNA decay (NMD) pathway. We couple classical genetics and biochemistry with transcriptome-wide and proteomic approaches to elucidate how the cell detects these aberrant mRNAs and how the NMD machinery functions to rapidly clear them from the cell. Exciting new findings suggest that the NMD machinery directly interacts with prematurely terminating ribosomes and that this interaction is critical for targeting the mRNA to accelerated decay.

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February 15, 2017

Dr. Michael Stingl

University of Lethbridge
Department of Philosophy
Lethbridge, Alberta, Canada

"Ethical Arguments: Are They Aimed at Truth?"

The talk will start with two moral dilemmas to get us arguing about ethics.  Given how we in fact argue about ethics, it seems like we are in the pursuit of something we might want to call moral truth:  the truth about what we ought to do, or at least, ought not to do.  Is moral truth purely a matter of the internal coherence of our overall system of moral beliefs, from beliefs about particular cases all the way up to the most abstract and general of moral principles?  Or might moral belief systems be anchored in certain kinds of things that are naturally and biologically good, like empathetic caring, fairness and trust?  Might moral beliefs, in other words, be on the track of moral goods that are what they are, independently of how we might want to think and argue about them?

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January 30, 2017

Dr. Athan Zovoilis

University of Lethbridge
Department of Chemistry and Biochemistry
Lethbridge, Alberta, Canada

"Decoding the non-coding: The case of B2 SINE repeats"

Only 1-2% of our genome has protein-coding potential. The rest of the genome consists largely of repetitive DNA, with satellite DNA, retrotransposable elements, and DNA transposons accounting for ~50% of noncoding sequences. For much of the past few decades, these poorly conserved elements have been considered “junk DNA” — remnants of evolution and genetic parasites that proliferate without constraint of purifying selection. According to the ENCODE project however, >80% of noncoding DNA (including repetitive DNA) is developmentally transcribed into non-coding RNAs. It remains unknown whether these non-coding RNAs have a role in cell function and human disease. However, existing RNA sequencing and data analysis pipelines often ignore most of these RNAs or regard them as transcriptional noise and they filter out these RNAs from further analysis. This talk will present the case of a class of these RNAs, those derived by the mouse B2 SINE repeats, and the attempt to change the above approach to "transcriptional noise". I will elaborate on bioinformatics approaches I used to detect and study the function of these non-coding RNAs that until recently we have either ignored or have been unable to detect.

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