MacEwan Open Journals (MacEwan University)
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Survival of the Fittest: Elucidating Fitness of Escherichia coli strains Lacking Pseudouridine Synthases
No full textThe ribosome is a fundamental component of gene expression, producing proteins from corresponding mRNA sequences. The ribosome is comprised largely of ribosomal RNA (rRNA), which is known to contain various nucleotide modifications. The most abundant of these modifications is pseudouridine, the 5-ribosyl isomer of uridine, whose isomerization is catalyzed by pseudouridine synthases. The peptidyltransferase center (PTC) of the E. coli ribosome contains 6 pseudouridines generated by four pseudouridine synthases.
The objective of this study is to examine the contributions of ribosomal pseudouridine synthases to bacterial fitness by characterizing growth phenotypes of knockout strains. Each of the four pseudouridine synthases acting on the ribosomal PTC were sequentially deleted from wild type E. coli, and the effects on cellular fitness were assessed using competition assays and growth curves in both minimal medium and in the presence of antibiotic. The competition assays revealed that each knockout strain (single, double, triple, and quadruple) exhibited a severely reduced fitness, as they were quickly outcompeted by the wildtype strain. The growth curves showed that certain pseudouridine synthases became more important under different stress conditions. In minimal media, it was found that RluB and RluF are more important than the alternative pseudouridine synthases in counteracting the effects of nutrient limitation, both with and without antibiotic present. Additionally, deleting RluE seemed to rescue the growth phenotype in the multiple knockouts. Together, these findings suggest that pseudouridines play different roles in ribosomal activity within the cell depending on the growth conditions, and provide selective advantages for E. coli when competing for limited resources
An analysis of mutational signatures in breast cancer among young women
No full textBACKGROUND. Approximately 7% of breast cancer cases are diagnosed among women 40 years of age or younger, and over 40% of all cancer diagnoses in this population are breast cancer. In 1969-2012, there was an increasing incidence of breast cancer among young (≤40 years) Canadian women, and in 1995-2006 there was also an increase in incidence of 3% and 1% among European women 20-29 years and 30-39 years respectively. Younger age is related to later stage at diagnosis, and worse outcomes even when controlling for disease stage and other prognostic features. The most aggressive tumour subtypes, human epidermal growth factor receptor 2 positive and triple-negative breast cancer have a higher prevalence among young women. Clinical and molecular differences between tumours diagnosed at different ages motivates study of differences in patterns of mutations at a genomic level. Mutational signatures are patterns in the type and three-nucleotide neighbourhood of somatic single-nucleotide variants across the exome, which may provide insight into the exposures and processes leading to carcinogenesis.
METHODS. Clinical and variant call data for 1098 breast cancer patients was taken from The Cancer Genome Atlas. Cases were separated into young (≤40 years) and old (>40 years) age groups, and the mutational load was found for each. The SomaticSignatures R package was used to determine the mutational spectrum of one young patient. This package will be used to construct mutational spectra for each age group, then decompose them into mutational signatures.
RESULTS. There were 91 and 951 patients in the young and old categories respectively. The young group had a median mutational load of 166.5 mutations, slightly less than the median of 198 in the older group. The mutational spectrum showed a high frequency of TCA>TTA and TCT>TTT variants, which is similar to the previously identified Signature 2, and similarly a high frequency of TCA>TGA and TCT>TGT transitions which resembles Signature 13. These two signatures are commonly found in the same tumour, and are thought to be caused by cytidine deaminase activity of AID/APOBEC proteins.
CONCLUSIONS. Patterns in a mutational spectrum suggest that Signatures 2 and 13 may be present in at least one young breast cancer tumour, but this approach should be continued to confirm this hypothesis. Further research should be conducted with a larger sample of young breast cancer patients with known exposures to risk factors.
*Indicates superviso
Regulating gene expression through targeted RNA modification
No full textPseudouridylation refers to the isomerization of uridine to pseudouridine in RNA and is catalyzed by enzymes known as pseudouridine synthases. In eukaryotes, pseudouridylation of rRNA is primarily directed by a complex of proteins and a box H/ACA guide RNA. The guide RNA specifies a target by forming transient base pair interactions on either side of the target uridine, although other standalone pseudouridine synthases may employ different targeting mechanisms.
With this project, we aim to modify naturally occurring guide RNAs to allow for specific targeting in a location different from the original. Pseudouridylation of a premature stop codon in mRNA results in translational readthrough and production of a functional protein. Here, we utilize the CUP1 gene from baker’s yeast as a model gene to be targeted by pseudouridylation that enables survival in the presence of high copper concentrations.
First, we have generated and purified two guide RNAs never previously worked with in our lab to test their effectiveness at targeting a specific uridine. Also, the proteins associating with these H/ACA guide RNAs have been expressed and purified for biochemical investigations. Second, a premature stop codon was introduced at the ninth codon of the CUP1 gene (Q9UAA). As a control to mimic the presence of a pseudouridylated stop codon, we have generated the mutants cup1p(Q9S) and cup1p(Q9T) mimicking readthrough of the premature stop codon and tested their ability to chelate copper in vivo. Interestingly, these experiments revealed that not all premature stop codons can be rescued by pseudouridylation. Current work focuses on the insertion of test sequences harboring premature termination codons upstream of CUP1. These test sequences are predicted to be targeted by known pseudouridine synthases.
Ultimately, this experimental system will identify which sequences harboring premature stop codons can be targeted by pseudouridylation to re-activate gene expression. This new system to regulate gene expression has applications in bioengineering and possibly the treatment of inherited diseases resulting from mutations that cause premature stop codons.
*Indicates presente
Creating A Fitting Algorithm for Exoplanet Detection
No full textThe purpose of this project is to create an accurate fitting function for transiting stars. Data from these transiting stars will ultimately be used to identify new exoplanets. It is very apparent that a fitting function that addresses multiple environmental parameters affecting brightness measurements is needed as exoplanet identification can be a cumbersome and time consuming process. Utilising computer code will streamline the process of exoplanet identification and can then allow researchers to focus their energies solely on data collection.
It should be duly noted that in order to collect data from transiting stars; one can use amateur equipment but, for the sake of maximum accuracy; a high powered telescope would be more suitable (“Exoplanet Transit Parameters”, 2008). Previous students at MacEwan that collected transiting star data utilised the Athabasca University Robotic Telescope (AURT) (“Defining the Transit Method”, 2017). This telescope requires booking periods thus, in order to maximize utility and efficiency; more energy should be spent on data collection and result analysis.
The current state of exoplanet discovery is both innovative and exciting. In fact in February of 2017, a team of astronomers at the University of Liege in Belgium discovered four more Earth-sized exoplanets (bringing the total up to seven) orbiting Trappist-1 which is a star that is classified as an ultracool dwarf (“Astronomers Discover”, 2017). Another discovery would be that of Proxima b, the exoplanet that is closest to our solar system (“An Earth-like Atmosphere”, 2017). Astronomers are currently debating whether or not Proxima b will be able to sustain life. Thus, it can be shown that exoplanet discovery and analysis yields results and is vital for our understanding of the universe.
Works Cited
Garner, R. (2017, July 31). An Earth-like Atmosphere May Not Survive Proxima b’s Orbit. Retrieved January 21, 2018, from https://www.nasa.gov/feature/goddard/2017/an-earth-like- atmosphere-may-not-survive-proxima-b-s-orbit
Kopchuk, T. (2017, September 22). Defining the Transit Method Observation Limits of the Athabasca University Robotic Telescope. Retrieved January 8, 2018. Pejcha, O. (2008, September 7). Exoplanet transit parameters from amateur-astronomers observations. Retrieved January 16, 2018.
Scharf, C. A. (2012, January 20). An Abundance of Exoplanets Changes our Universe. Retrieved January 21, 2018, from https://blogs.scientificamerican.com/life-unbounded/an- abundance-of-exoplanets-changes-our-universe/
*Indicates superviso
Perception of Recreational Opportunities on a Campus to Increase Wellness
No full textUniversities strive to enhance the student experience and promote student success. A major contributor to student success is the development of wellness, defined as the state of being in good health, especially as an actively pursued goal. Positive subjective wellness is achieved when individuals actively engage leisure activities to increase wellness. In conjunction with the Lethbridge Campus Ecology Project, the purpose of the study was to investigate undergraduate students’ use of campus green space to increase wellness and manage perceived stress. To enhance wellness in practice, it is essential to determine not only what the students want, but also what types of outdoor leisure additions they would use. A survey was generated to explore students’ perception of leisure opportunities on campus and investigate what type of outdoor recreation students would use to enhance their wellness. Information gathered from responses will provide insight on what implementations would be utilized to increase greater wellness and reduce stress in students. It is hypothesized that outdoor leisure opportunities will be associated with an increase in subjective student wellness. Additionally, it is expected that females and males will differ significantly in their choices for wellness enhancement strategies
An analysis of mutational signatures in breast cancer among young women
No full textBACKGROUND Approximately 7% of breast cancer cases are diagnosed among women 40 years of age or younger, and over 40% of all cancer diagnoses in this population are breast cancer. In 1969-2012, there was an increasing incidence of breast cancer among young (≤40 years) Canadian women, and in 1995-2006 there was also an increase in incidence of 3% and 1% among European women 20-29 years and 30-39 years respectively. Younger age is related to later stage at diagnosis, and worse outcomes even when controlling for disease stage and other prognostic features. The most aggressive tumour subtypes, human epidermal growth factor receptor 2 positive and triple-negative breast cancer have a higher prevalence among young women. Clinical and molecular differences between tumours diagnosed at different ages motivates study of differences in patterns of mutations at a genomic level. Mutational signatures are patterns in the type and three-nucleotide neighbourhood of somatic single-nucleotide variants across the exome, which may provide insight into the exposures and processes leading to carcinogenesis.
METHODS Clinical and variant call data for 1098 breast cancer patients was taken from The Cancer Genome Atlas. Cases were separated into young (≤40 years) and old (>40 years) age groups, and the mutational load was found for each. The SomaticSignatures R package was used to determine the mutational spectrum of one young patient. This package will be used to construct mutational spectra for each age group, then decompose them into mutational signatures.
RESULTS There were 91 and 951 patients in the young and old categories respectively. The young group had a median mutational load of 166.5 mutations, slightly less than the median of 198 in the older group. The mutational spectrum showed a high frequency of TCA>TTA and TCT>TTT variants, which is similar to the previously identified Signature 2, and similarly a high frequency of TCA>TGA and TCT>TGT transitions which resembles Signature 13. These two signatures are commonly found in the same tumour, and are thought to be caused by cytidine deaminase activity of AID/APOBEC proteins.
CONCLUSIONS Patterns in a mutational spectrum suggest that Signatures 2 and 13 may be present in at least one young breast cancer tumour, but this approach should be continued to confirm this hypothesis. Further research should be conducted with a larger sample of young breast cancer patients with known exposures to risk factors
Modelling Variations in Solar Irradiance
No full textThe sun is the main source of energy for the Earth, and governs most atmospheric, biological, and environmental processes. Due to fluctuating composition, thickness, and pollution, solar radiation can be scattered or absorbed in the atmosphere affecting the amount received by Earth’s surface as these interactions vary. Solar irradiance is the total amount of radiation reaching Earth’s surface, in watts per square meter, from the sun. Irradiance can be measured with a pyranometer, and is governed by the solar constant, atmospheric thickness, atmospheric composition, and beam dilution. In this project we have modeled the solar irradiance expected from a plane-parallel atmosphere to determine the sensitivity of the PYR-BTA Vernier Pyranometer to variations in atmospheric transparency with the intent to quantify pollution levels in urban areas. We used the solar irradiance data captured from MacEwan University to model the partial solar eclipse of August 21, 2017
Using 1H NMR Spectroscopy to Compare Urinary Metabolites of Stroke and Spinal Cord Injury Patients Before and After Neurorehabilitation
No full textBackground: Rehabilitation represents the primary approach to promote long-term functional recovery after neurological injury. There is an urgent need to improve the effectiveness of rehabilitation therapies to optimize the potential for recovery in an individual. Precision medicine approaches using modern ‘omics’ techniques represent vital prerequisites in stratifying individual patients with neurological injury to their optimal rehabilitation program. Metabolomics research from our laboratory has demonstrated that metabolite levels in urine detected by NMR spectroscopy serve as reliable prognostic markers for neurological injury. This study aims to determine if a proton NMR-based quantitative metabolic profiling approach can identify novel biomarkers in clinically accessible biofluids that are indicative of both the repair processes and treatment efficacy following neurorehabilitation from stroke and spinal cord injury. The main hypotheses of this study are (a) that each of the neurological conditions will yield changes in the metabolic profiles that can be correlated to the extent of recovery of a patient and (b) that biological pathway analysis will provide an insight into the mechanisms behind the repair process. These techniques will provide a greater understanding of the biochemical processes that mediate neural repair in the central nervous system for clinical application.
Methods: Patients with stroke and spinal cord injury (n≥14 per group and sex) were recruited through the Foothills Medical Centre in Calgary, Alberta. Urine samples were collected from patients within 48-72 hours of injury and again at 6-months post-injury, following neurorehabilitation. A 700MHz Bruker Avance III HD NMR spectrometer located at the Canadian Centre for Behavioural Neuroscience was used to acquire the metabolic profiles of urine samples pre- and post-neurorehabilitation. Multivariate statistical and biomarker analysis tests were used to determine changes in the metabolic fingerprint which can potentially be linked to clinical outcomes.
Impact: Within the rehabilitation field there is an urgent need to generate evidence-based therapies and validate existing ones. Metabolomic analysis will provide a time- and cost- effective method to identify optimal rehabilitation therapies based on an individual’s impairments, through translational biomarker discovery. This personalized medicine approach offers a new strategy to evaluate and improve the efficacy of neurorehabilitation strategies for stroke and spinal cord injury patients.
*Indicates presente
Left Cerebellar Transcranial Direct Current Stimulation Facilitates the Onset of Inhibition of Return
No full textOver the past 20 years our knowledge of functional role of the cerebellum has evolved from that of a structure strictly involved in coordinating motor outputs, to one that is also heavily engaged in cognitive functions, including attention. Specifically, previous patient work indicates that cerebellar damage slows rapid shifts of reflexive covert (i.e. without moving your eyes) attention, as well as the onset of inhibition of return (IOR). In addition, recent fMRI studies suggest that the left lateral cerebellum may play an important role in covert attention through its connections with the frontoparietal attention network in the right cerebral hemisphere.In the current study we further examined the role of cerebellum in covert attention using transcranial direct current stimulation (tDCS) – a non-invasive brain stimulation technique – to in which a weak electrical current is applied to electrodes on the scalp to induce changes in baseline neural activity in the underlying cortex. Participants (n=23) completed a reflexive covert attention task using non-predictive peripheral cues and stimulus onset asynchronies (SOAs) of 50, 100, 300, and 600ms before, during, and after either anodal (+), cathodal (-), or sham tDCS applied to the left cerebellum (2mA for 20min). Results indicated that active tDCS stimulation facilitated the onset of IOR at the longest SOA compared to sham stimulation. When combined with recent patient and fMRI data, our results provide further converging evidence that the left lateral cerebellum plays an important role in reflexive covert visual attention.
Discipline: Psychology (Honours)
Faculty Mentor: Dr. Christopher Strieme
Stratigraphy of the Western Arctic Gateway-SWAG
No full textAs carbon dioxide levels begin to rise and temperatures continue to increase due to human impacts, we are beginning to see areas in the Arctic and the Antarctic becoming more accessible with reduced sea ice cover. The Northwest Passage is becoming increasingly important due to its increased interest for ship navigation and mining operations. Understanding how deglaciation occurred in these areas will give us better insight on how future warming trends will affect the Northwest Passage. A sediment core was recently recovered from M\u27Clure Strait, western Northwest Passage. Investigation of this core using litho- and bio-stratigraphy and benthic microfossils as a proxy for past environmental conditions will give us a better understanding of how and when deglaciation occurred and the response of the marine system. This study focuses on the litho- and biostratigraphic descriptions of the core to explain the timing and style of glacial retreat in the region.
Discipline: Biological Sciences
Faculty Mentor: Dr. Mark Furz