3MT Competition Winners

Graduate Studies

With only three minutes and one static slide, the following graduate students won the top prize in their respective year against a competitive field of participants representing the University's diverse field of academic disciplines.

These winners were granted an opportunity to compete at the Western 3MT Competition with a chance to move on to the National 3MT.

2020 Winner - Breanna Meek, Bioscience, Technology, & Public Policy

Integrate me one more time: ERVK integrase as a source of DNA damage in neurodegenrative disease

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease impacting brain and spinal cord motor neurons. Endogenous retroviruses are ancient viral elements in the human genome. Endogenous retrovirus-K (ERVK) integrase enzyme is expressed in affected ALS tissues. Integrase inserts viral DNA into the host genome by breaking host DNA and relying on cellular repair mechanisms to fix this damage. Failure to repair DNA damage can lead to necroptotic cell death and neurodegeneration. To study ERVK integrase-mediated DNA damage and necroptosis, I will insert ERVK integrase expression vectors into a variety of cell types, including stem cells for the generation of cerebral organoids. I will use Western blot and confocal imaging to identify the presence of ERVK integrase, DNA damage (γH2AX), engagement of DNA damage repair pathways (BRCA1, DNAPK, and PARP1), and ultimately necroptosis (p-MLKL). Understanding cellular effects of ERVK integrase-driven neurodegeneration may lead to future therapeutics for patients with ALS.

2019 Winner - Maire Josée Nadeau, Bioscience, Technology, & Public Policy

ERVK Intergrase Block Antiviral Immunity

Endogenous retrovirus-K (ERVK) is a group of retroviral elements in the human genome that are upregulated in the brains and spinal cords of patients with Amyotrophic lateral sclerosis (ALS), a neurodegenerative disease without a cure. A hallmark of ALS pathology includes DNA damage, a phenomenon known to be initiated by retroviral integrases (INs). Thus, I am investigating the role of the ERVK IN enzyme in ALS. My research shows that ERVK IN causes DNA damage and prevents antiviral IRF3 activity in astrocyte brain cells. I am further investigating how the cellular pathway leading to IRF3 activation is disrupted by ERVK IN. Lastly, I am repeating these experiments with the addition of integrase inhibitors to determine if ERVK IN-mediated cellular effects are reversed. As ERVK is known to be active in ALS, this gives hope that IN inhibitors can be repurposed as an effective treatment option.

2018 Winner - Dean Reddick, Bioscience, Technology, & Public Policy

A Simple Test To Increase Treatment Response of Breast Cancer

Tamoxifen is a very effective form of endocrine therapy for the treatment of Estrogen Receptor positive (ER+) breast cancers. However, approximately 50% of all patients develop a resistance to the drug. There are reports suggesting involvement of the PI3K/mTOR pathway in endocrine resistance and that N-myristoyltransferase (NMT) phosphorylation by mTOR may play a role. The overreaching goal of my research is to determine the potential role of NMT in endocrine therapy resistance development and to determine if NMT subcellular expression patterns can be used as a predictive biomarker. Several putative phosphorylation sites in NMT have been identified and mutated to alanine (phospho dead) or glutamic acid (phospho mimic). Various NMT mutants along with wild type (wt) NMT plasmids were prepared and expressed in ER+ breast cancer cells. Future studies are directed towards treating these cells with tamoxifen to investigate whether NMT phosphorylation by mTOR confers resistance to endocrine therapy.

2017 Winner - Aliraza Alidina, Development Practice: Indigenous Development

Fostering a Safe Space for Dialogue between Indigenous and Newcomer Communities

Winnipeg is experiencing an interesting period: it has a large Indigenous population, and an increasing newcomer population. The two communities – as diverse as they are – share a lot in common: a history of colonial encounter, socioeconomic challenges, and communal values. There is however, very little interaction between the two communities. This absence of interaction is due to a lack of knowledge, understanding and awareness about each other. As a result, this has pitted the two communities against each other. Hence, there is a need to create a safe space for dialogue. Community organizations (in the settlement sector) have a responsibility to institutionalize dialogue. It is of prime importance that newcomers understand the colonial history of Canada and some of its contemporary legacies, as well as basic awareness on the First peoples of this land. This is the essence of Truth and Reconciliation calls to action #93.

2016 Winner - Oluwayemisi Olugboji, Applied Computer Science & Society

Improving the Prognosis and Diagnosis of Chronic Kidney Disease Using Naive Bayes Algorithm

Big data represents a ground-breaking opportunity for healthcare industry to improve service quality. Clinical Decision Support will help the clinician answer clinical questions quickly when information is needed, especially if the learning method is built into the Electronic Health Record (EHR). This paper delineates how unstructured data can be mined from different point of care devices to improve the prognosis and diagnosis of Chronic Kidney Disease (CKD). This proposed mining system will scrape and analyze data from ubiquitous point of care devices and make predictions. This system will help predict potential events which may be symptoms of Kidney disease or a drug interaction that could lead to kidney problems. CKD is among the top ten leading causes of death in Canada according to Statistics Canada. This research will help clinicians in the areas of chronic disease management, prenatal patients monitoring, preventative medicine, and aggregation of medical information.

2015 Winner - Mamneet Manghera. Bioscience, Technology, & Public Policy

Silent No More: Augmented IFNy signaling re-activates Human Endogenous Retrovirus-K

Retroviral-derived sequences called human endogenous retroviruses (ERVs) comprise a large proportion of the human DNA. Re-activation of the youngest endogenous retrovirus, ERVK, has been implicated in the neuropathology of Amyotrophic Lateral Sclerosis (ALS). Unfortunately, the signals that re-activate ERVK remain unclear. ALS is marked by augmented levels of the pro-inflammatory cytokine Interferon-γ (IFNγ), which is a potent activator of HIV – another retrovirus. Using real-time polymerase chain reaction and western blot, we show for the first time that IFNγ enhances ERVK gene transcription, polyprotein expression, and promotes cleavage of the polyprotein into reverse transcriptase (RT) subunits in human astrocytic and neuronal cell lines. This coincides with an increase in cellular RT enzymatic activity. Fluorescent imaging further reveals markedly enhanced cytoplasmic, perinuclear, and nuclear RT staining in IFNγ stimulated cells. These newly established in vitro models of ERVK re-activation will permit further examination of ERVK biology in the context of neuroinflammatory disease.

2014 Winner - Matthew Turnbull, BioScience, Technology & Public Policy

In Silico modeling of the endogenous retrovirus K protease

The human genome is filled with ancient retrovirus-like elements called Human Endogenous Retroviruses. Most of these elements are inactive under normal conditions, but some endogenous retrovirus K family members are activated in inflammatory diseases. These genetic elements express classical retroviral proteins: polymerase, capsid and envelope proteins, as well as protease. Protease is essential for the maturation of structural viral proteins. Inhibition of ERVK protease may lead to amelioration of disease outcomes, as it does in Human Immunodeficiency Virus (HIV) infection. ERVK protease is poorly inhibited by drugs that target HIV protease; the discovery of new inhibitors is hampered by the lack of a published ERVK protease structure. An alignment of characterized retroviral proteases and prototypic ERVK proteases created using Geneious software was used to evaluate the suitability of ERVK protease for homology modeling. ERVK protease models will be used to predict in silico the efficacy of novel small molecule inhibitors.

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