2A18 Abstracts 2019

Aristone, Chelsea, and Eckert, Lucas-Habitat Preference and Resource Partitioning in Overwintering and Early-Spring Birds (Dr. Chad Harvey)

This study investigated habitat usage of overwintering and early-arriving spring bird populations in the McMaster Forest in Hamilton,  Ontario,  Canada. Specifically,  the study examined habitat and tree species preference among various bird species,  providing insight into habitat usage,  resource partitioning,  and ecological interactions. Data collection took place in the McMaster Forest over a two-week span in March 2019. Observations were made for all active tree-foraging birds. The bird species,  tree species,  location on tree,  and forest type were recorded. Eighteen sample sites were visited over the two-week period,  covering a variety of forest types. The data was grouped based on similar bird species,  and groups were analyzed using pairwise Fisher’s exact tests and a Holm-Bonferroni correction. Analysis of the data revealed that bird species displayed significantly different (p<0.05) preferences in tree species,  tree section,  and forest type. These results indicate the presence of resource partitioning and habitat preference in the McMaster Forest. Bird species displayed different preferences for tree species and section,  decreasing interspecific competition and allowing the bird populations to maximize the use of the resources provided by the forest. This decrease of competition and fulfilment of niche space can be seen on a larger scale through the different habitat preferences displayed by bird species. Results from ecological studies such as this are quite valuable,  not only to gain a deeper understanding of local flora and fauna but also through practical applications such as determining the impact of humans and invasive species,  as well as possibly improving conservation efforts. 

Au-Yeung, Christy, and Ahmed, Maisha-A comprehensive review and mathematical model of multisite phosphorylation of the Alzheimer’s-associated tau protein  (Dr. George Dragomir)

Alzheimer’s disease (AD) is the most common cause of dementia,  accounting for 60-80% of dementia cases. A hallmark of AD is the accumulation of tau proteins in the hyperphosphorylated state.  These proteins normally play an integral role in providing neuron support and facilitate molecular transport across cellular components as a microtubule-associated protein.  When hyperphosporylated,  tau proteins become misregulated,  self-aggregate and form toxic neurofibrillary tangles (NFT). These NFTs are hallmark intracellular inclusions that form in the brains of Alzheimer’s patients,  and are toxic to neurons as they disrupt intracellular functions,  decrease synaptic ability,  and lead to apoptosis. A literature review was conducted on the factors leading to tau hyperphosphorylation.  Contributing factors include the disrupted protein functioning of cyclin-dependent kinase 5 (CDK5),  glycogen synthase kinase-3 (GSK3) and protein phosphatase 2 (PP2A). 

We have created a probability-based mathematical model,  that is able to predict the short-term kinetics of the phosphorylation of amino acids Serine 396 and Serine on the tau proteins,  over time. This particular amino acid residue region has been of interest in recent years due to the potential for the use of antibody-mediated therapies that target this protein region in patients with AD. 

Barber, Gemma, and Tertigas, Dominique-The Development of Antibiotic-Resistant Bacteria through Exposure to Increasing Doses of Streptomycin and Doxycycline (Russ Ellis)

Antibiotic resistance is one of the most pressing issues in the medical field today. It is important to understand the development of bacterial resistance in order to implement more effective preventative measures against antibiotic-resistant bacteria. This Enrichment Project investigated selective antibiotic pressures leading to antibiotic resistance by replicating components of a study by Oz et al. (2014). The change in minimum inhibitory concentration (MIC) for each antibiotic was determined as the bacteria became increasingly resistant to streptomycin and doxycycline.

Initial MIC values were determined in 96-well plates consisting of positive and negative controls,  and treatments with either antibiotic. A wild type strain of Escherichia coli was selected as the test bacteria due to its susceptibility to both treatments. After incubation,  bacteria were isolated from the well at the predetermined MIC value and grown overnight in nutrient broth before continued treatment at the next generation of MIC. Outcomes compared the rate at which antibiotic resistance occurred for each treatment. 

E. coli progressively grew at higher concentrations of each antibiotic,  due to increased resistance. The mechanisms of action for both treatments are similar,  but the fastest rate of antibiotic resistance was observed for streptomycin,  with doxycycline exhibiting a slower rate,  potentially due to small differences in target domains.

This research is important as knowing the rate at which bacteria become resistant to certain antibiotics is essential for determining appropriate concentrations and timelines for antibiotic treatments to minimize bacterial resistance.

Dogar, Maha, and Dwivedi, Abhigyan-Overcoming antibiotic resistance strategies Pseudomonas aeruginosa with novel antibiotic discoveries (Dr. Rosa da Silva)

Antibiotic efficacy has experienced a decline due to the evolution of resistant bacteria. Some bacteria are resistant to all known antibiotics,  and as such can be fatal. The objective of this literature review will be to explore the mechanisms of antibiotic resistance of the biofilm-producing bacteria Pseudomonas aeruginosa,  a pathogen that causes mortality and morbidity in immunocompromised patients. P. aeruginosa resistance mechanisms can be divided into intrinsic,  acquired,  and adaptive resistance,  the latter being the focus of this review. Adaptive resistance is achieved through the formations of biofilms that serves as a multifactorial means of resistance,  thereby limiting access of antibiotics to the pathogen of interest. While many approaches to solve this crisis will be explored,  our focus will be on nitric oxide concurrently delivered with antibiotics to disperse the biofilm and allow the antibiotics to penetrate the bacteria with greater efficacy. Multidrug resistance occurs in steps as resistance develops to each individual drug; therefore,  if a pathogen is caught in early stages of drug resistance,  other antibiotics can be used to eliminate it from the population preventing it from forming multidrug resistance. Understanding the biological mechanisms of antibiotics resistance is crucial for the development of new pharmaceuticals and policies that can save thousands of lives. 

Froelich, Juliette, and Pirbay, Shama-Analyzing the Composition of Necromone Solutions Intended as Pest Deterrents  (Dr. Chad Harvey)

Harmonia axyridis are known pests in the wine industry,  as they secrete 2-isopropyl-3-methoxypyrazine (IPMP) when stressed,  a compound with an unpleasant taste and odour. When H. axyridis secrete IPMP on grapes,  it negatively impacts wine produced from the grapes. Upon death,  the beetles also release necromones,  a class of fatty acid pheromones,  which alert other beetles of danger and to avoid an area. To evaluate the potential of necromones as pest deterrents,  we proposed an experiment where H. axyridis bodies are placed in 95% ethanol for five days to create necromone solutions,  and the presence of the compounds is confirmed through GC-FID-MS. The fatty acid necromones are derivatized with 8% methanolic hydrochloric acid to form fatty acid methyl esters (FAMEs),  while IPMP does not undergo derivatization. Sodium bicarbonate neutralizes any remaining acid,  and the FAMEs and IPMP are extracted with hexane. C18D35 is spiked into each solution as an internal standard,  and 1 ‘_L of solution is injected into the GC-FID-MS. To estimate the presence of the analytes,  the signal peaks are compared to those of pure standard solutions to determine the presence of the analytes. The presence of the necromones in these solutions would indicate the potential of the solutions as pest deterrents,  while the presence of IPMP would negate the purpose of the necromones as the quality of the wine would still be compromised. Determining the potential of necromone solutions as pest deterrents would benefit the wine industry by contributing to the preservation of wine taste and odour.

Hum, William, and Stokes, Alun-Novel Visualisations of Prime Numbers  (Dr. George Dragomir)

Prime numbers are one of the oldest and most fundamental objects in mathematics,  as they compose the basis for the construction of numbers themselves. Understanding their properties and behaviour can be illuminating both in terms of their pure number theoretic roots,  as well as the vast number of fields predicated on them. Prime numbers are used in many aspects of modern life – one of the most prominent of which being the cryptographic systems that allow the existence of a large part of the internet. Despite their importance,  there is a surprising amount that is not understood about this set of numbers. As such,  they require further study. One method of investigating mathematical relationships is using visualisations. Mathematical visualisation is a method that generates images that may elucidate patterns. Various properties of prime numbers can be investigated using computer-assisted visualisations. Two of the most famous prime number visualisations are the Ulam spiral and Klauber triangle. Our project investigates novel visualisations of the prime numbers through the manipulation of structure,  and the different integer sequences within them. The intention of this project is to produce and investigate visualisations that may uncover patterns within the distribution of the primes – to the ultimate end of better understanding this set of numbers. The irrational linear flow on the torus was used to plot the prime numbers and explore possible geometric or numerical relationships. This model has possible wide-reaching consequences that may add to numerous fields of study – both mathematical or otherwise.

Hurtarte, Milena, and Tywonek, Kasia -Literature Review of CD19 specific CAR-T immunotherapy for B cell Acute Lymphoblastic Leukemia (Dr. Maikel Rheinstadter)

This literature review examines the newly FDA approved target therapy for cancer treatment; CAR T CD19 immunotherapy. This therapy is used to treat B-cell acute lymphoblastic leukemia (B-ALL). B-ALL is an aggressive form of cancer which does not respond well to chemotherapy or surgery. The therapy uses modified cells from the patient’s own immune system and engineers a receptor which will recognize the cancer cells. In this specific therapy,  the receptor is engineered to recognize the CD19 ligand on the tumour cells. Using this highly individualized treatment,  cancers with a high rate of metastasis can be mitigated by the targeted nature of this therapy. The literature review aims to summarize the process through which CAR T was developed from inception to FDA approval. This was achieved by using databases such as Pubmed and Google Scholar to retrieve articles related to the innovative research which produced the current therapy. Clinical trials from respective stages of development were also detailed and summarized. The brand Yescarta was FDA approved October 18,  2018 for the treatment of adults with B-cell lymphoma and leukemias. The material examined in this literature is up to date until March 2019,  examining the mechanisms and management of CAR T-cell toxicity experiences by patients undergoing treatment. 

To conclude,  the aim of this review is to outline the discovery process of CAR-T CD19 therapy from a biochemical and healthcare perspective as well as future avenues for therapy development. 

Kim, Kate, and Yang, Jasmine-Chemical Comparison of Ginseng and Advil to Analyze Similarities and Differences Between Natural Remedies and Western Medicine (Russ Ellis)

For centuries,  medicinal plants have been used as natural remedies to provide relief to ailments,  similar to that provided by current Western medicine. However,  the legitimacy of natural remedies is often questioned by the general public due to an apparent lack of scientific substantiation. 

The scope of this project is to compare natural and synthetic medicine aimed at reducing inflammation. The medicinal plant Ginseng and its equivalent Western medicine propanoic acid,  sold under the brand name Advil,  was investigated. 

Ginsenosides,  the active ingredient of Ginseng,  were extracted from Ginseng plant roots through dissolution in isopropanol,  and concentrated through rotary vaporization. Ibuprofen,  the active ingredient of Advil,  was extracted through dissolution in ethanol. The presence of ibuprofen and ginsenosides in each solvent was confirmed through thin-layer chromatography staining methods: UV and p-Anisaldehyde sulfuric acid stains. After confirming the presence of the two compounds,  the chemical structures were analyzed for similarities and differences using liquid chromatography and tandem mass spectrometry on the ginsenoside sample and using literature values for ibuprofen. 

The ginsenosides,  Rb1,  Rb2,  Re,  Rg1,  Rd,  Rb3,  and Rc,  were identified in the isopropanol solution. Through comparing data,  it was found that the chemical compositions of the two compounds differ greatly. Tandem mass spectroscopy data of ginsenosides and ibuprofen did not show any similarity with the peaks,  demonstrating completely different chemical structures. 

Thus,  the results of the study suggested that ginseng should be avoided to be used as the replacement for ibuprofen to reduce inflammation as a natural remedy. 

Mortazavi, Amir-The Evolutionary Significance of Sleeping and Dreaming  (Dr. Chad Harvey)

We have evolved to sleep one third of our lives. However,  when we sleep,  we lose the ability to gather food,  reproduce,  fulfill our social needs and we are more vulnerable to predation. Additionally,  we spend a quarter of this time dreaming; where most of our body is paralyzed and our minds are spending plenty of energy to hallucinate and suffer from a psychotic experience. Therefore,  in an evolutionary perspective,  we would have not been selected by nature if sleep was not absolutely vital to our survival and dreaming was merely an epiphenomenal property of sleeping.

This literature review,  we attempt to explore the vital roles of sleeping and dreaming in a physiological level. This study explains the mental processes,  such as memory consolidation,  attention and learning,  emotion control,  creativity ,  etc. that are directly related to sleeping and dreaming. Moreover,  lack of sleep is one of the major causes of many disorders and diseases,  such as Alzheimer’s disease (AD),  cardiovascular disease (CVD),  cancer and psychological disorders. 

We have used studies about sleeping and dreaming phenomenology,  lack of sleep pathology and significance of sleep in healthy brain function. 

This study identifies sleep as the main pillar of well-being and dreaming as a crucial component of it. Humans are the only species that intentionally deprive themselves from sleep and this is one of the major troubling problems of the 21st century.

Paliwal, Ishita, and Wang, Peipei-Mathematical determination of the most influential protein-protein interactions for the treatment of Cerebral Sinus Venous Thrombosis (Dr. George Dragomir)

Cerebral sinus venous thrombosis (CSVT) is a rare form of stroke with significant morbidity and mortality rates in young patients. Current treatments attempt to suppress blood clot formation through the use of anticoagulants. However,  their administration is controversial due to the presence of a hemorrhagic element in 40% of CSVT cases. A leading cause of CSVT is caused by malfunctions in the proteins in the termination phase of the blood coagulation cascade. Extensive research has assessed the effects of isolated protein-protein interactions (PPIs) with thrombin in the coagulation cascade. However,  the proteins involved in thrombin activity form a complex regulatory network; identifying the most influential PPI could improve the target selection process of drugs for CSVT. This work proposes a stochastic model that estimates the impact of the PPIs of 14 regulatory proteins on clotting activity causing CSVT. Based on known relationships between thrombin and regulatory proteins,  a directed network was designed,  and a Markov chain approach was employed to assign quantitative values to different PPIs within the coagulation cascade. Results show that factor Xa has the greatest value,  and thus the greatest amount of influence,  for the first four minutes post-clotting stimulus. However,  Protein S has the highest influence for the remainder of the clotting process. This suggests that the development of Xa inhibitors and Protein S activators has vast potential in drug discovery for CSVT. By modifying the PPIs that are investigated within the coagulation cascade,  this model can be expanded to study other types of thrombosis. 

Pollinzi, Angela, and Tu, Megan-The Effect of Habitat on the Incidence of Agrilus Planipennis in the McMaster Forest  (Dr. Chad Harvey)

The Emerald Ash Borer (Agrilus planipennis Fairmaire) is an invasive species that has invaded much of the temperature North America from China and Korea (National Resources Canada,  2013). These beetles are highly destructive,  as they feed on the phloem of ash trees,  often resulting in significant defoliation and tree death. Thus,  they pose a threat to the diversity of invaded ecosystems,  causing soil erosion,  altered solar exposure and increased water temperatures in adjacent streams. Furthermore,  ash trees are often used to provide shade in urban areas,  resulting in an increase in property value. This study revisits research performed by Kyra Simone (2017) and explores the incidence level of the Emerald Ash Borer in the McMaster Forest. Using stratified random sampling techniques and a set of visual assessments,  we determined which ash trees are infected,  and assessed the degree of bark splitting on a 5-point scale in order to determine the state of tree health. In this study,  it was determined that an increase in woodpecker damage and Emerald Asher Borer incidence is correlated to specific ecological regions of the forest. These results offer a method to analogously evaluate Emerald Ash Borer infestations in other areas of Southern Ontario and determine effective ways to reduce the level of invasion.

Reintjes, Caitlin, and Tugg, Yona-Considerations for Chemotherapy Treatment of Patients with Platinum-Resistant High Grade Serous Ovarian Cancer (Dr. Rosa da Silva)

Ovarian cancer is considered to be the most fatal type of any gynecological cancer. Prognosis for the disease is poor,  with a median survival of only thirty-two months following diagnosis and a five-year survival rate of only 39%. Many of the most lethal ovarian cancer cases are classified as part of the high-grade serous ovarian cancer (HGSOC) subtype,  which is the most aggressive form of the disease. The primary issue with regards to treatment is that around 30% of patients will develop a resistance to forms of platinum chemotherapy,  which is the main method of treatment. This suggests that a one-size fits all approach cannot be taken to treat ovarian cancer and that further analysis must be done to understand how to treat those patients who present with platinum resistance.

This literature review examines the mutations within two susceptible loci,  specifically the p53 and BRCA1/2 genes,  in order to understand how platinum resistance develops and why it is present in some patients. The objective is to understand the underlying genetic mechanisms affecting platinum resistance,  identify the biomarkers associated with those mechanisms,  and provide alternative methods for approaching ovarian cancer treatment on an individual scale.

Schimmer, Pamela , and Sacka, Katarina-Mathematically Modelling Earth’s Magnetic Pole Reversals  (Dr. George Dragomir)

The Earth has an intrinsic magnetic field,  which is generated by the spinning of the iron core and creates a magnetic North and South pole. As observed through changing in the magnetic orientation of rocks on Earth’s spreading sea floor,  the Earth’s magnetic poles have reversed multiple times throughout history. The time between each complete geomagnetic pole reversal is estimated to span anywhere between ten thousand and ten million years,  suggesting that the process is complex and seemingly stochastic. Understanding when and why this phenomenon occurs is crucial since the reversal process causes significant weakening of the field leaving the Earth susceptible to harm from solar radiation. While the total effect on human society is not entirely clear,  a reversal in field would impact other animals,  interfering with their migration patterns. In an attempt to understand the underlying mechanisms of geomagnetic pole reversals and to predict their occurrence,  various mathematical models have been developed. Of note,  the Rikitake model investigates the mathematical and physical connection between electromagnetic systems known as coupled dynamo disks,  and Earth’s own dynamic magnetic system. In addition to the Rikitake model,  variations of Poisson distributions and statistical models have been investigated. Through literature analysis and our own implementation of the Rikitake model,  we hope to further understand the connection between electromagnetic processes and geophysical processes. 

Scott, Sarah-A web-based platform that increases accessible communication of drug discovery research for both the general public and scientific communities (Dr. Rosa da Silva)

Annually,  the ISCI2A18 cohort completes an Enrichment Project. Abstracts are posted online and presentations are given to share information with the students of the current year,  however,  prospective students may not access all this information. Given the advantages of the current digital age,  the creation of an online platform will allow for information exchange among each year,  as well as with students of future years. This platform has the potential to consistently grow,  be updated,  and provide benefits to all cohorts. 

The 2021 cohort will therefore create and launch a website platform that will be designated as an information exchange between students who are engaged in the ISCI2A18 Enrichment Projects relating to the Drug Discovery module. As an open access website,  this platform,  The Drug Discovery Exchange,  will have the potential to benefit other students in the Faculty of Science and the broader McMaster community as a whole. 

The website launch will showcase the research of 6 groups,  containing information in plaintext and scientific terms. The digital platform will be designed to be accessible and catered towards today’s lay audience,  with information concisely summarized and accompanied by audio and visual aids. 

The Drug Discovery Exchange has the potential to improve science communication and elevate the visibility of the scientific Drug Discovery community. By encouraging the sharing of information between the scientific community and general public,  individuals with or without experience in the field are able to remain informed and engaged,  and potentially contribute to the open access website.

Scott, Sarah, and Singh, Jalen-The Use of rAAV2 and Potential Future Application of CRISPR-CAS9 in the Treatment of Patients with Leber Congenital Amaurosis Type II (Dr. Rosa Da Silva)

This comprehensive literature review evaluates the current status of the use of rAAV2 and CRISPR-Cas9 gene therapy techniques in the treatment of Leber Congenital Amaurosis Type II (LCA2). The rAAV2 approach is a new technique that has only recently been approved for use in LCA2 treatments,  and research studies are few and disconnected. CRISPR-Cas9 is a technique currently under investigation as a potential future treatment of LCA2. This review serves to connect information from multiple studies to provide a comprehensive outline of the disease mechanisms that underlie LCA2,  the history of gene therapy and rAAV2,  the mechanism of rAAV2 use in LCA2,  as well as potential future advancements and use of CRISPR-Cas9 in the treatment of this disease. The obtained information will be collated onto a website platform,  and will be communicated in a manner that is accessible as both plain text and scientific text,  with suitable accompanying audio/visual components.

This paper reviewed primary sources to examine the mechanism of action of rAAV2 on LCA2,  as well as results,  safety,  and efficacy in the treatment in human patients. These papers,  published between 2012-2019,  all conclude that gene therapy in the form of rAAV2 is both safe and substantially effective in the treatment of LCA2. This research also provides insight into alternative treatment methods for other types of LCA.

Somani, Armaan-Mathematical View on the Shortcomings of the Standard Model of Particle Physics (Dr. George Dragomir)

A theory to explain all the physical aspects of the universe has been sought after for centuries,  as a result of the pursuit of knowledge and technological advancement. Several decades ago,  a quantum field theory called the Standard Model of particle physics was developed. The Standard Model is the most established candidate for a theory of everything; it has demonstrated huge successes in predicting experimental outcomes. However,  quantum field theories do not currently account for general relativity. The current Standard Model is unable to explain certain known phenomena,  such as gravity,  dark matter,  dark energy,  and matter-antimatter asymmetry. This study analyzes these major shortcomings from a mathematical perspective. The postulates of the Standard Model are compared with experimental research to demonstrate mathematical discrepancies that result in these shortcomings. We conclude that the Standard Model,  in its current form,  is inadequate to be a theory of everything. Explaining these phenomena and bridging the gap between quantum field theory and general relativity would allow the Standard Model to become a theory of everything. This study serves as a prerequisite to understanding or creating potential solutions to the Standard Model’s shortcomings. The development of a theory of everything would allow for unprecedented technological and scientific developments. 

Weiland, Lelia-Mapping Glacial Moraines in the Cordillera Blanca, Peru  (Dr. Carolyn Eyles)

The purpose of this project is to investigate the form of moraines in the Cordillera Blanca,  Peru. Specifically,  moraines that impound glacial lakes will be examined as these have the potential to fail and produce glacial lake outburst floods. These moraines have an unstable structure and their associated glacial lakes are rimmed with melting glaciers prone to avalanching.  This combination of factors generates the potential for failure or overtopping of the lake dam and flow of water downslope. The city of Huaraz lies at the confluence of several valleys,  each of which hosts a moraine dammed glacial lake. This creates a serious problem as a glacial lake outburst flood has the potential to flood the entire city,  causing damage and loss of life. 

Using Google Earth data and images from previously glaciated valleys dissecting the Cordillera Blanca,  a selected number of these moraines were studied and analyzed using ArcGIS. The elevation,  height,  and width of individual moraines was delineated and recorded. Shapefiles were created from this information and used to annotate a map of the area. 

This information will be useful to future studies,  as it allows visualization of the variation in moraine location,  form,  and size and provides easy access to encoded data. Additionally,  this study allows comparison of the form of moraines in different regions of the Cordillera Blanca and a better understanding of the potential stability of these moraines. This in turn will allow prediction of possible future glacial lake outburst floods,  potentially saving many lives. 

Wilberforce, Maggie-Graphic Mathematical Modelling of Calcium Binding Dependent Vesicle Exocytosis in the Presynaptic Terminal of a Central Synapse (Dr. George Dragomir)

A fundamental aspect of neuroscience is the understanding of the chemical synapse and its function. To relay electrical signals from neuron to neuron,  synaptic vesicles fuse with the presynaptic terminal,  undergoing exocytosis to release neurotransmitters into the synaptic cleft. But how exactly does the presynaptic terminal initiate this process? 

Vesicle exocytosis at the presynaptic terminal is inherently a stochastic process relying on the presence,  diffusion,  and chelation of calcium ions (Ca2+) which enter the presynaptic terminal upon depolarization by action potentials.

Accordingly,  this study uses graphic modelling in Python to examine the spatial and temporal interactions of Ca2+,  chelators,  and synaptic vesicles in the presynaptic terminal to determine the effects of Ca2+ binding to vesicle-associated Ca2+ binding targets on the release probability of synaptic vesicles. Based on geometric considerations,  a two-dimensional model of the presynaptic terminal is constructed,  employing the Monte Carlo Method to represent the probabilistic nature of Ca2+ conductance and vesicle fusion in the presynaptic terminal. For observable effect,  the model is animated and allows for the initial locations of Ca2+ and chelators to vary randomly while controlling the initial conditions of Ca2+,  chelator,  and vesicle concentrations. In doing so,  this model explores the relationship between Ca2+ influx into the presynaptic terminal and the number of vesicles that fuse with the presynaptic membrane. Consequently,  it allows the theoretical processes affecting vesicle fusion at a central synapse to be considered,  allowing further development in the understanding of chemical synapses and how their characteristics may alter electrical conduction.