Below is a list of thesis abstracts by fourth-year students in the Integrated Science Program:
THESIS PRESENTATIONS – MARCH 29, 2016
Laura Hogg: Postpartum Interactions in the GIT Microbiota
Supervisor: Dr. Jennifer Stearns
Abstract not available.
Julia Martinko: Effects of nicotine and the neonicotinoid insectide, imidacloprid, on hepatic lipid homeostasis
Supervisor: Dr. Alison Holloway
The prevalence of metabolic related diseases is greater than ever, after being on the rise for the past few decades. Exposure to environmental contaminants including pesticides has been suggested to cause metabolic perturbations leading to obesity and Type 2 Diabetes (T2D). Imidacloprid is a neonicotinoid insecticide which is thought to be active only at insect nicotinic acetylcholine receptors (nAChR). Imidacloprid is one of the highest usage pesticides (approximately 20% of the global pesticide market) and thus there is widespread human exposure. Imidacloprid has been shown to disrupt insulin-stimulated glucose uptake in hepatocytes and adipocytes and increase lipid accumulation in adipocytes; these are key mechanisms underlying insulin resistance, obesity and type 2 diabetes. Furthermore, there is evidence that imidacloprid exposure in vivo has profound effects on liver metabolism. Since the liver plays a key role in both glucose (gluconeogenesis) and lipid (lipogenesis) production, it plausible imidacloprid acts at the liver and impairs metabolic homeostasis via these pathways. Therefore the goal of this thesis was to investigate if imidacloprid exposure perturbs hepatic gluconeogenesis and/or lipogenesis. To investigate this question, McA-RH7777 rat hepatoma cells were treated with imidacloprid (0.1, 1.0 and 10 micromolar). Cells were also treated with equimolar concentrations of nicotine to facilitate comparisons with a known agonist of the mammalian nAChR. RNA was reverse transcribed and mRNA expression was compared using quantitative real-time polymerase chain reaction. Functional assessment of changes in lipogenesis (i.e., cellular lipid accumulation) was determined using Oil Red O staining.
In cells treated with imidacloprid, mRNA expression for several lipogenesis genes was significantly increased; imidacloprid-treatment affected more genes involved in lipogenesis than nicotine treatment suggesting a more profound effect on lipogenesis compared to nicotine. However, despite changes in gene expression of lipogenic genes, imidacloprid did not increase lipid accumulation in hepatocytes. Expression of genes involved in gluconeogenesis was also increased by imidacloprid; the effects of imidacloprid were similar to those seen with nicotine. The functional consequences (i.e., glucose production) of these changes in gene expression have yet to be determined. In summary, this study provides evidence to suggest that imidacloprid may perturb metabolic homeostasis by disrupting pathways involved in hepatic glucose and lipid production. These results suggest that the studies on the effects of imidacloprid exposure on the risk of developing metabolic diseases in human populations are warranted.
Drake Lee: Simulating the Gamma Field in the McMaster Nuclear Reactor using G4STORK
Supervisor: Dr. Adriaan Buijs
Abstract not available.
Kira Innes: The effects of cognitive response inhibition training on whole-body physical endurance performance
Supervisor: Dr. Steve Bray
Engaging in cognitive tasks that involve executive functions impairs performance on subsequent physically demanding tasks. Response inhibition is a core executive function involved in over-riding habitual or pre-potent responses on cognitive tests (e.g., Stroop test). It is also thought to be operative during strenuous physical exercise when people override their urge to quit as they near exhaustion. The purpose of this study is to examine the effects of cognitive response inhibition training on physical inhibition control. Participants perform a baseline graded exercise test to exhaustion (GXT) on a stationary bike and then are randomized to conditions that perform nine sessions either of cognitive response inhibition training or sham training (control training; in which the tasks mimic those in the inhibition training condition while omitting the aspect that requires inhibitory control) over a period of three weeks. Following training, participants perform a final GXT. It was hypothesized that following training, a greater positive increase in GXT performance would be seen in the active training group as compared to the control group. No difference in the change in GXT performance was found between the two conditions. This suggests that training through a series of cognitive response inhibition tasks may not lead to improvements on a physical inhibition control task and that training response inhibition control may be more complex than previously thought.
Leah Hayward: The effect of cold acclimation on thermal regulation in high- and low-altitude deer mice bred for 2 generations in the lab
Supervisor: Dr. Grant McClelland
Thermogenesis, or metabolic heat production, is an important homeostatic mechanism allowing mammals to effectively respond to changes in environmental temperature.
In high altitude environments, small mammals, such as the deer mouse (Peromyscus maniculatus), must sustain thermogenesis in reduced temperature despite persistent low oxygen availability. Since heat production is metabolically demanding, oxygen availability can impose limits on a mammal’s ability to maintain body temperature. High altitude mice likely circumvent this by increasing their capacity for heat production and/or reducing the ambient temperature at which they increase metabolism (defined as the lower critical temperature of the thermoneutral zone). The goal of this study is to determine the relative contributions of genetic variance and adult phenotypic plasticity to thermoregulation in P. maniculatus. I analyzed both the thermoneutral zone and maximal metabolic rate of F2-generation deer mice originally native to either highland or lowland environments. 20 mice were divided into two acclimation groups to assess phenotypic plasticity: 1) warm normoxic controls, and 2) cold normoxic kept at 5°C for six weeks. Measurements of the thermoneutral zone and maximal metabolic rate were performed using flow-through respirometry. I found that the low altitude mice responded to cold acclimation with a shift in the thermoneutral zone and an increase in thermogenic capacity relative to controls. It is expected that the highland-native population will experience similar changes, but the lower critical temperature of the thermoneutral zone will be decreased relative to their lowland counterparts. Determining the mechanistic basis for these thermoneutral zone shifts will provide novel insight into acclimation response and the effects of altitude on thermoregulation.
Daim Sarder: Subcellular localization of IL-33 within mouse lung epithelial cells stimulated with Oncostatin M
Supervisor: Dr. Carl Richards
Diseases of the lung such as pulmonary fibrosis, allergic rhinitis, asthma, and cancer present highly complex pathologies that are caused by many different factors. One of these factors includes the role of the immune system and the interaction between persistent inflammation and disease. IL-33 has been classified as a dual function cytokine which functions as both a potent inducer of the type 2 immune response, and a constitutively expressed protein in the nuclei of epithelial and endothelial cells to function as an “alarmin”. The purpose of this study is to examine the regulation of IL-33 by Oncostatin M, a secreted member of the gp130 cytokine family with significant roles in regulating inflammation, by assessing the subcellular localization of IL-33 using an in vitro model of mouse lung epithelial cells. The C10 Type 2 alveolar epithelial cell line was used for this study and cultured for 24 hours before being stimulated with a control treatment and mouse recombinant Oncostatin M for a further 24 hours. Whole cell extraction and subcellular fractionation of the cells were conducted to separate the cytoplasmic and nuclear components. Proteins in the extracts were analyzed by conducting a western blot to probe for IL-33 and other proteins of interest. The analysis showed an increased expression of IL-33 in the Oncostatin M stimulated samples from the whole cell extracts, and an increased expression in the nuclear fraction compared to the cytoplasmic. This result shows that Oncostatin M upregulates IL-33 expression in mouse lung epithelial cells, but does so selectively in the nucleus. Determining the biological relationship between these two cytokines is important because the increased expression of both Oncostatin M and IL-33 in various lung diseases shown both in vivo and in human studies, presents a potential target of interest for the treatment of these diseases.
Nikolas Goncharenko: Molecular Dynamic Simulations of Protein Kinase G Domain B cGMP-Binding Complex to Determine Binding Dynamics and Allostery
Supervisor: Dr. Giuseppe Melacini
PKG (Protein Kinase G) is a serine/threonine specific protein kinase that is activated by the secondary messenger cGMP (cyclic-Guanosine Monophosphate). The binding of cGMP to PKG regulates a wide number of intracellular signaling pathways associated with cell differentiation, platelet activation, vasodilation, regulation of smooth tone, and memory formation in a variety of eukaryotes. However, the mechanism of cGMP binding and allostery is not well understood and X-ray crystal structures are available only for fragments of the protein. To reveal the mechanism of cGMP binding and allostery, molecular dynamic simulations were performed using the NAMD software package on the Shared Hierarchical Academic Research Computing Network (SHARCNET). The known crystal structures of the C-terminal cyclic nucleotide binding domain (CNB-B) of human PKG 1β (PBD ID:3SHR and 4KU7), which serves as a central controlling unit. These structures were used as a basis for the simulations. To validate the results of the simulations, protein NMR (Nuclear Magnetic Resonance) data from a previous comparative NMR analysis was used as a reference. The simulation will be valid if there is no significant deviation between the MD simulation and the NMR data for the corresponding state. Based on the backbone N-H order parameter (S2) values for simulated and experimental PKG, there is enough similarity for the simulations to be valid for certain regions of the protein. Long term results of this research will reveal the full mechanism of PKG-cGMP binding and allostery and have implications in cardiovascular physiology and pathology.
THESIS PRESENTATIONS – MARCH 31, 2016
Nick Luymes: The relationship between resource density and reproductive success
Supervisor: Dr. Sigal Balshine
In order to determine the reproductive environments in which organisms thrive, we need to understand how reproductive success varies with different characteristics of resources (e.g. food, territories, mates). While the quality of resources and their effect on reproductive success has been well studied in the past, little research attention has been directed towards the relationship between resource density and reproductive success. Increases in resource density are expected to be associated with a trade-off between the benefits of closely-spaced resources and the potential costs of high rates of conspecific interaction. The impact of this trade-off was studied using the plainfin midshipman fish, Porichthys notatus. Males of this species excavate nests under rocks, which vary naturally in density throughout the breeding sites. Midshipman nests were sampled throughout their breeding season (April – July) and information was collected regarding the local nest density and the total number of embryos. While male reproductive success was not significantly influenced by nest density, the relationship between male dominance (size) and male reproductive success was found to be strongest at intermediate densities. This observation may reflect the hypothesized trade-off between a female’s cost of searching for high quality males at low densities and the cost of increased male-male competition at high densities. Research into the relationship between reproduction and resource density can help in our understanding of the environments that promote species survival, which can have important applications for conservation.
Jonathan Park: Useful Field of View and Peripheral Target Detection during Driving Simulation
Supervisor: Dr. Hong-Jin Sun
Driving is a complex multitasking performance that requires drivers to detect any changes in the scene while performing other driving related tasks simultaneously. Previous research suggest humans cannot process all information within the visual field and that the extent of spatial attention is very limited. Research in this area led to the development of UFOV (Useful Field of View) test that measured the area over which a person can process information without head or eye movement. The aim of this project is to investigate peripheral target detection ability in drivers’ UFOV while performing simulated driving task.
During the experiment, participants were instructed to detect circular flashes that appeared on either side of the road within the simulation. Targets were shown at either far or close location from participants’ viewpoint and differed in four horizontal eccentricity levels of visual angles. The experiment comprised of two phases; single task (detecting targets) phase and dual task (detecting targets and controlling the vehicle speed) phase. For each target detection, accuracy and reaction time were measured.
The results indicate higher accuracy and lower reaction time to detect targets that were presented close to participant’s viewpoint at lower eccentricity levels. The performance deteriorated when targets were shown on higher eccentricity levels but unlike our initial hypotheses, participants performed better on both accuracy and reaction time during dual task than single task phase. Those results provide key insights on how drivers perceive peripheral changes in the scene and allows us to assess drivers’ UFOV during simulated driving.
Derek Hamly: Themes in the rise of America as world superpower
Supervisor: Dr. George Breckenridge
American politics have provided the world with a tremendous degree of entertainment. Whether as a pioneer of a new world democracy or as the arena for the most overtly political system on the planet, the United States of America is a country upon which the eyes of the earth have focused since its inception. Arguably the most mesmerizing aspect of America’s political journey has been its transition from being a society of evangelical farmers in the eighteenth century to the dominant global superpower emerging in the latter half of the 20th century. This project has explored the themes that might explain this unprecedented transformation. These themes include America’s political tradeoff between noninterventionism and expansionism as well as America’s perceived role as being a city upon a hill. These concepts and others are explored through this project to explain the political evolution between 1823 and 1952, which encompasses the complete turnaround of American foreign policy ideology. The specific indicators of this change include: America’s foreign policies, political party platforms, quoted politicians and analysis of political events. In the end it appears as if the United States of America as a world superpower is the product of a unique political maturation process that no other nation on earth has mirrored.
Supervisor: Dr. Gurmit Singh
Abstract not available.
Aaron de Jesus: The Kiducate Project: Healthy Living For Children
Supervisor: Dr. Constantine Samaan
Over the past 20 years, there has been a substantial increase of Type 2 Diabetes (T2DM) incidence and prevalence, only projected to keep increasing with time. This has been linked to the global epidemic of obesity. The traditional methods of preventing this increase has been through the use of expository teaching, either verbally or through text, and are undoubtedly associated with educational language. However, current research and culture has otherwise shown that narrative style of teaching (and thus the method of narrative video animation) can provide significant learning results. This is seen in the literature, ranging from historical contexts to sociological studies. From this, one comes to see the benefits of communicating with a narrative plot line as opposed to the traditional expository rigidity. Although there are many methods of teaching children (ie. through books, pamphlets, and oral conversation), there does not seem to be an effective use of child-friendly communicative outlets. This project aims to bridge this gap between scientific research and a general audience directed for child comprehension by providing a series of animated videos on healthy living. The rarity of such productions makes this project worthwhile for pediatricians and parents, providing understandable information in a child-friendly form.
Supervisor: Dr. Ishac Nazi
Abstract not available.
Nathaniel Smith: Shrinking gold nano-sandwiches to make blood glucose tests
Supervisor: Dr. Leyla Soleymani
Nanotechnology promises to solve a significant roadblock in developing affordable blood sugar tests for diabetes. The current issues nanofabrication techniques face, involve the tradeoff between speed, reproducibility, and cost. Typically, top-down techniques are fast and accurate yet costly, while bottom-up techniques are simpler yet less reproducible. Immense research is going into self-assembled monolayers (SAMs), a bottom-up technique that demonstrated promising properties, like improved conductivity and surface enhanced Raman scattering (SERS). Biosensors with these properties will potentially be capable of single-molecule detection.
We pioneered a fabrication procedure for SAM biosensors out of gold nanoparticles (AuNPs) that aims to make improvements on speed, cost, sustainability, and reproducibility. This is the first procedure to ever combine two distinct surface modifications to AuNP monolayers: stacking and wrinkling. Given that stacking and wrinkling of AuNP monolayers have both demonstrated improved conductivity and SERS in separate experiments; we hypothesize that these properties will improve dramatically in devices with a high number of stacked monolayers and magnitude of surface wrinkles. A conventional method was chosen for the assembly of AuNP monolayers, where AuNPs were deposited on the surface of pre-stretched polystyrene. This allowed for the polystyrene substrates to shrink when heated over 130˚C, subsequently leading to the wrinkling of the gold surfaces, similar to crumpling tinfoil. In order to glue monolayers together, diaminooctane was chosen, since it contains two gold-loving nitrogen groups at its poles. The resulting devices matched our predictions, and may be used as prototypes for glucose biosensors.
Katie Maloney: Understanding the Scale and Spatial Arrangement of Landforms in Modern Glacial Environments
Supervisor: Dr. Carolyn Eyles
There are uncertainties that can arise from facies models because the 3-dimensional geometry of the sedimentary units is often inferred from 1-dimensional vertical profile data obtained from outcrops and boreholes. This can result in ambiguity in determining the spatial distribution of facies and their lateral continuity. To reduce uncertainty, the scale and spatial distribution of glacial landforms, (e.g. braid bars and moraines) were analyzed in a modern environment. The proglacial fields of three Icelandic outlet glaciers Skaftafellsjökull, Svínafellsjökull, and Morsárjökull were investigated by collecting sedimentological and geomorphological data through field work and remote sensing. The field data were integrated with LiDAR data and satellite imagery from Google Earth to establish trends in the spatial arrangement of the glacial environments and landforms. These trends appear to relate to the distinct geologic setting and behaviour of each outlet glacier. The general trends that are observed can be used to understand the controls that would have affected the deposition of Quaternary deposits, which are now found in vertical succession underlying previously glaciated terrains. Understanding the scale and spatial arrangement of modern glacial deposits will greatly enhance our ability to determine the geometry and interconnectedness of permeable units, most commonly fluvial and glaciofluvial deposits, which form important aquifers in previously glaciated areas such as Southern Ontario.
Amy Jenne: A Comparative Study on Five Different Soundless Chemical Demolition Agents
Supervisor: Dr. Carolyn Eyles
Soundless Chemical Demolition Agents (SCDAs) have been used both industrially and commercially with increasing popularity since their discovery in the 1970’s. Apex Equipment and Rentals has recently created their own version of this product. SCDAs are a type of green method to help with the demolition of rocks and/or concrete. A slurry is created from mixing the product with water, and poured into drilled holes in the structure. There is a volume change caused from the reaction with water, which exerts pressure into the substance, eventually surpassing the tensile strength of the material, thus causing a break. The purpose of this project was to examine five different SCDAs next to one another to determine which was the most effective. There are three main properties that need to be examined for this purpose: 1) The product that is first to crack, 2) The product that reached crack widths of 25.4 mm first, and 3) The product that creates the largest cracks in the substance after the reaction. Five concrete blocks of dimensions 23 1/8th X 231/8th X 231/8th inches were used as the test material for the SCDA. A 1.5 inch diameter hole was drilled into the center and the slurry was placed into each hole. The blocks were monitored for 48 hours until the completion of the expansion, which occurred for all products tested. The expected outcome of the results is that the products created by the company will be the most effective in each of the three categories listed above. Overall, this project will serve to provide information to customers of this company about their products.
Lauren Oldfield: Analysis of the spatial and temporal hydrogeological impacts of road salt contamination in the York and Halton Regions of Southern Ontario
Supervisor: Dr. Carolyn Eyles
Commercial usage of road salt to de-ice roadways began in the 1940’s in Canada and presently, the total quantity applied has increased to reach an estimated 5 billion tonnes annually; of which, approximately 50-55% enters the subsurface through soil and groundwater. This study focuses on the York and Halton Regions of Southern Ontario, both of which rely on groundwater for potable water. Each region has municipal pumping stations and available monitoring data of the groundwater geochemistry, which can be used to analyze potential contamination related to road salt (ie. chloride, sodium, conductivity, etc). The data ranges from 1985-2015 CE for Georgetown and 1991-2015 CE for Halton. However, as data coverage varies each year due to geochemical sample variance, the years with the most coverage in both areas (2010-2015) are the principle years analyzed spatially. Trends in contaminant concentrations were analyzed through linear regression modeling. ArcGIS was used to determine correlation and covariance between contaminant concentrations and geological factors, such as bedrock elevation, proximity to roads and water bodies, subsurface complexity/type, etc., was performed through band collection statistics. As a result of the aforementioned tests, it has become evident that salt concentrations in these areas have increased more than 100%, on average, since 1990. Many of the wells tested in both areas have an upward linear trend of contaminant concentration with time. Contamination is greater, and more susceptible to large influxes, in urbanized areas with higher road concentration. The findings from this study will aid municipalities in identifying the mechanisms by which salt moves in the environment, discovering areas particularly at risk due to road salt contamination, and potentially contribute to the development of remediation plans.
Supervisor: Dr. Johnathon Stone
Abstract not available.
Rui Xu: The Elastic properties of Bilayer and Monolayer Membranes
Supervisor: Dr. An-Chang Shi
The elastic properties of self-assembling bilayer and monolayer membranes are studied using the self-consistent field theory, using a model system of amphiphilic AB diblock copolymers and ABA triblock copolymers dissolved in hydrophilic homopolymers. We calculate the free energy of the membranes in planar, cylindrical, and spherical geometries in order to extract bending modulus, Gaussian modulus, and line tension. We find that the bending modulus of the triblock monolayer membrane is greater than that of the diblock bilayer membrane. We find that the Gaussian modulus and line tension of the monolayer membrane suggest it is stabilized against pore formation for a greater range of copolymer architectures, and with higher pore formation energy penalties than the bilayer membrane. We evaluate equilibrium bridging and looping fractions for triblock copolymers in the monolayer membrane and discuss the implications for dynamically induced membrane curvature. We discuss the elastic parameters of the membranes in terms of their biological equivalents, the phospholipid bilayer membrane and the bolalipid monolayer membrane. The bolalipid membrane is exclusively found in Archaea, and we suggest it has mechanical properties that allow Archaea to survive in harsh environments.
Supervisor: Dr. Gianni Parise
Abstract not available.
Robert Rawlins: Examining food waste on the McMaster University campus
Supervisor: Dr. Altaf Arain
In Wasted: How America is wasting up to 40% of its food, Dr. Dana Gunders discusses the reality that America throws out almost half of the food it produces, costing the country over $165 billion. The extremity of these claims evoked questions regarding the article’s accuracy, the scope of the issue, steps being taken or potential options to reduce food waste, and more specifically, the state of food waste at McMaster University.
In order to answer these questions, three main methods were utilized. Firstly, a two-part literature review was conducted with the goal of first gathering data on global, national, and local food waste, its sources and driving forces, and secondly, information on initiatives that are in place and working now and expert-suggestions on initiatives that should be implemented. With a well-established understanding of the state of food waste, attention was turned towards McMaster University for the second phase during which interviews were conducted with employees of McMaster’s hospitality services department. Interviews were conducted with one individual in an administrative role, while the other filled a managing chef role. The interviews were focused on gleaning information on food waste initiatives, sustainable practices, employee opinion and understanding on food waste, and strategy to reducing food waste at McMaster. Finally, data was collected from La Piazza, Pizza Pizza, and Tim Hortons in the McMaster University Student Centre (MUSC) in order to confirm or challenge the statements made by the interviewees.
In the end, it is clear that Gunders did not exaggerate, but in fact accurately described the situation of food waste around the world. Approximately a third of total food produced globally is thrown out. This has huge economic impacts: Over US$900 billion wasted every year; Severe environmental consequences: Food waste accounts for roughly 10% of global GHG emissions; and terrible social implications: while only $US 3.2 billion would negate the hunger of 66 million sub-Saharan African children, the US alone wastes US$165 billion every year. Evidence from a McMaster waste audit and interviews with McMaster employees supplemented with data collection reveals that while food waste is the largest contributor to solid waste at McMaster, a tight financial budget means a low production of food waste relative to the degree of global food waste. What this study did not take into account is the waste produced by consumers, which is the largest source of food waste in every scenario. As a student of McMaster, one has to walk away from this research increasingly concerned about the lack of attention being given to the issue, the lack of knowledge regarding food waste in North America, and therefore the lack of opportunity for behavioural changes to take place here. Although further research is always beneficial, this report clearly demonstrates the necessity for the implementation of food waste initiatives that continue to bring more awareness to the issue and inspire them to change the way they think about food. This report is intended to do something of the sort.
THESIS PRESENTATIONS – APRIL 5, 2016
Mankeeran Dhanoa: Validation of an in vitro Model of Endothelial Dysfunction using human Endothelial Cells derived from Induced Pluripotent Stem Cells (iPSCs)
Supervisor: Dr. Eva Szabo
Endothelial dysfunction is a pathological state of impairment of endothelial cells that constitutes a critical step in the progression of atherosclerosis, a condition characterized by plaque development within the coronary and larger arteries of the body. The development of endothelial dysfunction stems from a complex interaction between lipid metabolism and the immune system, and is implicated in the development of cardiovascular diseases such as coronary artery disease (CAD). Whereas CAD is typically associated with lifestyle and metabolic risk factors such as smoking, diabetes, and obesity, early onset CAD (EOCAD) is a form of CAD that often targets a younger demographic that may not necessarily possess typical risk factors. Therefore, it is likely that EOCAD has a genetic basis that targets endothelial cell function. Given the inaccessibility of obtaining endothelial cells from live subjects, an investigation of this nature can be facilitated through an in vitro model of endothelial dysfunction using endothelial cells derived from induced pluripotent stem cells (iPSCs). Using molecular techniques, a validation of this model can be facilitated in order to assess whether endothelial cells derived from iPSCs in vitro possess functional properties of endothelial cells in vivo. The applications of these findings can prompt further investigations into genetic mutations underlying EOCAD, while contributing to the limited body of knowledge surrounding the mechanisms of endothelial dysfunction in order to improve clinical outcomes.
Supervisor: Dr. Carmel Mothersill
Abstract not available.
Nicole Yokubynas: Use of Nutrient Limitation as a Probe for Unlocking Natural Product Drug Discovery from Actinomycetes
Supervisor: Dr. Eric Brown
The overwhelming increase in antibiotic resistant pathogens concomitant with insufficient discovery of novel antimicrobial agents poses a serious threat to modern medicine. The majority of successful antibiotics are derived naturally from Actinomycetes bacteria grown on nutrient-rich media; yet, most of these compounds target a limited range of functions unique to bacterial cells. Recently, synthetic compound screening against Escherichia coli (E. coli) under nutrient restriction yielded new antibacterial targets of metabolite biosynthetic pathways. This study investigates the use of nutrient restriction in natural product drug discovery to further isolate novel compounds targeting nutrient metabolism.
A collection of 80 Actinomycetes bacteria grown in both supplemented and minimal nutrient solid growth media were tested for growth inhibition against E. coli MG1655 under nutrient restriction using an agar diffusion assay. This screen produced active antimetabolites unique to Actinomycetes growth on both supplemented and limited media conditions, thus supporting the existence of antimetabolites that would be undetected using traditional screening protocols. However, a subset of the active antimetabolite derived in nutrient-rich conditions demonstrated up to 300% increased growth of E. coli following extraction. We discovered nutrient-carryover during natural product compound extraction to be responsible for masking a significant portion of antimetabolite activity. An additional 10 non-antibacterial producing Actinomycetes strains were grown in both supplemented and minimal growth conditions and were systematically screened against 30 minimal essential auxotrophic E. coli strains. Growth rescue was observed to be both strain and nutrient specific. Of particular concern, pantothenate and thiamine auxotrophs consistently demonstrated 100% growth rescue, suggesting that traditional extraction methods would fail to identify novel inhibitors of these nutrient biosynthetic pathways. Given the severity of antimicrobial resistance, this research demonstrates a significant step forward in determining how novel antimetabolites will be discovered, extracted and purified in the future. Ongoing research will be dedicated to determining the alternative methods required to isolate these antibiotic compounds targeting nutrient metabolism.
Kali Iyer: Target validation of the biosynthetic enzyme BioA, through mouse infection models
Supervisor: Dr. Eric Brown
Since the emergence of antibiotics, the unwavering ability of bacteria to adapt to antimicrobial treatments has terrified observers. To combat resistance, a small number of “new” antibiotics have been developed. Unfortunately, these new antibiotics rely on minor chemical modifications to a limited number of previous scaffolds. These modifications predispose these “new” drugs to established resistance mechanisms. Critical nutrients are often unavailable to bacteria during infection, forcing the use of biosynthetic pathways. Therefore, inhibition of these metabolic pathways represents an untapped group of targets for new antibiotics. Of particular interest is the biotin biosynthetic pathway as it is not present in higher organisms and enzymes in the pathway, specifically BioA, have been shown to be vulnerable to inhibition. Mouse models were used to test the essentiality of BioA and biotin production during bacterial colonization. Using a knockout of the BioA gene in Salmonella Typhimurium, mice are infected with equal amounts of the knockout and wild type Salmonella. Once the infection has run its course the quantity of each type of bacteria was. If the knockout Salmonella is present at lower numbers than the wild type has a reduced capacity to colonize when biotin is not being produced. Additionally, a BioA knockout was produced in Klebsiella pneumoniae to be tested in mice for further understanding of a BioA inhibitors antibiotic spectrum. Together this knowledge will provide further support for the pursuit of BioA as an antibiotic target and guide future drug development.
Vincent So: The Role of Diacylglycerol Kinase Epsilon in Modulating the p53 Tumor Suppressor Protein
Supervisor: Dr. Richard Epand
Diacylglycerol kinases (DGK) are a family of enzymes involved in the catalysis of diacylglycerol (DAG) into phosphatidic acid (PA). Both DAG and PA play an important biological role as components of molecular membranes, and as precursors for lipid-signaling molecules, triglycerides, and phospholipids. Among the ten mammalian isoforms of DGK, only one isoform, DGKε, exhibits substrate specificity for DAG species. DGKε has been linked to countless disease processes such as epilepsy, Huntington Disease, Atypical Hemolytic Uremic Syndrome, and cardiac hypertrophy.
Recent studies show that knocking out DGKε leads to an overall increase in glycerol incorporation, which suggests that DGKε plays a role in regulating lipogenesis. Furthermore, the p53 tumor suppressor protein, which is mutated in a large proportion of cancers, has also been shown to regulate lipid metabolism, and exhibits strong electrostatic interactions with lipids such as phosphatidic acid, in vitro (PA). This study aims to evaluate the interplay between DGKε, the p53 tumor suppressor protein, and a key regulator of glycerol incorporation (glycerol kinase). In this project, DGKε wild-type (DGKε-WT) and DGKε knockout cells (DGKε-KO) were cultured and used in western blots to compare the relative levels of p53 and glycerol kinase (GK) in both cell types. DGKε-FLAG plasmids were also generated and used to transfect DGKε-KO, in an attempt to reverse any DGKε-dependent effects on lipid metabolism. If DGKε does play a role in regulating p53 expression, DGKε might serve as a promising target for cancer therapy.
Supervisor: Dr. Sue Becker
This thesis compared the novel intervention of progressive thresholding target neurofeedback (NF) levels in enhancing EEG-Frontal Alpha Asymmetry (AA) levels relative to standard NF control interventions. Ten university students were randomized to these two groups and participated in eighteen thirty-minute session interventions across six weeks. Participants’ abilities to bring their EEG-Alpha power closer to symmetry from a lack of left hemispheric activity were analyzed as a marker of reducing predisposition to depression and negative mood. Participants randomized to the progressive thresholding group are expected to achieve more symmetrical AA levels in a timelier manner than their standard NFB counterparts. Enhancements are expected to be observed in both neurofeedback intervention groups. Enhancements caused by interventions would be observed both through EEG and behavioral measures of stress and anxiety, including the Perceived Stress Scale (PSS), Beck Depression Inventory (BDI), and Beck Anxiety Inventory (BAI). Improvements in behavior are anticipated to correlate with decreased alpha asymmetry at electrodes FP1 and FP2. This and subsequent studies will elucidate benefits of NF studies on depression and lay the groundwork for new techniques in conjunction including machine learning for personalized interventions.
Trystan Nault: Lifestyle Factors and Associated Cognitive Function
Supervisor: Dr. Sue Becker
Previous research has indicated that lifestyle factors such as binge drinking alcohol, depression, stress, and anxiety influence performance on cognitive tasks that are dependent on the activation of the hippocampus. This data is also consistent with rodent data indicating that these factors also impact hippocampal neurogenesis. This consistency suggests a role for neurogenesis in some generalized and hippocampal-dependent tasks, particularly those with a high interference component. Given the prevalence of binge drinking culture and the high levels of stress and depression experienced by university students found on university campuses globally, these issues are of particular interest these aspects are of particular interest for this project. Through further investigation and increased awareness, it is hoped that the current study may contribute to an appropriate cultural shift amongst young people on these university campuses and beyond. The current study will investigate potential the relationships between adolescent binge drinking, cannabis consumption, depression, anxiety, and stress levels and performance on hippocampal dependent and more generalized cognitive tasks. While direct measurements of hippocampal neurogenesis will not be taken Performance on these tasks will be a good indicator of overall hippocampal functionality and in some instances potentially provide indirect insight on the rate of neurogenesis. It is expected that subjects who exhibit binge drinking behaviours, consume cannabis in excess, and those that are depressed, anxious or stressed will show cognitive deficits in comparison to healthier individuals. The findings of this study may eventually be useful as part of a larger body of evidence advocating for mental health awareness, stress reduction and mindfulness and against adolescent binge drinking and other drug recreational use.
Jessica Kun: The use of photodynamic therapy in the detection and treatment of Barrett’s esophagus
Supervisor: Dr. Qiyin Fang
Barrett’s esophagus is a precancerous disease with the potential to become esophageal adenocarcinoma, a malignant cancer with a five year survival rate of 12%. Early detection and treatment of Barrett’s Esophagus is crucial to the survival of the patient; however, current detection techniques can be erroneous and take time to process. A more favourable method of treatment is a real time seek-and-treat strategy at the cellular level through the use of photodynamic therapy. 5-Aminolevulenic acid has previously been tested as a contrast agent to highlight features at a single cell level. In addition to this, machine learning can be used to extract these highlighted morphological and textural features of the cells to more accurately target specific cells. This procedure has the potential to alleviate cost and discomfort to the patient in comparison to the current biopsy and histology treatment as there is no need to remove samples from the patient. The objective of this project is to enhance the detection of Barrett’s esophagus. In order to do this, we use fluorescence imaging of an in vitro model of Barrett’s esophagus and support vector machines to properly detect and classify the cells to ensure specific cells are being targeted for treatment. We iteratively test the support vector machine classification software to ensure sensitive and specific identification. Photodynamic therapy with the help of machine learning is a promising route for cancer prevention.
Supervisor: Dr. Jonathan Dushoff
Abstract not available.
Heather Fice: The effect of MMP2 on Extracellular Matrix Remodelling and Heart Development in Larval Drosophila melanogaster
Supervisor: Dr. Roger Jacobs
The Drosophila melanogaster dorsal vessel is the contractile vessel and analogue of the vertebrate heart, performing the task of pumping hemolymph through the body. Through development, as the dorsal vessel increases in size there is no change in cell number, meaning that processes such as cell growth extracellular matrix (ECM) remodelling are of critical importance. Studying the contributing processes of remodelling in dorsal vessel development could provide insight into many cardiovascular defects present in human disease. In understanding ECM remodelling in D. melanogaster, one should examine the enzymes that regulate ECM degradation, matrix metalloproteinases 1 and 2(MMP1, MMP2). It is hypothesized that the expression of mmp2 in the hemocytes, is a major contribution to ECM remodelling. Through the transgenic UAS-GAL4 gene expression system, the longevity and dorsal vessel phenotype have been examined. Genetic crosses were used to alter the expression of MMP2 in the hemocytes employing a Peroxidasin (Pxn) GAL4 driver in three ways; a down-regulation of MMP2 through RNAi, overexpression, and a decreased expression in MMP2 through the overexpression of their endogenous inhibitor, the Tissue Inhibitor of Metalloproteinases (TIMP). In studying longevity UAS mmp2 RNAi flies were crossed with the PxnGal4 driver at varying temperatures to control expressivity. To study the phenotype, UAS mmp2 RNAi, UAS mmp2, and UAS TIMP were crossed with PxnGal4. Once at third larval instar, they were dissected, labeled with actin and integrin markers, and subsequently imaged with a Leica sp5 confocal microscope. Through these experiments, the necessity of MMP2 in heart remodelling may be demonstrated through reduced longevity and altered heart phenotype. Understanding dorsal vessel malformations in D. melanogaster, elucidates potential sources for heart malformations in mammalian species, including humans.
THESIS PRESENTATIONS – APRIL 7, 2016
Braedan Huras: Influence of Wild Type Genetic Background on Epistatic Interactions
Supervisor: Dr. Ian Dworkin
Organisms of the same species have different wild type genetic backgrounds if they possess natural genetic variation, even if the phenotypes appear to be the same. These backgrounds can influence mutations and other genetic conditions differently. Therefore, considering the background-dependence of mutant expressivity is essential for both academic and clinical studies. Since background-dependence affects many mutant alleles, it may also affect the products of their interactions. Epistasis, which occurs when alleles at different loci interact and produce a modified phenotype of one of the alleles, may also be affected by genetic background. Drosophila melanogaster is the model organism for this study, and the genes tested were scalloped and vestigial because their mechanisms in determining wing shape and size are well-known. Also, plenty of information on their background-dependence is available. This study hopes to further the understanding of how background-dependence affects epistasis and how it might influence interactions between alleles of different severity. In order to achieve this, individuals possessing alleles of these genes were crossed, and the background effects were tested by examining the difference in wing phenotype between individuals of each background. It is expected that individuals possessing alleles that individually show the greatest background-dependence will also exhibit the greatest background-dependence when they interact with each other. Information gained from this study will further the understanding of genetic background effects and epistasis, as well as emphasize the need to consider and account for it when performing studies such as those on genetic medical conditions.
Mike Gill: Objectives-based analysis of the Spark Peer Mentorship program
Supervisor: Dr. Chad Harvey, Dr. Lori Goff
Students transitioning into university often face heightened levels of academic stress, difficulties with social integration, and a decrease in their personal health and wellness. Mentorship has been shown to be an effective intervention for these three common experiences in young adults. However, studies have shown inconsistent results across formal mentorship programs. This mixed methods study assesses the extent to which the objectives of MSU Spark, a formal, term-long peer-mentorship program for first year students at McMaster, are being met.
Surveys were circulated to both the Fall and the Winter cohort of Spark students at the beginning as well as at the end of the program. The first survey for each cohort stood as a control for participation in Spark, and the first Winter survey provided a baseline for students who had completed first term, but not the Spark program. Quantitative responses were grouped by program objective and evaluated through elasticnet regression and ANOVA. Qualitative responses were analyzed via thematic analysis.
Quantitative results suggest that in two objectives, Spark successfully created significant desirable change in participants: comfort and social support, as well as usage of campus services. First generation students also demonstrated significant benefit in two more objectives: goal setting and direction as well as appreciation and practice of reflection. Qualitative results revealed deep relationships were formed between students and mentors, but less so between students and their peers. Resulting recommendations for program improvement have the potential to positively impact the transition experience for hundreds of students at McMaster each year.
Aakash Shaw: Patient’s perspective of the Hospital Elder Life Program (HELP)
Supervisor: Dr. Chad Harvey
Delirium is the acute and fluctuating onset of confusion with a decline in cognition, attention, or level of consciousness. Delirium can have serious physical and financial consequences for patients and is a great liability for hospital care. Hospitalized elder patients are often at greater risk of delirium development due to increased patient populations and increased patient turnover rates. These recent changes have been linked with certain risk factors including improper sleep and nutrition, social isolation, and decreased mobility. The Juravinski Hospital is one of the few hospitals in Ontario to actively run a preventative program. The Hospital Elder Life Program (HELP) uses five interventions: Orientation, Therapeutic Activities, Range of Motion, Meal Assistance, and Sleep Promotion. This model is based off a study conducted by a group at Yale University in 1999 (Inouye et al., 1999) that identified these risk factors and proposed the HELP model. As our model is based off an old study from a different population, this study aims to identify Juravinski patients’ perspectives on HELP interventions, and possible changes that could be made to better serve this population. We are conducting interviews and questionnaires to identify our patients’ perspectives. We expect to identify a continuum of preferred and less preferred activities, as well as suggestions for new services. The goal of this study us to implement suggestions by continuing preferred activities and changes which will strengthen less preferred, but potentially important (e.g. range of motion) interventions while helping patients feel more comfortable to participate.
Supervisor: Dr. Shucui Jiang
Abstract not available.
Supervisor: Dr. Julia Abelson
Abstract not available.
Alexandra Garbe: The Objective Evaluation of Hypsarrhythmia in the Diagnosis of Infantile Spasms
Supervisor: Dr. Kevin Jones
Infantile spasms is a rare seizure disorder that occurs during infancy, which can have catastrophic effects, in addition to dangerous side effects from medication. This syndrome is characterized clinically by epileptic spasms, which range from very intense to barely visible movements. These spasms are usually accompanied by developmental delay and a characteristic interictal electroencephalography (EEG) pattern, known as hypsarrhythmia or modified hypsarrhythmia. The accurate identification of hypsarrhythmia or modified hypsarrhythmia is essential to determine the diagnosis of infantile spasms, response to treatments, and potential relapse, but these patterns are often difficult to identify. The goal of this study is to design and test a set of objective criteria that will improve the accurate evaluation of hypsarrhythmia and modified hypsarrhythmia by physicians reviewing these EEGs. A literature review was conducted to assess the current research and compile the objective criteria. Patient files were reviewed to collect epidemiological data, and to analyze the progression of the disorder, EEG reports, and course of treatment. The EEGs used to determine diagnosis, treatment changes, and relapse were re-analyzed by a board certified electroencephalographer using the objective criteria. These results were compared to the original reports, using Fisher’s exact test, to assess the impact of the objective criteria on the evaluation of hypsarrhythmia/modified hypsarrhythmia. Although there was not a significant difference, the results still suggest that the objective criteria can have a clinical impact. Specifically, patients who experienced resolution of spasms, but not resolution of hypsarrhythmia on the original EEG report, likely would have received a different diagnosis or treatment decision if the new report using the objective criteria indicated resolution of hypsarrhythmia.
Lauren Smith: Measuring the Effective Temperature of M. magneticum
Supervisor: Dr. Cécile Fradin
Magnetospirillum magneticum is a magnetotactic bacterial (MTB) species containing ferromagnetic structures that allow it to align with the earth’s magnetic field. This alignment process, known as magnetotaxis, was originally thought to be similar to the movement of a magnetic dipole in a field, however; studies have suggested that biological noise from the cells make this process more difficult to understand. There is disagreement between studies on MTB surrounding the amount of non-thermal noise present from the movement of cells during magnetotaxis. This is quantified as the effective temperature and is calculated from the magnetic moment and orientation of the cells. The main focus of this project was to determine whether the orientation and therefore effective temperature of the cells during magnetotaxis is dependent on magnetic field strength.
This project took a two-pronged approach to compare data from experiments focusing on single-cell tracking and an ensemble of cells. The single-cell tracking experiments included recording videos of the cells in a field and using video tracking software to analyze their alignment in varying external magnetic fields. The ensemble data came from an optical experiment that attempted to use the birefringent properties of a solution of cells in a magnetic field to calculate their alignment based on the polarization of light passing through the sample. These approaches were motivated by the variety of methods used in previous studies on the topic, and the possibility that additional information may arise by comparing results from these two perspectives.
Jenin El-Sayes: Effects of aerobic exercise on corticospinal excitability in active and sedentary humans
Supervisor: Dr. Aimee Nelson
Aerobic exercise is known to have many positive effects on brain health such as increasing levels of growth factors and increasing angiogenesis. Aerobic exercise primes the brain for neuroplasticity and a single bout of exercise can increase cortical excitability. This study aimed at deciphering changes in the cortex after aerobic exercise. In this study, we investigated the effects of aerobic exercise on motor evoked potential in active and sedentary/low physically active individuals. Before and after the exercise, motor evoked potential (MEP) recruitment curves were collected to determine levels of corticospinal excitability. The exercise consisted of cycling on a recumbent cycle ergometer for 20 minutes at of 50-70% of the age-predicted maximal heart rate (220-age). It was expected that the exercise would increase levels of corticospinal excitability, seen as increases in MEP recruitment curve slopes. Based on preliminary data, this hypothesis holds true for active individuals. However, in sedentary individuals, the opposite is seen: MEP recruitment curve slops decrease showing a decrease in corticospinal excitability. Therefore, only in certain cases can aerobic exercise make the brain more susceptible to neuroplastic changes. This information can be taken into account and utilized to enhance neuroplasticity protocols used in clinical populations, such as stroke, to further enhance and promote long-lasting neural changes and motor recovery.
Supervisor: Dr. Henry Schwarcz
Abstract not available.
Aaron Goldberg: Investigating Hawking radiation as a quantum catastrophe using analogue black holes
Supervisor: Dr. Duncan O’Dell
General relativity predicts that nothing, not even light, can escape from a black hole. This was dramatically challenged by Hawking in the 1970s. Hawking showed that, if you zoom in to the quantum scale just outside of a black hole, you see a ‘glow’ of particles emerging. Even though the predicted glow is much too faint to be seen in astrophysical black holes, scientists have been able to create analogue black hole systems in the laboratory, and have successfully observed analogue Hawking radiation.
However, the theory of Hawking radiation is incomplete; it predicts that particles emerging from black holes have phase singularities, i.e., ‘infinite’ frequencies. We attempt to understand these singularities using the mathematics of catastrophe theory, which was developed to characterize the singularities that can occur in any function with a given number of free parameters. We look for these characteristic signatures in analogue black hole systems ranging from water waves propagating on a counter-current to rotating Bose-Einstein condensates. The signatures will signify where the Hawking theory breaks down, and where new physics is needed to remove the singularities.
We have ruled out a number of potential connections between catastrophe theory and Hawking radiation, but the remaining candidates are still promising. In my talk, I will present the results of our various attempts. We hope that these lay the groundwork for attaining a more complete understanding of the quantum-mechanical nature of black holes.
Caroline van Every: Obesity genes and weight gain in response to rosiglitazone treatment in type 2 diabetes patients
Supervisor: Dr. David Meyre
Rosiglitazone belongs to the thiazolidinedione class of drugs, which are a group of glucose-lowering oral medications used in the treatment of type 2 diabetes. These drugs improve glycemic control in patients by increasing insulin sensitivity in hepatic, peripheral, and adipose tissues, as well as by increasing insulin secretion. However, a well-known and unwanted side effect of rosiglitazone treatment is weight gain. The expansion of adipose tissue triggered by rosiglitazone treatment can be related to processes implicated in the development of obesity. Currently, over 100 common gene variants in the human genome have been associated with obesity. These loci have also been shown to interact with individual behaviours, biological traits, medical conditions, and medical treatments when influencing body mass. However, no study so far has investigated the effect of genetic variants on weight gain in response to rosiglitazone treatment. The primary objective of this study was to investigate the effects of 23 obesity predisposing loci on patient weight gain in response to rosiglitazone during a 3-year median follow-up in the Diabetes Reduction and Assessment with Ramipril and Rosiglitazone Medications (DREAM) randomized clinical trial. Secondary objectives included the study of the 23 obesity predisposing loci on fasting and 2-hour glucose levels, as well as on incident type 2 diabetes in response to rosiglitazone treatment. Determining the presence of drug-gene interactions in the context of rosiglitazone treatment will have important applications in personalized medicine for diabetes patients.
Jonathan Ho: The development of a defined synthetic media for S. intermedius provides novel insights on the metabolic requirements of the Streptococcus milleri Group
Supervisor: Dr. Mike Surette
The Streptococcus milleri group (SMG) is a group of opportunistic pathogens that are part of the normal human gastrointestinal and respiratory microbiota. The SMG has been shown to be the causative agent of solid liver and brain abscesses, and has also been implicated in the pulmonary exacerbation of Cystic Fibrosis patients.
The SMG are innately resistant to sulfonamides because they lack the target enzyme dihydropteroate synthase (DHPS), an enzyme in the folate synthesis pathway. As folate is an essential molecule that is implicated in DNA and RNA synthesis, the absence of this enzyme suggests that the SMG use an alternative and currently unknown pathway to synthesize folate.
In order to identify the unique genetic and metabolic components of the SMG that allows this group of bacteria to proliferate without DHPS, we sought to create a defined minimal media in which the SMG can grow, providing us with a better understanding of the SMG’s metabolism, and specific molecules necessary for survival. A clone library of the Streptococcus intermedius B196 genome was also developed in order to identify the loci of the genes relevant to folate synthesis.
The investigation of sulfonamide resistance in the SMG is of prime importance to the current antibiotic resistance crisis. Few treatment modalities remain for resistant bacteria, and as the SMG have a high incidence of horizontal gene transfer with other streptococci, sulfonamide-resistant folate synthesis may soon become prevalent.
Julia Higgins: The effect of mathematical modeling software selection on accuracy of geological models
Supervisor: Dr. Carolyn Eyles
It is very important for geologists to be able to take singular points of data and interpolate them to represent a space or surface. Models like these are widely used in the field of geology with applications ranging from resource exploration to groundwater protection. Depending on the selection of modeling software, however, the results of maps and surfaces might vary due to how the program interprets different interpolation algorithms. This study took two open-source geographic modeling programs and compared their interpolation outputs from singular boreholes data collected around the Niagara area. The two freely available programs, R and QGIS, were used to run two different interpolation algorithms, inverse distance weighting and ordinary kriging. The results of the comparisons showed that there was a mathematical difference between the outputs of the same algorithm being run in different programs. This research is significant to geologists due to the inconsistency, inaccuracy, and error involved in what program is chosen for creating the models.
Li Ming Chen
Supervisor: Dr. Randy Dumont
Abstract not available.