MSc Student, Aristizabal Lab Characterizing the effects of human cancer-associated histone H2AZ mutations using S. cerevisiae Nucleosomes, the building blocks of chromatin, are composed of 146 base pairs of DNA wrapped around an octamer of histone proteins (typically two copies of H2A, H2B, H3, and H4). Chromatin, the packing structure by which DNA is condensed into chromosomes, is dynamic and can be altered in several ways, including: (1) the sliding, eviction, and deposition of nucleosomes, (2) the addition of posttranslational modifications (PTMs) to histone proteins and (3) the incorporation of histone variants in place of canonical counterparts. A wide range of mutations on histone-encoding genes have been identified among publicly available whole-exome sequencing data from human cancer patients. Some of these mutations have been demonstrated to disrupt the histone octamer, alter higher order chromatin structure, and affect histone tail dynamics, DNA accessibility and transcription factor binding. Although most of these mutations remain to be studied, some, termed “oncohistones,” have been shown to drive cancer development and are correlated with poor disease prognosis. My project seeks to advance our understanding of the effect(s) of these cancer-associated missense mutations to the histone H2A variant, H2A.Z, using budding yeast (Saccharomyces cerevisiae) as a model system. H2A.Z is implicated in a wide range of molecular processes, including transcriptional regulation, DNA replication, cell cycle progression, and DNA damage repair. It is also highly conserved from yeast to humans. Focusing on cancer-associated mutations that map to identical residues between yeast and humans, we have generated a library of 21 mutations which will be screened for effects on cellular growth, chromatin dynamics, and gene expression. This work will improve our understanding of the various mechanisms by which cancer-associated mutations affect genome function, providing some clues as to how they may contribute to cancer development and progression.
MSc Student, Snedden Lab Arabidopsis CML13 and CML14 Interact with Myosins and Function as Plant-Specific Myosin Light Chains Calcium ions (Ca2+) are widely present as secondary messengers in eukaryotes. Ca2+-signals are interpreted by Ca2+-binding proteins called sensors, which then regulate various responses. Apart from the highly conserved calmodulin (CaM), plants possess a distinct family of CaM-like proteins (CMLs) that function as Ca2+-sensors. CMLs primarily consist of Ca2+-binding EF-hands and lack any other functional domains. They are believed to act as sensor-relays by undergoing conformational changes induced by Ca2+ and interacting with target proteins. Among the 50 CMLs found in Arabidopsis, AtCML13/14 are particularly intriguing due to their unique biochemical properties and high expression levels in vivo. To investigate the function of CML13/14, we screened a yeast two-hybrid library to identify potential interacting proteins. Our screen led to the discovery of three unrelated families of putative targets: IQ67 domain proteins (IQDs; microtubule scaffolds), CAMTAs (transcription factors), and myosins (motor proteins). These proteins possess a structural characteristic known as tandem IQ-motifs, which are a special type of CaM-binding domain. Through in vitro and in vivo protein-interaction assays, we found evidence suggesting that CML13, CML14, and CaM are the primary interactors of these targets via their IQ domains within the CML family. Focusing on myosins as representative targets of CML13/14, we utilized confocal microscopy, in vitro kinetic assays, and in vitro binding tests to demonstrate that these CMLs act as novel myosin light chains. To gain further insights into their functions in vivo, we employed an inducible RNAi system to specifically silence either CML13 or CML14 in Arabidopsis. The resulting phenotypes were pleiotropic, indicating that these CMLs play crucial roles in development by regulating cytoskeletal function through their interactions with myosins and IQDs. In summary, our data suggests that CML13/14 are important regulators in various biological processes. They modulate cytoskeletal activity via their association with myosins and IQDs, while potentially influencing gene expression through interactions with CAMTAs.
Associate Dean, Serving and Engaging Society Assistant Professor, Departments of Community Health and Epidemiology and Continuing Professional Development and Medical Education Research Scholar, Health Law Institute Dalhousie University Faculty of Medicine Rethinking EDIA in 2024 By the end of this session participants will:
PhD Student, Regan Lab Surveying the Hormonome of Hazelnut Flower Dormancy Hazelnut is an emerging crop in Ontario but elite, European cultivars must adapt to Ontario winters to support local demand. Hazelnut is a winter flowering tree, meaning flowers begin their development in the summer, go dormant over the winter, and bloom in the spring. Brief, early, warm spells are typical of Ontario winters and can signal hazelnut’s male flowers (catkins) to bloom prematurely. Premature bloom makes catkins especially vulnerable to incoming cold weather, damaging pollen and reducing nut yield. To help establish hazelnut as a reliable crop in Ontario, premature catkin bloom must be prevented. Plant hormones are known to regulate flower dormancy and hormones have been manipulated to delay bloom in select crops. This study has surveyed the endogenous levels of canonical plant hormones and their metabolites (the hormonome) of catkins from early, mid, and late-season blooming hazelnut cultivars across a full season of dormancy. This hormonome is the first of its kind within deciduous woody perennials and provides a valuable resource for those studying flower dormancy in fruit crops. Preliminary analysis shows increased ethylene precursor levels in the early blooming cultivar, revealing a potential target pathway for the manipulation of catkin bloom.
Associate Department Head and Associate Professor; Director of Olga Lakela Herbarium, University of Minnesota Duluth Evaluating a drought-driven model for the evolution of obligate asexual reproduction Obligate apomixis -- asexual reproduction by seed, spore, or egg -- has evolved repeatedly across the tree of life, in diverse organisms ranging from animals (such as reptiles, insects, and fishes) to angiosperms and other plants. Despite its many origins, and the intriguing ecological and evolutionary parallels among them, little is known regarding the causes and long-term consequences of this heritable reproductive syndrome. Some studies suggest that drought, or periodic water limitation, could be key to driving the repeated evolution of obligate apomixis. To evaluate the drought hypothesis, my lab is uniting genomic, spatial, environmental, and life history data (across multiple evolutionary and ecological scales), leveraging ferns as a model system. Current estimates indicate that 10–30% of ferns exhibit obligate apomixis, which has evolved repeatedly in xeric and monsoonal environments around the world. Dry environments impose major constraints on plant life histories and the fern life cycle is especially vulnerable. This study is focused primarily on North American desert ferns and integrates reproductive traits (karyotype, gametophyte development, and spore size/number), climate and microhabitat, and phylogenomic data to specifically ask: Does environmental niche predict obligate apomixis or its constituent traits in desert ferns of North America? This work aims to also bridge generational gaps in technical expertise among next-generation researchers for a variety of cutting-edge and classical approaches, thereby stimulating interdisciplinary student-driven research that emphasizes the value and relevance of museum specimens for addressing fundamental biological questions.
Julia Paton, MSc Candidate, Smol Lab Long-term changes in lake ecosystems linked to smelter emissions on the Atikameksheng Anishnawbek First Nations Reserve Mining operations in Sudbury, Ontario, may have caused acidification, metal contamination, and other disturbances on lakes on the Atikameksheng Anishinabek First Nation (AAFN) Reserve. Despite the societal importance of the Reserve’s many lakes, little direct long-term limnological data are available. Here we use paleolimnology and a multi-proxy approach to reconstruct the potential long-term effects of mining operations on water quality and aquatic biota.
Whitefish Lake is a relatively shallow lake that is situated adjacent to the Sacred Lands of the AAFN community and located approximately 15 km southwest of the Vale Copper Cliff Complex. A sediment core was retrieved in September 2022, radioactively dated, and analyzed for geochemistry. Sedimentary geochemical data reconstructions show increased metal inputs linked to mining operations, with arsenic and copper reaching probable effects levels during peak mining emissions, circa 1960s. Further, the sediment chlorophyll a concentration profile records changes similar to mining-impacted lakes of the Sudbury region. Meanwhile, diatom assemblages show only subtle changes in response to mining, indicating that there was no biological evidence of acidification. Round Lake is a relatively deep lake, located approximately 20 km southwest of the Vale Copper Cliff Complex and less than 5 km west of the abandoned Long Lake Gold Mine, which contains over 163,000 m3 of mining tailings. A sediment core was retrieved in September 2022, radioactively dated, and analyzed for geochemistry. Geochemical reconstructions show increased metal inputs linked to mining operations, with arsenic, cadmium, copper, lead, and zinc reaching probable effects levels during peak mining emissions, circa 1960s. Interestingly, and in contrast to Whitefish Lake, Round Lake’s sedimentary chlorophyll a concentration profile showed no change with the onset of mining. The largest shift in biological data shows a striking change in diatom assemblages post-mining; however, these changes were not linked to acidification. This research offers a unique opportunity to collaborate with Indigenous communities and apply western scientific approaches to provide data critical to proper lake management and ultimately protect the societal value of aquatic ecosystems within the Atikameksheng Anishinabek First Nation community. Evan Jones, MSc Candidate, Smol Lab Tracking the long-term limnological impacts of silver mining near Keno City on the traditional territory of the First Nation of Na-Cho Nyäk Dun (Yukon, subarctic Canada) Mining in Northern Canada has caused many major environmental problems; however, historical data are often non-existent. Here, a multi-proxy (metals, bioindicators, pigments) paleolimnological approach is used to reconstruct the historical impacts of mining activity near Keno City, on the traditional land of the First Nation of Na-Cho Nyäk Dun in central Yukon (Canada). Silver was discovered in the Keno region in the early 1900s and intensive mining has taken place ever since.
Christal Lake, a shallow water body, lies near many historical and current mines, and was once the site of a processing mill. A sediment core was retrieved from Christal Lake in September 2022. Geochemical data from the dated sediment core were used to reconstruct metal inputs linked to the mining activity. The largest shift in biological indicators was a striking decline in sedimentary chlorophyll-a concentrations, indicating declining algal populations. Meanwhile, subfossil diatom assemblages only changed subtly in response to mining. There was no biological evidence of acidification, likely due to the neutralizing effect of the carbonate-rich catchment. The Hanson lakes are situated ~10 km from Keno City and are outside the Christal Lake watershed. These lakes are being studied to determine the potential extent of aerial deposition of mining contaminants. A sediment core was retrieved from a basin in the Hanson lakes system in October 2023. Preliminary results indicate that, despite proximity to mines, it is climate that is the major driver of ecological change in this system. Collectively, the data from these two sites help document the long-term impacts of silver mining in this subarctic environment. Dr. Patricia Gillis, Research Scientist, Environment and Climate Change Canada Are Clams Actually Happy? Using Freshwater Mussel Ecotoxicology to Determine What Threatens an Imperiled Group Native freshwater mussels (Unionidae) are an ecologically important group, although their complex lifecycle leaves them vulnerable to a range of hazards. Over 70% of North American mussel species are either endangered, threatened, or in decline and poor water quality is considered to be one of the key contributors to their global decline. Canada’s Recovery Strategies for freshwater mussel Species at Risk recognize that poor water quality can affect conservation efforts and pose a risk to recovery. However, the identification and remediation of specific threats presents a challenge when extrapolating from single contaminant lab-based bioassays to the health of native mussel populations, especially in areas with complex mixtures of anthropogenic inputs. With the goal of broadening our understanding of which contaminants pose a risk to mussels, laboratory studies with a range of chemicals have been undertaken in parallel with wild mussel health and population assessments in anthropogenically-impacted habitats. This seminar will illustrate the joys and challenges of working with this complex canary by providing examples of studies that combine lab and field investigations. The first example is centered on the heightened sensitivity of early life stage mussels to salt and the threat that road salt-laden winter road runoff poses to mussels. The second example demonstrates how urban influences, including municipal wastewater effluent negatively impact freshwater mussels across multiple levels of biological organization. A final example will touch on the ‘Clam Project’, an Indigenous Community led investigation of freshwater mussels in Alberta’s Oil Sands Region.
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