An Examination of Current Approaches to Integrative Indigenous and Western Knowledge System Implementation in Water Research and Management: A Case Study Encompassing the Colonized Geographies of Canada, Australia, New Zealand, and the United States

The commodification of natural resources and the pursuit of continuous growth has resulted in environmental degradation, depletion, and disparity in access to these life-sustaining resources, including water. Utility-based objectification and exploitation of water in some societies has brought us to the brink of crisis through an apathetic disregard for present and future generations. The ongoing depletion and degradation of the world’s water sources, coupled with a reliance on Western knowledge and the continued omission of Indigenous knowledge to manage our relationship with water has unduly burdened many, but particularly so for Indigenous communities. The goal of my thesis research is to call attention to and advance the value and validity of using both Indigenous and Western knowledge systems (also known as Two-Eyed Seeing) in water research and management to better care for water. To achieve this goal, I used a combined systematic and realist review method to identify and synthesize the peer-reviewed, integrative water literature, followed by semi-structured interviews with first authors of the exemplars from the included literature to identify the challenges and insights that researchers have experienced in conducting integrative water research. Findings suggest that these authors recognize that many previous attempts to integrate Indigenous knowledges have been tokenistic rather than meaningful, and that new methods for knowledge implementation are needed. Community-based participatory research methods, and the associated tenets of balancing power, fostering trust, and community ownership over the research process, emerged as a pathway towards the meaningful implementation of Indigenous and Western knowledge systems. Data also indicate that engagement and collaborative governance structures developed from a position of mutual respect are integral to the realization of a given project. The recommendations generated from these findings offer support for future Indigenous-led research and partnerships through the identification and examination of approaches that facilitate the meaningful implementation of Indigenous and Western knowledge systems in water research and management. Asking Western science questions and seeking Indigenous science solutions does not appear to be working; instead, the co-design of research projects and asking questions directed at the problem rather than the solution better lends itself to the strengths of Indigenous science.

Design and Synthesis of Acridine-Based Macrocyclic G-Quadruplex DNA Ligands

DNA sequences that are rich in the guanine nucleic base possess the ability to fold into higher order structures called G-quadruplexes. These higher level structures are formed as a result of two sets of four guanine bases hydrogen-bonding together in a planar arrangement called a guanine quartet. Guanine quartets subsequently stack upon each other to form quadruplexes. G-quadruplexes are mainly localized in telomeres as well as in oncogene promoters. One unique and promising therapeutic approach against cancer involves targeting and stabilizing G-quadruplexes with small molecules, generally in order to suppress oncogene expression and telomerase enzyme activity; the latter has been found to contribute to “out-of control” cell growth in ca. 80-85% of all cancer cells and primary tumours while being absent in normal somatic cells. In this work, we present efforts towards designing and synthesizing acridine-based macrocycles (Mh) and (Mb) with the purpose of providing potential G4 ligands that are suited for selective binding to G4 vs. duplex DNA, and stabilize G-quadruplex structures. Two ligands described in this study include an acridine core which provides an aromatic surface capable of π-π interactions with the surface of G-quadruplexes. The successful synthesis of 4,5-diaminoacridine is described in chapter 2, as an essential fragment of the macrocycles (Mh) and (Mb). In order to investigate the synthetic method for macrocyclization, model compounds composing almost half of the designed macrocycles were explored. As discussed in chapter 3, the synthesis of the model compound for (Mb) turned out to be challenging. However, as a step towards the synthesis of (Mh), the synthesis of the hydrogen-containing model compound, which is almost half of the desired macrocycle (Mh) was achieved in our group and proved to be promising.