Unraveling the diversity and biological activity of cyanobacteria natural products

加拿大拥有100多万个湖泊，拥有全球20%以上的淡水资源，是地球上大量饮用水的管理者。在过去的一百年里，淡水生态系统（例如，河流、湖泊和湿地）经历了广泛的环境变化。人口增长、污染、气温升高和栖息地退化对这些生态系统造成的巨大压力是造成这种变化的原因。这种环境变化的一个明显后果是有毒蓝藻水华的频率和规模增加。蓝藻水华向淡水中释放生物活性化合物的混合物，对人类和生态系统健康、野生动物和当地经济产生负面影响。尽管如此，大多数蓝藻化学品的化学性质、环境浓度、毒理学风险和有益特性尚不清楚。我的研究计划将使用创新策略推进蓝藻化学。代谢组学引导的天然产物发现将针对新的化学品进行结构表征。这将使全面的接触和生物活性评估的特点不明确的蓝藻化学品。结合表型分析与代谢组学将确定分子模式的行动，我的程序纯化的化学品。这项研究将挖掘蓝藻，一个未被充分研究的新化学水库，用于农业和医学应用的新化学品。它还将支持加拿大监管机构，这些监管机构在不了解释放到环境中的化学品的多样性的情况下，承担着管理日益紧张的淡水资源的艰巨任务。

With over one-million lakes and access to upwards of 20% of global freshwater resources, Canada is the steward for a significant amount of the planet's drinking water. Over the last one hundred years, freshwater ecosystems (e.g., rivers, lakes and wetlands) have undergone widespread environmental change. Intense pressure on these ecosystems from population growth, pollution, increased temperatures, and habitat degradation are responsible for this change. A visible consequence of this environmental change is the increase in frequency and magnitude of toxic cyanobacteria blooms. Cyanobacteria blooms release mixtures of biologically active compounds into freshwater that negatively impact human and ecosystem health, wildlife, and local economies. Despite this, the chemistry, environmental concentrations, toxicological risks, and beneficial properties of most cyanobacteria chemicals are unknown. My research program will advance cyanobacteria chemistry using innovative strategies. Metabolomics-guided natural product discovery will target novel chemicals for structural characterizations. This will enable comprehensive exposure and biological activity assessments for poorly characterized cyanobacteria chemicals. Combining phenotype assays with metabolomics will determine the molecular modes of action for chemicals purified by my program. This research will mine cyanobacteria, an understudied reservoir of new chemistry, for novel chemicals with applications in agriculture and medicine. It will also support Canadian regulators that have the daunting task of managing increasingly stressed freshwater resources without understanding the diversity of chemicals released into the environment.