Unraveling the diversity and biological activity of cyanobacteria natural products

加拿大拥有100多万个湖泊，获得了全球20%以上的淡水资源，是地球上相当大一部分饮用水的管理者。在过去的一百年里，淡水生态系统(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给这些生态系统带来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数量增加。蓝藻水华将生物活性化合物的混合物释放到淡水中，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，大多数蓝藻化学物质的化学成分、环境浓度、毒理风险和有益特性都是未知的。我的研究计划将使用创新的策略推动蓝藻化学的发展。代谢组学指导的天然产物发现将以新的化学物质为目标进行结构表征。这将使对特征不佳的蓝藻化学品的全面暴露和生物活性评估成为可能。将表型分析与代谢组学相结合，将确定我的计划提纯的化学物质的分子作用模式。这项研究将挖掘蓝藻，一个未被研究的新化学储藏库，以寻找在农业和医药中应用的新化学物质。它还将支持加拿大监管机构，这些监管机构肩负着管理日益紧张的淡水资源的艰巨任务，而不了解排放到环境中的化学物质的多样性。

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.