Proposal Summary
Harmful algal blooms (cyanoHABs), dense proliferations of toxic cyanobacterial metabolites due to
eutrophication of freshwater, are a leading threat towards drinking water. CyanoHABs impact human health in a
multifaceted way through acute and chronic exposure, aerosolization, economic loss, and reduction in access to
natural resources. Some metabolites produced in cyanoHABs are well known such as microcystins and
saxitoxins, yet countless others remain unidentified. Advances in DNA sequencing and biosynthetic gene cluster
(BGC) mining have revealed the genomic basis and origin of a novel suite of metabolites amongst cyanoHABs,
yet current research remains focused on canonical cyanotoxins. Additionally, recent work indicates that many
commonly produced cyanopeptides have unknown toxic synergistic effects when produced in combination.
These insights suggest that studies of individual cyanotoxins and cyanopeptides on human health do not reflect
the composite health risk associated with natural bloom samples. Thus, unanswered questions remain about the
effects of toxic cyanobacterial metabolites when produced as mixtures in cyanoHABs. Moreover, the
environmental factors driving the production of these toxic metabolites remains poorly understood. Our goal is
to identify the effects of cyanopeptide mixtures on an array of human cell lines and identify the mechanistic basis
for toxin production in cyanoHABs using a nine-year, multi-omic time series from Western Lake Erie (WLE),
where cyanoHABs have threatened the drinking water supply for decades. Determining conserved
cyanobacterial biosynthetic patterns in the field through metagenomic, metatranscriptomic, and metabolomic
analysis will enable improved monitoring strategies to protect public health in and around WLE and globally.
Furthermore, we plan to model these data to identify environmental and physiochemical parameters that
stimulate the production of toxic cyanobacterial metabolites in WLE cyanoHABs. We anticipate these efforts will
catalyze the production of enhanced risk assessment models that consider the combined risks of other toxic
metabolites beyond common cyanotoxins like microcystins. Throughout this study, we will bridge field and
laboratory studies using multi-omic and bioassay techniques to redefine “toxicity” in cyanoHABs by identifying
additional metabolites and metabolite combinations that pose unrecognized threats to human health. Overall,
we hypothesize that changes in toxic metabolite composition across spatiotemporal gradients correspond with
fluctuating cyanobacterial communities within cyanoHABs, representing biosynthetic adaptations and novel
threats towards human health. Ultimately, the development of such models and frameworks for cyanoHABs have
the potential to produce highly resolved risk assessment models for cyanoHABs around the world, thereby
protecting people and natural resources from the effects of these catastrophic events and informing prevention
and management strategies.