Overview
Project 2 seeks to reveal the diversity, spatial and temporal distribution, and bioactivity of known and undiscovered toxins and other secondary metabolites. This project will use a combination of multi-omics (metagenomics, transcriptomics, metabolomics) to discover and characterize the vast diversity of emerging toxins and bioactive compounds currently invisible to methods used in routine water quality analysis. In contrast to most previous research that has focused on the toxicology of single cyanotoxins, Project 2 will uncover the environmental distribution and biological effects of complex mixtures of cyanotoxins that characterize cyanobacterial harmful algal bloom (cHAB) communities in the field.
Research Team
More Details
Cyanobacterial harmful algal blooms (cHABS) comprise a diverse and dynamic array of photosynthetic and heterotrophic bacterial species with unique biosynthetic potential leading to a vast and underexplored metabolome. Despite this diversity, most efforts over the past 50 years have focused on studying the dynamics of expression and production of the microcystin class of hepatotoxins. These toxins are known to be produced by Microcystis spp., the bloom-forming cyanobacteria responsible for cHABs around the world, including Western Lake Erie (WLE), and have caused illness and/or death in 43 states in the U.S. Most of the available studies focus on microcystins and a few other canonical cyanotoxins; little is known about the bioactivity and harmful effects of other individual cyanotoxins, their mixtures, and the broader landscape of cHAB metabolites. Recent studies indicate that cyanotoxins and their mixtures may play a role in exacerbating nonalcoholic fatty liver disease, inflammatory diseases, and neurodegeneration. These cyanotoxins are produced in complex mixtures of known and unknown metabolites driven by varying abiotic and biotic variables within the cHABs microbiome system. Their effects on human health have motivated our work to develop a toxin forecasting model to help protect the public via detection/surveillance, policy, and environmental regulations.
Goals
- Assess the dangers to public health through an in-depth analysis of cyanotoxins and their combinations produced in WLE cHABs
- Determine the phenotypic and proteomic toxicological effects of the combinations in a manner replicating human in situ exposure.
- Determine the spatiotemporal distribution and environmental factors influencing cyanobacterial communities, specialized metabolites, and their biosynthetic gene clusters
- Pursue a metabologenomics-assisted structural characterization of high-priority molecules, including new toxins and other secondary metabolites
- Identify individual and synergistic effects of natural cyano- and other bacterial toxins and their mixtures using validated whole cell assay systems.
- Benefit toxin prediction models and early forecasting systems, informing the public of their risk when living and recreating in the WLE region while cHABs are active