The Woods Hole Center for Oceans and Human Health (WHCOHH) will comprise a strong and integrated set of research projects using novel in situ sampling technologies and modeling approaches building on prior research to address how changing climate could influence harmful algal bloom (HAB) dynamics and human exposure to HAB toxins, a serious and global human health threat. The overall objective is to protect public health through enhanced understanding of how climate and oceanic processes affect the intensity and distribution of toxin-producing HABs and to understand the potential health risks from exposure even to low levels of their potent neurotoxins, especially during susceptible stages of life. The Center will focus on two key HAB taxa: Alexandrium catenella, which produces the saxitoxins responsible for paralytic shellfish poisoning (PSP), and Pseudo-nitzschia spp., which produce domoic acid responsible for amnesic shellfish poisoning (ASP) syndrome, both are expanding geographically. Novel, targeted, efficient, and data-rich sampling approaches developed by the applicants and applied in situ in natural settings have revealed new controls of A. catenella population dynamics, and have identified possible new climate links regarding toxic Pseudo- nitzschia species. Project 1 will examine further the physiological and climatic variables affecting these HABs, which may underlie population adaptation in different habitats and different environmental regimes. Project 2 will incorporate these new and fundamental insights on bloom regulation into coupled climate-population models to predict HAB threats under future climate scenarios, a key step toward being able to quantify future risks from this recurrent public health threat. In biomedical studies with the zebrafish model, Project 3 has identified myelination in the developing brain as a target of domoic acid. They will use transgenic zebrafish and single-cell RNA-sequencing to identify the cell-specific mechanisms underlying effects of domoic acid, saxitoxin, and the cyanotoxin anatoxin-a in zebrafish embryos in vivo and will use human iPSC-derived 3D brain systems in vitro to elucidate toxin effects on neural and glial cell differentiation in human cells. Studies also will determine whether prior exposure to ubiquitous persistent organic pollutants may modify effects of subsequent exposure to saxitoxin and domoic acid. All projects will collaborate in modeling to link oceanic processes to human exposure, helping to define the exposure of susceptible human subpopulations and predict the effects of a changing climate. The Community Engagement Core will facilitate integration of the research with education and engagement of resource managers and other stakeholders. We also will improve awareness of emerging HAB issues for the public health community and develop new educational materials and interactive activities for K-12 classrooms, and for health care providers. An Administrative Core will encourage open discussion of planning, integration, communication and enhancing diverse perspectives, and provide rigorous evaluation of progress in all aspects of the program.

Project Narrative The mission of the Woods Hole Center for Oceans and Human Health is to protect the public health by: a) expanding our understanding of how climate and oceanic processes affect the population dynamics of key Harmful Algal Bloom (HAB) species, b) applying this information to predict how climate variability influences HABs and human exposure to toxins, and c) determining the scope and consequences of newly identified effects in the brain from exposure to potent HAB neurotoxins during development. Studies will focus on Alexandrium catenella and Pseudo-nitzschia spp. that produce the potent neurotoxins saxitoxin and domoic acid, respectively. Findings will be communicated, involving resource managers, stakeholders, students, health care providers and the public, to enhance understanding and disease diagnosis and improve public health.