The overall objective of the proposed research is to elucidate the molecular mechanisms by which short-term exposure to harmful algal bloom (HAB) toxins and marine toxicants during development causes physiological and neurological abnormalities later in life. It is now well known that the early life environment can have a profound effect on the health of adults (the developmental origins of health and disease). However, the mechanisms by which developmental exposure elicits effects later in life are not understood. The central hypothesis of this research is that embryonic exposure to certain marine toxins or toxicants alters epigenetic programming, leading to long-term effects on gene expression in adult tissues and ultimately contributing to altered neurobehavioral function in adults. We will conduct studies to identify a core set of genes that show long-term transcriptional changes due to changes in the early life chemical environment and identify their epigenetic signature to determine the mechanistic link between adult phenotype and early life exposures. These studies will be conducted using zebrafish, a powerful model organism for research on developmental mechanisms.
In Aim 1, we will test the hypothesis that developmental exposure to HAB toxins (saxitoxin, domoic acid) and toxicants (PCB126, PCB153) causes later life changes in gene expression and behavior.
In Aim 2, we will test the hypothesis that adult effects resulting from developmental exposure to HAB toxins and toxicants are caused by epigenetic reprogramming of gene expression, focusing on altered DNA methylation and microRNA expression.
In Aim 3, we will determine whether the proximal mechanisms involving receptors and ion channels known to be responsible for the acute effects of these chemicals are also involved in the delayed effects seen in adults exposed to chemicals during development. This research will identify molecular bases for adult effects occurring after developmental exposure to important HAB toxins and marine toxicants, and determine whether there are similar or convergent epigenetic mechanisms involved.

Public Health Relevance

Project 3 addresses an important public health problem: effects of early life (embryonic / perinatal) exposure to marine chemicals on neurological development and later-life function. The proposed studies will provide an understanding of the long-term health consequences of developmental exposure to marine toxins and toxicants, critical in assessing public health risks associated with widespread exposure to these chemicals.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Program Projects (P01)
Project #
5P01ES021923-03
Application #
8708090
Study Section
Special Emphasis Panel (ZES1-LKB-J)
Project Start
Project End
Budget Start
2014-08-01
Budget End
2015-07-31
Support Year
3
Fiscal Year
2014
Total Cost
$108,797
Indirect Cost
$43,607
Name
Woods Hole Oceanographic Institution
Department
Type
DUNS #
001766682
City
Woods Hole
State
MA
Country
United States
Zip Code
02543
Fernandes, Luciano F; Hubbard, Katherine A; Richlen, Mindy L et al. (2014) Diversity and toxicity of the diatom Pseudo-nitzschia Peragallo in the Gulf of Maine, Northwestern Atlantic Ocean. Deep Sea Res Part 2 Top Stud Oceanogr 103:139-162
Butman, Bradford; Aretxabaleta, Alfredo L; Dickhudt, Patrick J et al. (2014) Investigating the importance of sediment resuspension in Alexandrium fundyense cyst population dynamics in the Gulf of Maine. Deep Sea Res Part 2 Top Stud Oceanogr 103:79-95
Pilskaln, C H; Hayashi, K; Keafer, B A et al. (2014) Benthic nepheloid layers in the Gulf of Maine and Alexandrium cyst inventories. Deep Sea Res Part 2 Top Stud Oceanogr 103:55-65
Brosnahan, Michael L; Farzan, Shahla; Keafer, Bruce A et al. (2014) Complexities of bloom dynamics in the toxic dinoflagellate Alexandrium fundyense revealed through DNA measurements by imaging flow cytometry coupled with species-specific rRNA probes. Deep Sea Res Part 2 Top Stud Oceanogr 103:185-198
Koch, F; Kang, Y; Villareal, T A et al. (2014) A novel immunofluorescence flow cytometry technique detects the expansion of brown tides caused by Aureoumbra lagunensis to the Caribbean Sea. Appl Environ Microbiol 80:4947-57
Anderson, Donald M; Keafer, Bruce A; Kleindinst, Judith L et al. (2014) Alexandrium fundyense cysts in the Gulf of Maine: long-term time series of abundance and distribution, and linkages to past and future blooms. Deep Sea Res Part 2 Top Stud Oceanogr 103:6-26
Anderson, Donald M; Couture, Darcie A; Kleindinst, Judith L et al. (2014) Understanding interannual, decadal level variability in paralytic shellfish poisoning toxicity in the Gulf of Maine: the HAB Index. Deep Sea Res Part 2 Top Stud Oceanogr 103:264-276
Kleindinst, Judith L; Anderson, Donald M; McGillicuddy Jr, Dennis J et al. (2014) Categorizing the severity of paralytic shellfish poisoning outbreaks in the Gulf of Maine for forecasting and management. Deep Sea Res Part 2 Top Stud Oceanogr 103:277-287
Deeds, Jonathan R; Petitpas, Christian M; Shue, Vangie et al. (2014) PSP toxin levels and plankton community composition and abundance in size-fractionated vertical profiles during spring/summer blooms of the toxic dinoflagellate Alexandrium fundyense in the Gulf of Maine and on Georges Bank, 2007, 2008, and 2010: 1. Toxin Deep Sea Res Part 2 Top Stud Oceanogr 103:329-349
McGillicuddy Jr, D J; Brosnahan, M L; Couture, D A et al. (2014) A red tide of Alexandrium fundyense in the Gulf of Maine. Deep Sea Res Part 2 Top Stud Oceanogr 103:174-184

Showing the most recent 10 out of 15 publications