The goal of Associate Program 2 is to use ecological insights to guide the discovery of novel natural products with biological activity against a targeted group of diseases critical to developing nations and to the United States. In complex environments such as near-shore marine habitats, secondary metabolism has evolved over billions of years in response to intense selection pressure on organisms to solve critical challenges associated with survival and reproduction. In particular, tropical coral reefs host diverse microorganisms, algae, and invertebrates that use chemical cues and chemical defenses as a language driving interactions among and within species. Small organic molecules that are critical in mediating ecological interactions are strong candidates for new medicines targeting infectious disease caused by bacteria, fungi, and parasites, in addition to cancer and neurological disorders. We will explore understudied coral reef organisms including rare species of marine algae and invertebrates and microbes associated with algal and coral surfaces. We will apply ecological assays to uncover novel secondary metabolism, extending our previous work testing for antimicrobial, antiherbivore, and allelopathic compounds by adding microbial overlay and challenge assays to seek chemically rich microbes specialized as pathogens, mutualists, or commensals that produce unique secondary metabolites due to complex ecological interactions. Pursuit of lead drug molecules will be based on prioritized activity in a series of pharmacological screens relevant to infectious disease, tropical neglected disease, cancer, and neurodegenerative and CNS disorders. Identification of novel natural product structures will utilize modern spectroscopic techniques, leading to preclinical studies. Once our aims are met, we will have contributed novel pharmaceutical leads to the biomedical research community;revealed new molecular scaffolds and receptor-ligand interactions to the chemistry and chemical biology communities;learned new lessons on the roles of chemical cues and chemical defenses among marine macro- and microorganisms; applied new metabolomic and metabolic networking approaches to studying secondary metabolism in marine organisms;and trained a generation of scientific personnel in the U.S. and the South Pacific.

National Institute of Health (NIH)
Fogarty International Center (FIC)
Research Program--Cooperative Agreements (U19)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-BCMB-H (50))
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Georgia Institute of Technology
United States
Zip Code
Brooker, Rohan M; Brandl, Simon J; Dixson, Danielle L (2016) Cryptic effects of habitat declines: coral-associated fishes avoid coral-seaweed interactions due to visual and chemical cues. Sci Rep 6:18842
Dell, Claire L A; Longo, Guilherme O; Hay, Mark E (2016) Positive Feedbacks Enhance Macroalgal Resilience on Degraded Coral Reefs. PLoS One 11:e0155049
Jensen, Paul R (2016) Natural Products and the Gene Cluster Revolution. Trends Microbiol 24:968-977
Tang, Xiaoyu; Li, Jie; Millán-Aguiñaga, Natalie et al. (2015) Identification of Thiotetronic Acid Antibiotic Biosynthetic Pathways by Target-directed Genome Mining. ACS Chem Biol 10:2841-9
Jensen, Paul R; Moore, Bradley S; Fenical, William (2015) The marine actinomycete genus Salinispora: a model organism for secondary metabolite discovery. Nat Prod Rep 32:738-51
Choi, Eun Ju; Nam, Sang-Jip; Paul, Lauren et al. (2015) Previously Uncultured Marine Bacteria Linked to Novel Alkaloid Production. Chem Biol 22:1270-9
Duncan, Katherine R; Crüsemann, Max; Lechner, Anna et al. (2015) Molecular networking and pattern-based genome mining improves discovery of biosynthetic gene clusters and their products from Salinispora species. Chem Biol 22:460-71
Clements, Cody S; Hay, Mark E (2015) Competitors as accomplices: seaweed competitors hide corals from predatory sea stars. Proc Biol Sci 282:
Dixson, Danielle L; Abrego, David; Hay, Mark E (2014) Reef ecology. Chemically mediated behavior of recruiting corals and fishes: a tipping point that may limit reef recovery. Science 345:892-7
Rasher, Douglas B; Hay, Mark E (2014) Competition induces allelopathy but suppresses growth and anti-herbivore defence in a chemically rich seaweed. Proc Biol Sci 281:20132615

Showing the most recent 10 out of 42 publications