J Chem Ecol (2014) 40:218–219 DOI 10.1007/s10886-014-0394-4
COMMENTARY: REFLECTIONS ON 40 YEARS
There’s Something in the Water: Opportunities in Marine Chemical Ecology Julia Kubanek
Published online: 12 March 2014 # Springer Science+Business Media New York 2014 Authors represented in the 40 years of the Journal of Chemical Ecology have been trained in a number of distinct disciplines: traditional chemistry or ecology, molecular biology, animal physiology, agriculture, marine biology, or evolution—to name a few. These diverse perspectives have fostered an interdisciplinary spirit evident when reading articles across the 40 years of the journal and that enriches modern discoveries in chemical ecology. My own participation dates only to the second half of this rich history; yet even during this period chemical ecology has evolved, making the research of the 1990’s barely recognizable to my graduate students. This essay focuses on present challenges and opportunities in marine chemical ecology, an area of substantial growth during the last 20 years. In particular, issues related to the mechanisms of chemically mediated interactions are highlighted. Scientists working in marine chemical ecology have asked numerous questions on the subject of how chemical cues function at a mechanistic level. A fundamental chemistry question has been: which molecules are responsible for deterring consumers, suppressing competitors, protecting against pathogens and parasites, communicating with conspecifics, detecting predators or habitat, and capturing prey? An obvious advance in recent years has been the full structural elucidation of hundreds of complex organic molecules that function as chemical defenses, particularly against consumers and pathogens. Because modern spectroscopic and synthetic techniques now permit definitive assignment of molecular structure including stereochemistry requiring mere micrograms of most complex natural products, answering “which molecules” is rarely out of reach for chemical cues that are reasonably stable and accessible from harvested or cultured marine organisms. However, many chemical cues that are transmitted through water to act as allelopathic agents, mate attractants, or cues for inducing responses to predators appear to be unstable and/or are produced in minute quantities that make it difficult to solve their molecular structures even with modern approaches. For aquatic environments where volatility is not a necessary property for a chemical cue (instead favoring molecules that exhibit at least a modicum of water
J. Kubanek (*) School of Biology and School of Chemistry & Biochemistry, Aquatic Chemical Ecology Center, Georgia Institute of Technology, 310 Ferst Drive, Atlanta, GA 30332-0230, USA e-mail: [email protected]
solubility), there is less pressure than in terrestrial systems for evolution to restrict the molecular size of cues transmitted through the medium. This is evident from the diversity of structural types of waterborne chemical cues including proteins and large functionalized lipids. Yet, most chemical cues transmitted through the water column have yet to be characterized. Increasing spectroscopic power is only part of the solution. Novel spectroscopic techniques that enable identification of compounds within mixtures, including LC/MS, MS- and NMR-based metabolomics, and pure-shift NMR spectroscopy are now being applied to tackle problems of instability, low concentration, and tricky properties such as high water solubility of waterborne chemical cues. With these advances, in the coming decade we can expect to identify full molecular structures of chemical cues for critical marine ecological interactions including competition, mating, cooperation, and induction of chemical defenses. Advances in identifying chemical cues present opportunities for understanding their mechanisms of action. How do marine compounds act at the molecular and cellular levels in target species? While studies of small molecules acting on mammalian targets have long been central to the field of natural product drug discovery, the use of ecologically relevant species in mechanism of action studies is now in ascendency within the field of marine chemical ecology. This focus enables a biochemical understanding of how chemical cues exert their ecological effects, complementary to our maturing understanding of the chemical cues themselves. Typically, chemical cues bind to a cellular receptor causing enzyme-based signal cascades resulting in downstream physiological or behavioral changes in the target organism. However, the chemoreceptors involved in marine chemical ecology are largely unknown, as are the intra- and intercellular pathways connecting chemical cues to their ecological outcomes. In marine chemical ecology, deciphering these receptors and pathways using modern molecular biology and chemical biology approaches will lead to our ability to manipulate sensory responses, control behavior (including of microorganisms), and elucidate biosynthetic pathways for induced chemical defenses. For example, understanding at a molecular level how marine copepod exudates trigger production of toxins by bloom-forming algae could shed light on the biosynthesis of these toxins and allow scientists to manipulate their production.
J Chem Ecol (2014) 40:218–219 Like natural product drugs, chemical cues in marine systems probably affect multiple cellular targets in organisms exposed to these cues. For example, a chemical defense molecule may modulate olfactory or taste chemoreception pathways within a predator resulting in deterrence, as well as decrease predator fitness via toxicity (which itself might involve many pathways). There are typically thousands of potential cellular targets for any given chemical cue, and designing experiments to test individual hypotheses is limited by our imagination, time, and experimental abilities. In contrast, systems biology approaches that simultaneously measure effects on hundreds or thousands of pathways enable us to generate and begin to test hypotheses in a less biased manner. In particular, metabolomics, proteomics, and transcriptomics each allow us to detect alterations in physiology for organisms responding to chemical cues (vs. suitable unexposed controls). These approaches rely on high sample numbers and use of multivariate statistics to reveal metabolites, proteins, and genes whose activities are modulated by ecological interactions. Most such studies are correlative by design, benefitting from carefully designed follow-up experiments aimed at testing more focused hypotheses about direct effects of chemical cues on cellular pathways.
219 Ultimately, understanding the mechanisms of chemical cues in marine systems would require connecting all steps between the molecule produced as a chemical cue by one organism to the altered behavior or physiology of another organism. We are still far from being able to map most ecological interactions this way. Yet, the potential benefits are tantalizing, including to community and ecosystem ecologists who do not normally focus at the molecular level: we could use our understanding of the molecules and pathways involved in ecological interactions to test how climate change (e.g., ocean acidification) will, in the future, alter chemically mediated predator–prey interactions and thus marine community structure; we could apply this understanding to more intelligently predict and then test pharmacological properties of marine natural products; we could genetically manipulate organisms (e.g., bacteria or harmful algae) to respond differently to chemical cues and other environmental triggers and then test effects on ecosystem function. At times, the different languages of chemists and biologists have seemed to present a barrier in our field. This is much less the case for 21st century chemical ecologists, and the resulting opportunities are exciting.
COMMENTARY: REFLECTIONS ON 40 YEARS
There’s Something in the Water: Opportunities in Marine Chemical Ecology Julia Kubanek
Published online: 12 March 2014 # Springer Science+Business Media New York 2014 Authors represented in the 40 years of the Journal of Chemical Ecology have been trained in a number of distinct disciplines: traditional chemistry or ecology, molecular biology, animal physiology, agriculture, marine biology, or evolution—to name a few. These diverse perspectives have fostered an interdisciplinary spirit evident when reading articles across the 40 years of the journal and that enriches modern discoveries in chemical ecology. My own participation dates only to the second half of this rich history; yet even during this period chemical ecology has evolved, making the research of the 1990’s barely recognizable to my graduate students. This essay focuses on present challenges and opportunities in marine chemical ecology, an area of substantial growth during the last 20 years. In particular, issues related to the mechanisms of chemically mediated interactions are highlighted. Scientists working in marine chemical ecology have asked numerous questions on the subject of how chemical cues function at a mechanistic level. A fundamental chemistry question has been: which molecules are responsible for deterring consumers, suppressing competitors, protecting against pathogens and parasites, communicating with conspecifics, detecting predators or habitat, and capturing prey? An obvious advance in recent years has been the full structural elucidation of hundreds of complex organic molecules that function as chemical defenses, particularly against consumers and pathogens. Because modern spectroscopic and synthetic techniques now permit definitive assignment of molecular structure including stereochemistry requiring mere micrograms of most complex natural products, answering “which molecules” is rarely out of reach for chemical cues that are reasonably stable and accessible from harvested or cultured marine organisms. However, many chemical cues that are transmitted through water to act as allelopathic agents, mate attractants, or cues for inducing responses to predators appear to be unstable and/or are produced in minute quantities that make it difficult to solve their molecular structures even with modern approaches. For aquatic environments where volatility is not a necessary property for a chemical cue (instead favoring molecules that exhibit at least a modicum of water
J. Kubanek (*) School of Biology and School of Chemistry & Biochemistry, Aquatic Chemical Ecology Center, Georgia Institute of Technology, 310 Ferst Drive, Atlanta, GA 30332-0230, USA e-mail: [email protected]
solubility), there is less pressure than in terrestrial systems for evolution to restrict the molecular size of cues transmitted through the medium. This is evident from the diversity of structural types of waterborne chemical cues including proteins and large functionalized lipids. Yet, most chemical cues transmitted through the water column have yet to be characterized. Increasing spectroscopic power is only part of the solution. Novel spectroscopic techniques that enable identification of compounds within mixtures, including LC/MS, MS- and NMR-based metabolomics, and pure-shift NMR spectroscopy are now being applied to tackle problems of instability, low concentration, and tricky properties such as high water solubility of waterborne chemical cues. With these advances, in the coming decade we can expect to identify full molecular structures of chemical cues for critical marine ecological interactions including competition, mating, cooperation, and induction of chemical defenses. Advances in identifying chemical cues present opportunities for understanding their mechanisms of action. How do marine compounds act at the molecular and cellular levels in target species? While studies of small molecules acting on mammalian targets have long been central to the field of natural product drug discovery, the use of ecologically relevant species in mechanism of action studies is now in ascendency within the field of marine chemical ecology. This focus enables a biochemical understanding of how chemical cues exert their ecological effects, complementary to our maturing understanding of the chemical cues themselves. Typically, chemical cues bind to a cellular receptor causing enzyme-based signal cascades resulting in downstream physiological or behavioral changes in the target organism. However, the chemoreceptors involved in marine chemical ecology are largely unknown, as are the intra- and intercellular pathways connecting chemical cues to their ecological outcomes. In marine chemical ecology, deciphering these receptors and pathways using modern molecular biology and chemical biology approaches will lead to our ability to manipulate sensory responses, control behavior (including of microorganisms), and elucidate biosynthetic pathways for induced chemical defenses. For example, understanding at a molecular level how marine copepod exudates trigger production of toxins by bloom-forming algae could shed light on the biosynthesis of these toxins and allow scientists to manipulate their production.
J Chem Ecol (2014) 40:218–219 Like natural product drugs, chemical cues in marine systems probably affect multiple cellular targets in organisms exposed to these cues. For example, a chemical defense molecule may modulate olfactory or taste chemoreception pathways within a predator resulting in deterrence, as well as decrease predator fitness via toxicity (which itself might involve many pathways). There are typically thousands of potential cellular targets for any given chemical cue, and designing experiments to test individual hypotheses is limited by our imagination, time, and experimental abilities. In contrast, systems biology approaches that simultaneously measure effects on hundreds or thousands of pathways enable us to generate and begin to test hypotheses in a less biased manner. In particular, metabolomics, proteomics, and transcriptomics each allow us to detect alterations in physiology for organisms responding to chemical cues (vs. suitable unexposed controls). These approaches rely on high sample numbers and use of multivariate statistics to reveal metabolites, proteins, and genes whose activities are modulated by ecological interactions. Most such studies are correlative by design, benefitting from carefully designed follow-up experiments aimed at testing more focused hypotheses about direct effects of chemical cues on cellular pathways.
219 Ultimately, understanding the mechanisms of chemical cues in marine systems would require connecting all steps between the molecule produced as a chemical cue by one organism to the altered behavior or physiology of another organism. We are still far from being able to map most ecological interactions this way. Yet, the potential benefits are tantalizing, including to community and ecosystem ecologists who do not normally focus at the molecular level: we could use our understanding of the molecules and pathways involved in ecological interactions to test how climate change (e.g., ocean acidification) will, in the future, alter chemically mediated predator–prey interactions and thus marine community structure; we could apply this understanding to more intelligently predict and then test pharmacological properties of marine natural products; we could genetically manipulate organisms (e.g., bacteria or harmful algae) to respond differently to chemical cues and other environmental triggers and then test effects on ecosystem function. At times, the different languages of chemists and biologists have seemed to present a barrier in our field. This is much less the case for 21st century chemical ecologists, and the resulting opportunities are exciting.
