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The sesquiterpenoid abscisic acid (ABA) mediates an assortment of responses across a variety of king- doms including both higher plants and animals. In plants, where most is known, a linear core ABA signaling pathway has been identified. However, the complexity of ABA-dependent gene expression suggests that ABA functions through an intricate network. Here, using systems biology approaches that focused on genes transcriptionally regulated by ABA, we defined an ABA signaling network of over 500 interactions among 138 proteins. This map greatly expanded ABA core signaling but was still manageable for systematic analysis. For example, functional analysis was used to identify an ABA module centered on two sucrose nonfermenting (SNF)-like kinases. We also used coexpression anal- ysis of interacting partners within the network to un- cover dynamic subnetwork structures in response to different abiotic stresses. This comprehensive ABA resource allows for application of approaches to un- derstanding ABA functions in higher plants. 


Lumba S, Toh S, Handfield L-F, Swan M, Liu R, Youn J-Y, et al (2014). Dev Cell  29: 360–372






A Mesoscale Abscisic Acid Hormone Interactome Reveals a Dynamic Signaling Landscape in Arabidopsis 


Strigolactones are terpenoid-based plant hormones that act as communication signals within a plant, between plants and fungi, and between parasitic plants and their hosts. Here we show that an active enantiomer form of the strigolactone GR24, the germination stimulant karrikin, and a number of structurally related small molecules called cotylimides all bind the HTL/KAI2 α/β hydrolase in Arabidopsis. Strigolactones and cotylimides also promoted an interaction between HTL/KAI2 and the F-box protein MAX2 in yeast. Identification of this chemically dependent protein-protein interaction prompted the development of a yeast-based, high-throughput chemical screen for potential strigolactone mimics. Of the 40 lead compounds identified, three were found to have in planta strigolactone activity using Arabidopsis-based assays. More importantly, these three compounds were all found to stimulate suicide germination of the obligate parasitic plant Striga hermonthica. These results suggest that screening strategies involving yeast/Arabidopsis models may be useful in combating parasitic plant infestations.



Toh S, Holbrook-Smith D. Stokes M, Tsuchiya Y. McCourt P (2014). Chem Biol  21: 988-98



Detection of parasitic plant suicide germination compounds using a high-throughput Arabidopsis HTL/KAI2 strigolactone perception system.

Review: Towards personalized agriculture: what chemical genomics can bring to plant biotechnology.

In contrast to the dominant drug paradigm in which compounds were developed to "fit all," new models focused around personalized medicine are appearing in which treatments are developed and customized for individual patients. The agricultural biotechnology industry (Ag-biotech) should also think about these new personalized models. For example, most common herbicides are generic in action, which led to the development of genetically modified crops to add specificity. The ease and accessibility of modern genomic analysis, when wedded to accessible large chemical space, should facilitate the discovery of chemicals that are more selective in their utility. Is it possible to develop species-selective herbicides and growth regulators? More generally put, is plant research at a stage where chemicals can be developed that streamline plant development and growth to various environments? We believe the advent of chemical genomics now opens up these and other opportunities to "personalize" agriculture. Furthermore, chemical genomics does not necessarily require genetically tractable plant models, which in principle should allow quick translation to practical applications. For this to happen, however, will require collaboration between the Ag-biotech industry and academic labs for early stage research and development, a situation that has proven very fruitful for Big Pharma.


Stokes M E, McCourt P. Front Plant Sci. (2014) 5: 344.

Greatest Hits: Presents a selection of papers published in Nature Chemical Biology over the past decade that reflect the diversity and excitement of chemical biology research.



Greenest Probe: Chemical probe development efforts often focus on animal targets, but recent high-throughput screens in plants have also yielded useful chemical probes: the cotylimides, found by McCourt and colleagues, modulate levels of strigolactone, a plant hormone and allelochemical that promotes parasitic plant growth.


Structure-function analysis identifies highly sensitive strigolactone receptors in Striga


Strigolactones are naturally occurring signaling molecules that affect plant development, fungi-plant interactions, and parasitic plant infestations. We characterized the function of 11 strigolactone receptors from the parasitic plant Striga hermonthica using chemical and structural biology. We found a clade of polyspecific receptors, including one that is sensitive to picomolar concentrations of strigolactone. A crystal structure of a highly sensitive strigolactone receptor from Striga revealed a larger binding pocket than that of the Arabidopsis receptor, which could explain the increased range of strigolactone sensitivity. Thus, the sensitivity of Striga to strigolactones from host plants is driven by receptor sensitivity. By expressing strigolactone receptors in Arabidopsis, we developed a bioassay that can be used to identify chemicals and crops with altered strigolactone levels.


Toh S, Holbrook-Smith D, Stogios P, Onopriyenko O, Lumba S, Tsuchiya Y, Savchenko A, McCourt P. Science (2015) 350:203-7.



PARASITIC PLANTS. Probing strigolactone receptors in Striga hermonthica with fluorescence


Elucidating the signaling mechanism of strigolactones has been the key to controlling the devastating problem caused by the parasitic plant Striga hermonthica. To overcome the genetic intractability that has previously interfered with identification of the strigolactone receptor, we developed a fluorescence turn-on probe, Yoshimulactone Green (YLG), which activates strigolactone signaling and illuminates signal perception by the strigolactone receptors. Here we describe how strigolactones bind to and act via ShHTLs, the diverged family of α/β hydrolase-fold proteins in Striga. Live imaging using YLGs revealed that a dynamic wavelike propagation of strigolactone perception wakes up Striga seeds. We conclude that ShHTLs function as the strigolactone receptors mediating seed germination in Striga. Our findings enable access to strigolactone receptors and observation of the regulatory dynamics for strigolactone signal transduction in Striga.


Tsuchiya Y, Yoshimura M, Sato Y, Kuwata K, Toh S, Holbrook-Smith D, Zhang H, McCourt P, Itami K, Kinoshita T, Hagihara S. Science (2015) 349:864-8.



Small-molecule antagonists of germination of the parasitic plant Striga hermonthica.


Striga spp. (witchweed) is an obligate parasitic plant that attaches to host roots to deplete them of nutrients. In Sub-Saharan Africa, the most destructive Striga species, Striga hermonthica, parasitizes major food crops affecting two-thirds of the arable land and over 100 million people. One potential weakness in the Striga infection process is the way it senses the presence of a host crop. Striga only germinates in the presence of the plant hormone strigolactone, which exudes from a host root. Hence small molecules that perturb strigolactone signaling may be useful tools for disrupting the Striga lifecycle. Here we developed a chemical screen to suppress strigolactone signaling in the model plant Arabidopsis. One compound, soporidine, specifically inhibited a S. hermonthica strigolactone receptor and inhibited the parasite's germination. This indicates that strigolactone-based screens using Arabidopsis are useful in identifying lead compounds to combat Striga infestations.


Holbrook-Smith D, Toh S, Tsuchiya Y, McCourt P. Nat Chem Biol. (2016)  12, 724–729

Yanoyama, K. Nat Chem Biol (2016) 2, 658–659.



Farnesylation mediates brassinosteroid biosynthesis to negatively regulate abscisic acid responses in Arabidopsis


Protein farnesylation is a post-translational modification involving the addition of a 15-carbon farnesyl isoprenoid to the carboxy terminus of select proteins(1-3). Although the roles of this lipid modification are clear in both fungal and animal signalling, many of the mechanistic functions of farnesylation in plant signalling are still unknown. Here, we show that CYP85A2, the cytochrome P450 enzyme that performs the last step in brassinosteroid biosynthesis (conversion of castasterone to brassinolide)(4), must be farnesylated to function in Arabidopsis. Loss of either CYP85A2 or CYP85A2 farnesylation results in reduced brassinolide accumulation and increased plant responsiveness to the hormone abscisic acid (ABA) and overall drought tolerance, explaining previous observations(5). This result not only directly links farnesylation to brassinosteroid biosynthesis but also suggests new strategies to maintain crop yield under challenging climatic conditions.


Northey JG, Liang S, Jamshed M, Deb S, Foo E, Reid JB, McCourt P, Samuel MA. Nat Plants. (2016)  doi: 10.1038/nplants.2016.114.

The perception of strigolactones in vascular plants.

Small-molecule hormones play central roles in plant development, ranging from cellular differentiation and organ formation to developmental response instruction in changing environments. A recently discovered collection of related small molecules collectively called strigolactones are of particular interest, as these hormones also function as ecological communicators between plants and fungi and between parasitic plants and their hosts. Advances from model plant systems have begun to unravel how, as a hormone, strigolactone is perceived and transduced. In this Review, we summarize this information and examine how understanding strigolactone hormone signaling is leading to insights into parasitic plant infections. We specifically focus on how the development of chemical probes can be used in combination with model plant systems to dissect strigolactone's perception in the parasitic plant Striga hermonthica. This information is particularly relevant since Striga is considered one of the largest impediments to food security in sub-Saharan Africa.

​Lumba S, Holbrook-Smith D, McCourt P. Nat Chem Biol (2017)  13 ,599-606

Review: Found in Translation: Applying Lessons from Model Systems to Strigolactone Signaling in Parasitic Plants

Strigolactones (SLs) are small molecules that act as endogenous hormones to regulate plant development as well as exogenous cues that help parasitic plants to infect their hosts. Given that parasitic plants are experimentally challenging systems, researchers are using two approaches to understand how they respond to host-derived SLs. The first involves extrapolating information on SLs from model genetic systems to dissect their roles in parasitic plants. The second uses chemicals to probe SL signaling directly in the parasite Striga hermonthica. These approaches indicate that parasitic plants have co-opted a family of α/β hydrolases to perceive SLs. The importance of this genetic and chemical information cannot be overstated since parasitic plant infestations are major obstacles to food security in the developing world.

Lumba S, Subha A., McCourt P. Trends in Biochem Sci. (2017) doi: 10.1016/j.tibs.2017.04.006. [Epub ahead of print



REVIEW: Chemical genetics and strigolactone perception

Strigolactones (SLs) are a collection of related small molecules that act as hormones in plant growth and development. Intriguingly, SLs also act as ecological communicators between plants and mycorrhizal fungi and between host plants and a collection of parasitic plant species. In the case of mycorrhizal fungi, SLs exude into the soil from host roots to attract fungal hyphae for a beneficial interaction. In the case of parasitic plants, however, root-exuded SLs cause dormant parasitic plant seeds to germinate, thereby allowing the resulting seedling to infect the host and withdraw nutrients. Because a laboratory-friendly model does not exist for parasitic plants, researchers are currently using information gleaned from model plants like Arabidopsis in combination with the chemical probes developed through chemical genetics to understand SL perception of parasitic plants. This work first shows that understanding SL signaling is useful in developing chemical probes that perturb SL perception. Second, it indicates that the chemical space available to probe SL signaling in both model and parasitic plants is sizeable. Because these parasitic pests represent a major concern for food insecurity in the developing world, there is great need for chemical approaches to uncover novel lead compounds that perturb parasitic plant infections

Lumba S, Bunsick M, McCourt P.  F1000 Research (2017)  6:975 (doi: 10.12688/f1000research.11379.1)

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