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Lawrence, T. J.

Publications and source records attributed to Lawrence, T. J..

2 recordsLinked to original sources

Sphagnum peat moss thermotolerance is modulated by the microbiome

Sphagnum peat mosses is a major genus that is common to peatland ecosystems, where the species contribute to key biogeochemical processes including the uptake and long-term storage of atmospheric carbon. Warming threatens Sphagnum mosses and the peatland ecosystems in which they reside, potentially affecting the fate of vast global carbon stores. The competitive success of Sphagnum species is attributed in part to their symbiotic interactions with microbial associates. These microbes have the potential to rapidly respond to environmental change, thereby helping their host plants survive under changing environmental conditions. To investigate the importance of microbiome thermal origin on host plant thermotolerance, we mechanically separated the microbiome from Sphagnum plants residing in a whole-ecosystem warming study, transferred the component microbes to germ-free plants, and exposed the new hosts to temperature stress. Although warming decreased plant photosynthesis and growth in germ-free plants, the addition of a microbiome from a thermal origin that matched the experimental temperature completely restored plants to their pre-warming growth rates. Metagenome and metatranscriptome analyses revealed that warming altered microbial community structure, including the composition of key cyanobacteria symbionts, in a manner that induced the plant heat shock response, especially the Hsp70 family and jasmonic acid production. The plant heat shock response could be induced even without warming, suggesting that the warming-origin microbiome provided the host plant with thermal preconditioning. Together, our findings show that the microbiome can transmit thermotolerant phenotypes to host plants, providing a valuable strategy for rapidly responding to environmental change.

plant biology↗

Targeting tRNA-Synthetase Interactions towards Novel Therapeutic Discovery Against Eukaryotic Pathogens

The development of chemotherapies against eukaryotic pathogens is especially challenging because of both the evolutionary conservation of drug targets between host and parasite, and the evolution of strain-dependent drug resistance. There is a strong need for new nontoxic drugs with broad-spectrum activity against trypanosome parasites such as Leishmania and Trypanosoma. A relatively untested approach is to target macromolecular interactions in parasites rather than small molecular interactions, under the hypothesis that the features specifying macromolecular interactions diverge more rapidly through coevolution. We computed tRNA Class-Informative Features in humans and eight clades of trypanosomes, identifying parasite-specific informative features (including base-pairs and base mis-pairs) that are broadly conserved over approximately 250 million years of trypanosome evolution. Validating these observations, we demonstrated biochemically that tRNA:aminoacyl-tRNA synthetase interactions are a promising target for anti-trypanosomal drug discovery. From a marine natural products extract library, we identified several fractions with inhibitory activity toward Leishmania major alanyl-tRNA synthetase (AlaRS) but no activity against the human homolog. These marine natural products extracts showed cross-reactivity towards Trypanosoma cruzi AlaRS indicating the broad-spectrum potential of our network predictions. These findings support a systems biology model in which combination chemotherapies that target multiple tRNA-synthetase interactions should be comparatively less prone to the emergence of resistance than conventional single drug therapies.\n\nAuthor SummaryTrypanosome parasites pose a significant health risk worldwide. Conventional drug development strategies have proven challenging given the high conservation between humans and pathogens, with off-target toxicity being a common problem. Protein synthesis inhibitors have historically been an attractive target for antimicrobial discovery against bacteria, and more recently for eukaryotic pathogens. Here we propose that exploiting pathogen-specific tRNA-synthetase interactions offers the potential for highly targeted drug discovery. To this end, we improved tRNA gene annotations in trypanosome genomes, identified functionally informative trypanosome-specific tRNA features, and showed that these features are highly conserved over approximately 250 million years of trypanosome evolution. Highlighting the species-specific and broad-spectrum potential of our approach, we identified natural product inhibitors against the parasite translational machinery that have no effect on the homologous human enzyme.

microbiology↗