A5005365379- Insect and Arachnid Ecology and Behavior
- Insect symbiosis and bacterial influences
- Insect and Pesticide Research
- Receptor Mechanisms and Signaling
- Plant and animal studies
- Nicotinic Acetylcholine Receptors Study
- Chemical Synthesis and Analysis
- Crystallography and molecular interactions
- Neuropeptides and Animal Physiology
- RNA and protein synthesis mechanisms
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Mass Spectrometry Techniques and Applications
- Entomopathogenic Microorganisms in Pest Control
- Axial and Atropisomeric Chirality Synthesis
- Antimicrobial Peptides and Activities
- Analytical Chemistry and Chromatography
- Cholinesterase and Neurodegenerative Diseases
- Synthesis and Biological Evaluation
- Lipid Membrane Structure and Behavior
- Chemical Reaction Mechanisms
- Microbial Natural Products and Biosynthesis
- Ion channel regulation and function
- Molecular spectroscopy and chirality
Scripps College
2017-2023
Harvard University
2015-2021
Claremont Colleges
2017
Claremont McKenna College
2017
Pitzer College
2017
California Institute of Technology
2010-2014
Bowdoin College
2006
Colby College
2006
University of Tulsa
2006
Significance Bacteria use small molecules to mediate their relationships with nearby microbes, and these represent both a promising source of therapeutic agents model system for the evolution dissemination molecular diversity. This study deals one such molecule, selvamicin, which is produced by ant-associated bacteria. These bacteria protect ants’ nests against fungal pathogens. Selvamicin an atypical member clinically important class antifungal agents, it appears have better properties...
Small molecules produced by Actinobacteria have played a prominent role in both drug discovery and organic chemistry. As part of larger study the actinobacterial symbionts fungus-growing ants, we discovered small family three previously unreported piperazic acid-containing cyclic depsipeptides, gerumycins A-C. The are slightly smaller versions dentigerumycin, depsipeptide that selectively inhibits common fungal pathogen, Escovopsis. We had identified this molecule from Pseudonocardia...
Bacterial symbionts of fungus-growing ants occupy a highly specialized ecological niche and face the constant existential threat displacement by another strain ant-adapted bacteria. As part systematic study small molecules underlying this fraternal competition, we discovered an analog antitumor agent rebeccamycin, member increasingly important indolocarbazole family. While several gene clusters consistent with molecule's newly reported modification had previously been identified in...
Fungus-growing ants engage in a multilateral symbiosis: they cultivate fungal garden as their primary food source and host symbiotic actinobacteria (Pseudonocardia spp.) that provide chemical defenses. The bacterial symbionts produce small specialized metabolites protect the from specific pathogens (Escovopsis spp.), return, are fed by ant hosts. Multiple studies on molecules underlying this system have led to discovery of large number structurally diverse antifungal molecules, but somewhat...
G protein-coupled receptors (GPCRs) contain a number of conserved proline residues in their transmembrane helices, and it is generally assumed these play important functional and/or structural roles. Here we use unnatural amino acid mutagenesis, employing α-hydroxy acids analogues, to examine the roles five helices D2 dopamine receptor. The well-known tendency disrupt helical structure at all sites, while find no evidence for role backbone amide cis–trans isomerization, another feature...
Fungus-growing ants and their microbial symbionts have emerged as a model system for understanding antibiotic deployment in an ecological context. Here we establish that bacterial of the ant Trachymyrmex septentrionalis antagonize most likely competitors, other strains ant-associated bacteria, using thiopeptide GE37468. Genomic analysis suggests these acquired GE37468 gene cluster from soil bacteria. This antibiotic, with known activity against human pathogens, was previously identified...
The <i>α</i>7 nicotinic acetylcholine receptor shows broad pharmacology, complicating the development of subtype-specific agonists. Here we use unnatural amino acid mutagenesis to characterize binding by smoking cessation drug varenicline (Chantix; Pfizer, Groton, CT), an <i>α</i>4<i>β</i>2-targeted agonist that full efficacy and modest potency at receptor. We find unlike its target receptor, does not form a cation-<i>π</i> interaction with TrpB, further supporting unique mode for cationic...
Symbiotic Actinobacteria help fungus-growing ants suppress fungal pathogens through the production of antifungal compounds. Trachymyrmex southwest desert United States inhabit a unique niche far from tropical rainforests in which most ant species are found. These may not encounter specialist pathogen Escovopsis known to threaten colonies other ants. It is unknown whether associated with these antagonize contaminant fungi and, if so, what chemical basis such antagonism is. We find that...
Fungus-growing ants are defended by antibiotic-producing bacterial symbionts in the genus Pseudonocardia. Nutrients provisioned support these but also invite colonization and competition from other bacteria. As an arena for chemically mediated competition, this niche offers a window into ecological antibiotic function with well-defined competing organisms. From multiple colonies of desert specialist ant Trachymyrmex smithi, we isolated Amycolatopsis bacteria that inhibit growth...
Abstract The geographic and phylogenetic scale of ecologically relevant microbial diversity is still poorly understood. Using a model mutualism, fungus-growing ants their defensive bacterial associate Pseudonocardia , we analyzed genetic biosynthetic potential in 46 strains isolated from ant colonies 20km transect near Barro Colorado Island Panama. Despite an average pairwise core genome similarity greater than 99%, population genomic analysis revealed several distinct populations matching...
A series of chiral imidazole-4,5-dicarboxylic acid derivatives was prepared in order to test the significance that stereochemistry and substitution have on preferred intermolecular associations compounds solution solid state. Solution 1H NMR spectroscopy provided evidence for racemic by enantiomeric imidazole-4,5-dicarboxamides (I45DCs) but not imidazole-4-carboxylic ester-5-carboxamides (I45EAs). Melting point phase diagrams illustrate dissymmetrically disubstituted preferably form It is...
Fungus-growing ants and their bacterial symbionts have emerged as a model animal-microbe symbiosis an ideal system for understanding antibiotic deployment in ecological context. We found that <i>Pseudonocardia</i> of the ant <i>Trachymyrmex septentrionalis</i> strong activity against most likely competitors: other strains ant-associated bacteria. Activity-guided fractionation revealed defensive molecule produced by these bacteria to be thiopeptide GE37468. Here we...
Abstract Review: [70 refs.
Fungus-growing ants and their bacterial symbionts have emerged as a model animal-microbe symbiosis an ideal system for understanding antibiotic deployment in ecological context. We found that Pseudonocardia of the ant Trachymyrmex septentrionalis strong activity against most likely competitors: other strains ant-associated bacteria. Activity-guided fractionation revealed defensive molecule produced by these bacteria to be thiopeptide GE37468. Here we assign role – host-associated niche...
Fungus-growing ants are defended by antibiotic-producing bacterial symbionts in the genus Pseudonocardia. Nutrients provisioned support these but also invite colonization and competition from other bacteria. As an arena for chemically-mediated competition, this niche offers a window into ecological antibiotic function with well-defined competing organisms. From multiple colonies of desert specialist ant Trachymyrmex smithi, we isolated Amycolatopsis bacteria that inhibit growth...