Search

Since the first studies looking into how plant specialized metabolites provide defense from herbivory, the field of chemical ecology has explored how organisms interact within their environment, and how these interactions structure the ecosystem. Over the last century, we have come to understand a lot about chemical signaling in plants and animals, but our understanding of bacterial chemical signaling is still in its infancy. This is partially because most of the focus has been placed on understanding bacteria potential for drug development as opposed to understanding their ecological roles. This thesis consists of five chapters and explores the interplay between bacterial specialized metabolites in marine sediments, their producers, and their ecological roles, by focusing on the model marine bacterial genus Salinispora. What follows are three research chapters preceded by an introduction to chemical ecology. The introduction focuses on our current understanding of marine bacterial chemical ecology, followed by a brief description of cutting edge mass spectrometry techniques that are now being exploited to further our understanding of the chemical landscape in the environment.Chapter 2 summarizes a study concerning the identification of specialized metabolites in situ and the correlation between these metabolites and their potential producers. Heterotrophic marine sediment bacteria are prolific producers of natural products, but surprisingly little is known about the compounds they produce in the environment and their effects on co-occurring microbes. Using mass spectrometry and molecular networking, characterization of the sediment metabolome was undertaken from Belizean reef habitats. Dereplication results revealed numerous compounds could be detected directly from the sediments including synthetic, sponge, algal, and bacterial metabolites. Interestingly, one of these compounds, the cytotoxin staurosporine, was further quantified and found to occur in the sediments at abundances higher than those established to inhibit protein kinases as well as marine organisms. A 16S rRNA community analysis as well as culturing helped correlate the production of staurosporine to the obligate marine actinomycete species Salinispora arenicola. These results indicate that microbial organisms are likely capable of producing cytotoxins in situ at appreciable quantities that likely impact the community structure of the sediment biome.Since the cytotoxin staurosporine, which is produced by Salinispora, was found to be abundant in the sediments, chapter 3 explored the potential for Salinispora to deter predatory eukaryotic organisms. S. arenicola and S. tropica co-occur in the Caribbean and share greater than 99% 16s rRNA. A recent sequencing effort revealed that each species maintains a unique set BGCs, with S. arenicola containing the BGC to produce staurosporine and S. tropica the BGCs to produce lomaiviticins, and salinosporamides. Numerous assays were developed to assess the ability of Salinispora spp. to deter feeding by the bacterivore C. elegans. Results indicated that S. tropica strains can produce a suite of lomaiviticins that deter C. elegans feeding at ecologically relevant concentrations, however; S. arenicola strains do not produce deterrent allelochemicals at ecologically relevant concentrations. Follow up studies using more ecologically relevant organisms indicated that this trend was still prevalent when tested against the marine polychaete Ophryotrocha n sp. as well as marine nematodes. In chapter 3, I saw that Salinispora spp. exhibit different chemodeterrent strategies against bacterivorous eukaryotes. However, this study relied on constitutively produced specialized metabolites, even though there are numerous examples where microbial specialized metabolites can be induced in response to biotic stressors in the environment. To address this chapter 4 focuses on a high throughput method I developed to look at induction of specialized metabolites in co-cultures containing Salinispora and marine bacterial challengers. Results indicate that induction is prevalent in cocultures using all Salinispora strains tested. The induced mass features were also unique to cocultures indicating that induction is strain and not species specific. Efforts to identify compounds that were induced in cocultures resulted in the identification of a suite of desferrioxamines that were upregulated in some Salinispora strains in response to specific Streptomyces challengers, indicating that some Salinispora strains can modulate the production of iron scavenging specialized metabolites in response to stressors.Chapter 5 provides conclusions related to the thesis and how it fits into the broader context of marine microbial chemical ecology.

The incidence of differentiated thyroid carcinoma (DTC) has increased in recent decades with early stage, low risk papillary thyroid cancer (PTC) being detected and diagnosed. As a result, the psychological, financial, and clinical ramifications of overdiagnosis and excessively aggressive therapy are being increasingly recognized with many authorities calling for a re-evaluation of the traditional “one size fits all” management approaches. To address these critical issues, most thyroid cancer guidelines endorse a more risk adapted management strategy where the intensity of therapy and follow up is matched to the anticipated risk of recurrence and death from DTC for each patient. This “less is more” strategy provides for a minimalistic management approach for properly selected patients with low-risk DTC. This has re-kindled the long-standing debate regarding the routine use of radioactive iodine therapy (RIT) in DTC. Although recent guidelines have moved toward a more selective use of RIT, particular in patients with low-intermediate risk DTC, the proper selection of patients, the expected benefit, and the potential risks continue to be a source of ongoing controversy and debate. In this manuscript, we will review the wide range of clinical, imaging, medical team, and patient factors that must be considered when evaluating individual patients for RIT. Through a review of the current literature evaluating the potential benefits and risks of RIT, we will present a risk adapted approach to proper patient selection for RIT which emphasizes peri-operative risk stratification as the primary tool that clinicians should use to guide initial RIT management recommendations.