UC Berkeley

Microbial communities inhabit nearly every ecosystem on Earth and have large effects on their environment, including impacts on crucial processes like host health and global nutrient cycling. Understanding the biotic and abiotic factors that influence the structure and function of these communities is crucial for predicting their continued impacts on a changing planet. A challenge to studying microbial communities in detail is their complexity. These communities often contain hundreds to thousands of species that are growing and metabolizing different compounds, making it challenging to deduce how individual species impact one another or how particular nutrients may affect the functioning of a community.

The model nutrient approach poses a solution to the challenges of studying microbial community interactions. Corrinoids, the vitamin B12 family of enzyme cofactors, are synthesized by bacteria and archaea and required by organisms in all domains of life for different metabolic processes. Genomic analysis and microbial co-culture studies have shown that these nutrients are shared among microbes. Further, bacteria have preferences for specific corrinoids that affect their growth and may lead to corrinoids impacting community structure. For these reasons, the corrinoid model is ideal for studying interactions among bacteria across multiple scales, spanning molecules to communities.

In Chapter 1, I present a review of corrinoid biology across scales of increasing complexity, summarizing knowledge recovered over the last century that informs the model nutrient approach. At the molecular scale, corrinoid biology spans enzymes, transporters, regulatory riboswitches, and an elaborate biosynthesis pathway. These components give rise to corrinoid diversity and preferences for different corrinoids observed at the organismal scale. At the organismal scale, defining the categories of “producer,” “dependent,” “independent,” and “provider” is the genomic and experimental basis for characterizing and predicting interactions. These definitions contribute to the community scale, where nutrient sharing can be studied in co-cultures of producers and dependents, and different corrinoids have been shown to impact community structure. These scales come together to enable the study of microbial interactions and continued research will enable expansion into new scales.

In Chapter 2, I applied the model nutrient approach at the organismal scale through the isolation of bacteria from a soil environment and characterization of producers, dependents, and independents. The results revealed a bias for B12 among isolates; tested producers all synthesized B12 and dependents preferred it over other corrinoids. Further, a set of producers were classified as providers after corrinoid was detected in culture supernatants. These observations, combined, led to the hypothesis that these isolates may interact via corrinoid sharing in their native environment. As part of this research, I evaluated the phylogenetic dispersion of producer, dependent, and independent traits among sequenced bacteria and found that corrinoid metabolism can be predicted from taxonomy for around half of the genera studied.

In Chapter 3, I applied the model nutrient approach at the community scale with a focus on co-cultures and three-species consortia. Comparison of the monoculture growth of corrinoid-dependent isolates to their growth in co-cultures showed that the outcome of competition is predictable based on corrinoid preferences when preferences are sufficiently distinct. As part of this work, I tested interactions between producers and dependents to evaluate whether these isolates interacted by sharing corrinoids, a hypothesis generated in Chapter 2. While producers supported dependent growth by sharing B12, interactions in co-culture were not easily predictable based on monoculture growth of dependents provided with producer supernatant. Finally, tests in tri-cultures showed that dependents compete for the corrinoids made available by producers. Despite emergent properties arising, results were consistent with corrinoid-based interactions being the predominant interaction in these consortia. Together, Chapters 2 and 3 illustrate the applicability of the model nutrient approach in individual bacteria and small communities and establish a system in which interactions can be further tested.

In Chapter 4, I pivot to a diversity, equity, inclusion, and belonging project focused on the qualifying exam experience of graduate students. The Inclusive Excellence in Quals Prep (IEQP) pilot program focused on increasing support for students as they go through their qualifying exam by creating a support network and providing structure during the preparation process. The program’s effectiveness was evaluated through a series of surveys presented here. IEQP was demonstrated to be effective in its first year, with peer mentorship identified as a key component.