Glen Gerald DSouza

My research program focusses on microbiomes that process glycans (also termed as polysaccharides), which are the dominant stocks of carbon on the planet. The degradation of glycans by members of microbiomes has ramifications for human health as well as propagation of biogeochemical cycles crucial for planetary health. While existing research has either adopted a top-down metagenomic approach or centered on individual species' physiology, my strategy integrates these perspectives through the lens of microscale microbial ecology. 

My group utilizes microfluidic growth experiments coupled to quantitative single cell imaging. We employ image analysis pipelines that enable machine learning guided analyses of growth and behavior of individual cells, and intercellular interaction networks at the microscale within complex microbiomes. We combine single-cell measurements, with physiological assays, experimental evolution, high-throughput genetic screens, and transcriptomics to understand the operation, composition and function of microbial communities. 

My group leverages large-scale metagenomic datasets from human and environmental studies to inform the development of microbiome properties that are key at the microscale and quantify these properties at the level of single-cells. Such a multi-scale approach helps determine of how microscale dynamics influence the ecology and evolution of intercellular networks within microbiomes.

Currently, we have three major directions of interest:

Theme 1: Mechanisms of intercellular interaction network emergence and consequences on functional composition of microbial communities.

Here, we investigate how nutrients in the environment determines spatial organization and intercellular interactions within microbiomes. Specifically, we investigate which cells interact and how they interact and influence microbiome composition and function. We test a number of predictions at the microscale (using microfluidics coupled to automated image analysis) along with unravelling mechanisms of glycan breakdown and cross-feeding by members of microbiomes (using transcriptomics and high-throughput genetic screens) and quantify nutrient flow between different microbiome members (Nanoscale Secondary Ion Mas Spectroscopy). 

Theme 2: Intercellular interactions and response of microbiomes to environmental perturbations

Here, we focus on the role of microscale interaction networks in determining the ability of microbiome members to survive environmental perturbations that affect community survival. We subject microbiomes to three specific perturbations that communities frequently experience in nature. First, changes in the type of glycan that microbiomes encounter in their environment, for instance during algal blooms in marine microbiomes or dietary shifts in the host nutrient composition of the environment in host-associated microbiomes. Second, presence of antimicrobial compounds, that can inhibit bacterial growth, appear in the environment, for instance when marine algae secrete growth inhibitory metabolites or medicinal interventions introduce antibiotics in host associated microbiomes. Third, we focus on increasing temperature, a scenario that environmental communities are increasingly facing in natural environments. We test predictions by quantifying the growth of communities in fluctuating environments and complement these analyses with investigations of functional performance, for instance with measurements of carbon break down capabilities before and after environmental change.

Theme 3: Evolution of intercellular interaction networks in microbiomes to improve functions

The microscale interaction network is a key determinant of how microbiome operate. Here, we investigate how the topology of microscale interaction networks shape the evolutionary trajectories of microbiomes and ask if we can design topologies that facilitate the development of microbiomes to achieve specific functions like carbon remineralization or sequestration. We test predictions by experimentally evolving microbiomes with distinct interaction networks and unravel the molecular mechanisms that underly adaptation using genomics (transcriptomics and resequencing). In parallel, we study ecological dynamics at the microscale of microbiomes consisting of members, where we have genetically altered the propensity to engage in interactions the removal or altered expression of genes.