Biology subjects

Raman, A. S.

Publications and source records attributed to Raman, A. S..

4 recordsLinked to original sources

bioRxiv2026

Physiological architecture and evolutionary origins of cellular adaptability

The capacity to adapt to complex environments ( adaptability) is a defining property of cells. Yet, its relationship across single-cell physiology, population-level responses, and evolutionary timescales remains unclear. We performed single-cell transcriptional profiling of budding yeast across 20 complex environments before and after long-term selection for increased osmotolerance. In ancestral populations, transcriptional responses organized into a reproducible hierarchy where adaptation to certain cues took precedence over others. This hierarchy mechanistically originated within individual cells through contingent regulation of translation initiation. Evolution for >3,000 generations under osmotic stress increased osmotolerance while reordering this hierarchy, selectively deprioritizing osmotic stress as an organizing axis of adaptation. The derived strain exhibited impaired integration of stress responses, defective translational coordination, and reduced fitness outside the selected condition. Together, these findings illustrate that cellular adaptability is an evolved architecture whose form is set by the history of selection. One Sentence SummaryCells adapt to complex environments via a prioritization hierarchy; this hierarchy is shaped by the frequency and magnitude of environmental fluctuations in their evolutionary history.

cell biology↗

bioRxiv2026

Distinct trajectories of urbanization shape the human gut microbiome across South Asia

Human gut microbiomes respond to lifestyle transitions, yet the extent to which these responses are conserved across spatio-cultural contexts remains undercharacterized. We present the South Asian MicroBiome ARray (SAMBAR), a population-scale 16S gut microbiome study of 575 adults from ten geographically and socio-culturally diverse South Asian communities. Each community was sampled in ancestral villages and urban centers, enabling controlled comparisons of geography and lifestyle. Relative to global cohorts, SAMBAR microbiomes occupy a distinct compositional space with stronger correlation to geography and community membership than lifestyle. Although urbanization is consistently associated with increased abundance of disease-linked taxa, microbiome responses to lifestyle transitions are largely community-driven, including the acquisition of wheat- and dairying-associated microbial modules in some communities that may facilitate non-genetic adaptation to lactase non-persistence. Microbiome responses to urbanization are heterogeneous even at regional scales, reflecting local culture and geography and underscoring the need for community-specific investigations of health impacts.

microbiology↗

bioRxiv2026

Post-COVID impairment of memory T cell responses to community-acquired pathogens can be rectified by activating cellular metabolism

Infection rates involving bacterial and viral pathogens have increased precipitously after the COVID-19 pandemic. While it has been speculated that higher infection rates resulted from increased hospitalizations throughout the pandemic or greater use of antibiotics, precisely why rates remain high today has remained unexplained. Mitochondrial dysfunction is known to occur post-COVID and may disrupt immune responses. Within T cells, SARS-CoV-2 infection is linked to low mitochondrial membrane potential, increased mitochondrial apoptosis, and decreased mitochondrial respiration, which together impact cellular activation and function beyond the acute phase of illness. Here, we demonstrate that decreased mitochondrial function in antigen-specific T cells post-COVID may contribute to higher infection susceptibility by metabolically immobilizing T cell memory responses. Using donor-matched peripheral blood samples from 31 COVID-naive individuals who subsequently contracted COVID-19, we tracked how influenza A (IAV), Staphylococcus aureus (SA), and Varicella-zoster virus (VZV) T cell responses were impacted by COVID-19 infection. We found that gene expression linked to T cell activation decreased but mitochondrial redox pathways increased in CD4 memory T cells post-COVID. However, mitochondrial flux and reactive oxygen species production were limited in a plurality of post-COVID memory T cells after stimulation with IAV, SA, and VZV. Furthermore, we found a disordered relationship between memory T cell mobilization of glycolysis, fatty acid metabolism, and oxidative phosphorylation pathways post-COVID which resulted in diminished use of catabolic pathways including glycolysis and fatty acid oxidation in antigen-specific T cells. Modulation of mitochondrial function with metformin and ubiquinol partially rescued the post-COVID decline in T cell catabolism. Collectively, these findings indicate that COVID-19 infection may have lasting effects on inhibiting T cell memory responses to commonly encountered community-acquired pathogens which can be corrected with commonly available medications. This has significant implications for the clinical care of immunologically vulnerable populations in the post-pandemic era.

immunology↗

bioRxiv2023

Learning the functional landscape of microbial communities

Microbial consortia exhibit complex functional properties in contexts ranging from soils to bioreactors to human hosts. Understanding how community composition determines emergent function is a major goal of microbial ecology. Here we address this challenge using the concept of community-function landscapes - analogs to fitness landscapes - that capture how changes in community composition alter collective function. Using datasets that represent a broad set of community functions, from production/degradation of specific compounds to biomass generation, we show that statistically-inferred landscapes quantitatively predict community functions from knowledge of strain presence or absence. Crucially, community-function landscapes allow prediction without explicit knowledge of abundance dynamics or interactions between species, and can be accurately trained using measurements from a small subset of all possible community compositions. The success of our approach arises from the fact that empirical community-function landscapes are typically not rugged, meaning that they largely lack high-order epistatic contributions that would be difficult to fit with limited data. Finally, we show this observation is generic across many ecological models, suggesting community-function landscapes can be applied broadly across many contexts. Our results open the door to the rational design of consortia without detailed knowledge of abundance dynamics or interactions.

ecology↗