Biology subjects

Shamoon, N. M.

Publications and source records attributed to Shamoon, N. M..

4 recordsLinked to original sources

bioRxiv2025

An optimized protocol for Candida albicans infection in Schmidtea mediterranea to study fungal pathogenesis and host defense

Candida albicans is a common opportunistic fungal pathogen that asymptomatically colonizes most humans. Although typically a benign commensal, dysbiosis caused by antibiotic use, immune dysfunction, or epithelial barrier disruption can trigger fungal overgrowth and infection, ranging from superficial mucosal disease to life-threatening systemic candidiasis. New preclinical infection models are needed to dissect C. albicans pathogenesis in vivo across distinct stages of infection and with different measurable host outcomes. We previously established the planarian Schmidtea mediterranea as an invertebrate host for studying host-pathogen interactions during C. albicans infection. S. mediterranea relies entirely on conserved innate immune mechanisms capable of overcoming infection with pathogenic microorganisms, including bacteria and fungi. Planarians remarkable regenerative capacity and accessible stem cell populations make this organism a tractable model to analyze early immune responses, tissue repair, and pathogen clearance in vivo. This model supports simultaneous analysis of fungal virulence and host transcriptional responses, providing valuable insights into infection dynamics. Here, we present an updated protocol with detailed modifications, standardized procedures, and optimized steps for infecting S. mediterranea with C. albicans, designed to enhance reproducibility and enable systematic studies of fungal pathogenesis and host defense. SUMMARYWe present an optimized and detailed protocol for using the planarian Schmidtea mediterranea as a model system to study host-pathogen interactions during fungal infection. This method builds on our previous procedure for infecting planarians with the human fungal pathogen Candida albicans, providing detailed guidance to enhance reproducibility and experimental consistency. The system enables comprehensive, parallel analysis of both host and pathogen responses throughout infection - from initial colonization and disease progression to diverse host outcomes, including clearance or mortality.

microbiology↗

bioRxiv2023

Sequence-ensemble-function relationships for disordered proteins in live cells

Despite lacking a stable three-dimensional structure, intrinsically disordered protein regions (IDRs) are ubiquitous across all kingdoms of life and play essential cellular roles. While rational design of folded proteins has seen substantial recent progress, our ability to design IDRs remains limited. Here, we present GOOSE, a comprehensive computational framework for the rational design of IDRs. GOOSEs versatility and throughput enable us to test thousands of IDR sequences, revealing distinct sequence-ensemble-function relationships. By using GOOSE to rapidly explore these relationships, we design IDRs that can alter their ensembles in response to cell volume changes, create scaffolds for the self-assembly of specific clients, and protect cells from desiccation. Taken together, this work highlights how sequence-function relationships are encoded in IDRs and provides a powerful tool for further exploration.

biophysics↗

bioRxiv2021

Hidden structure in disordered proteins is adaptive to intracellular changes

Intrinsically disordered proteins and protein regions (IDPs) are essential to cellular function in all proteomes. Unlike folded proteins, IDPs exist in an ensemble of rapidly interchanging conformations. IDP sequences encode interactions that create structural biases within the ensemble. Such structural biases determine the three-dimensional shape of IDP ensembles and can affect their activity. However, the plasticity and sensitivity of IDP ensembles means structural biases, often measured in vitro, may differ in the dynamic and heterogeneous intracellular environment. Here we reveal that structural biases found in vitro in well-studied IDPs persist inside human-derived cells. We further show that a subset of IDPs are able to sense changes in cellular physical-chemical composition and modulate their ensemble in response. We propose that IDP ensembles can evolve to sense and respond to intracellular physicochemical changes, or to resist them. This property can be leveraged for biological function, be the underlying cause of IDP-driven pathology, or be leveraged for the design of disorder-based biosensors and actuators.

biophysics↗

bioRxiv2020

Probing the Hidden Sensitivity of Intrinsically Disordered Proteins to their Chemical Environment

Intrinsically disordered proteins and protein-regions (IDRs) make up roughly 30% of the human proteome and play vital roles in a wide variety of biological processes. Given a lack of persistent tertiary structure, all of the residues in an IDR are, to some extent, solvent exposed. This extensive surface area, coupled with the absence of strong intramolecular contacts, makes IDRs inherently sensitive to their chemical environment. Despite this sensitivity, our understanding of how IDR structural ensembles are influenced by changes in their chemical environment is limited. This is particularly relevant given a growing body of evidence showing that IDR function is linked to the underlying structural ensemble. We develop and use a combined experimental, computational, and analytical framework for high-throughput characterization of IDR sensitivity we call solution space scanning. Our framework reveals that IDRs show sequence-dependent sensitivity to solution chemistry, with complex behavior that can be interpreted through relatively simple polymer models. Our results imply that solution-responsive IDRs are ubiquitous and can provide an additional layer of biological regulation.

biophysics↗