Biology subjects

Oviedo, N. J.

Publications and source records attributed to Oviedo, N. J..

5 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↗

bioRxiv2024

Planarians Develop Radiotolerance to Recurrent Ionizing Radiation Exposure

Exposure to ionizing radiation can induce DNA fragmentation, leading to double-strand breaks, the most toxic form of DNA damage. Some organisms have developed mechanisms to overcome the adverse effects of ionizing radiation by enhancing DNA protection and repair. However, the underlying mechanisms driving radiation resistance to maintain genomic integrity and function remain poorly understood. Here, we provide evidence for the development of radiotolerance in the flatworm planarian Schmidtea mediterranea. We implemented a strategy to select animals capable of overcoming repeated rounds of ionizing radiation exposure. We demonstrate that planarians initially exposed to higher amounts of sub-lethal radiation can adapt, gaining the ability to recover reproductive capabilities faster than animals initially exposed to lower amounts of sub-lethal radiation. Our findings show that DNA integrity is reestablished in about one week after five cycles of sub-lethal ionizing radiation exposure. Planarian stem cells, known as neoblasts, can repair repeated DNA double-strand breaks by activating Rad51-mediated homologous recombination. The expression of the neoblast marker smedpiwi-1 and the mitotic activity reach levels similar to unirradiated animals between two and three weeks post-radiation. We describe that planarians develop radiotolerance through recurrent ionizing radiation exposure over several years and survive without apparent functional or morphological defects for an undetermined time.

developmental biology↗

bioRxiv2024

The DNA Methyltransferase DMAP1 is Required for Tissue Maintenance and Planarian Regeneration

The precise regulation of transcription is required for embryonic development, adult tissue turnover, and regeneration. Epigenetic modifications play a crucial role in orchestrating and regulating the transcription of genes. These modifications are important in the transition of pluripotent stem cells and their progeny. Methylation, a key epigenetic modification, influences gene expression through changes in histone tails and direct DNA methylation. Work in different organisms has shown that the DNA methyltransferase-1-associated protein (DMAP1) may associate with other molecules to repress transcription through DNA methylation. Thus, DMAP1 is a versatile protein implicated in a myriad of events, including pluripotency maintenance, DNA damage repair, and tumor suppression. While DMAP1 has been extensively studied in vitro, its complex regulation in the context of the adult organism remains unclear. To gain insights into the possible roles of DMAP1 at the organismal level, we used planarian flatworms that possess remarkable regenerative capabilities driven by pluripotent stem cells called neoblast. Our findings demonstrate the evolutionary conservation of DMAP1 in the planarian Schmidtea mediterranea. Functional disruption of DMAP1 through RNA interference revealed its critical role in tissue maintenance, neoblast differentiation, and regeneration in S. mediterranea. Moreover, our analysis unveiled a novel function for DMAP1 in regulating cell death in response to DNA damage and influencing the expression of axial polarity markers. Our findings provide a simplified paradigm for studying DMAP1s epigenetic regulation in adult tissues. HighlightsO_LIEpigenetic regulation through DMAP1 is evolutionarily conserved in Schmidtea mediterranea and is crucial for tissue maintenance and regeneration. C_LIO_LINeoblast differentiation into epithelial, muscle, digestive, and neural fate requires DMAP1. C_LIO_LIDMAP1 regulates DNA stability and cell death during adult cell turnover. C_LIO_LIDMAP1 regulates the spatial expression of axial polarity markers in S. mediterranea. C_LI

developmental biology↗

bioRxiv2021

Restoration of DNA Integrity and Cell Cycle by Electric Stimulation in Planarian Tissues Damaged by Ionizing Radiation

Exposure to high levels of ionizing {gamma}-radiation leads to irreversible DNA damage and cell death. Here, we establish that exogenous application of electric stimulation enables cellular plasticity to reestablish stem cell activity in tissues damaged by ionizing radiation. We show that sub-threshold direct current stimulation (DCS) rapidly restores pluripotent stem cell populations previously eliminated by lethally {gamma}-irradiated tissues of the planarian flatworm Schmidtea mediterranea. Our findings reveal that DCS enhances DNA repair, transcriptional activity, and cell cycle entry in post-mitotic cells. These responses involve rapid increases in cytosolic [Ca2+] through the activation of L-type Cav channels and intracellular Ca2+ stores leading to the activation of immediate early genes and ectopic expression of stem cell markers in postmitotic cells. Overall, we show the potential of electric current stimulation to reverse damaging effects of high dose {gamma}-radiation in adult tissues. Furthermore, our results provide mechanistic insights describing how electric stimulation effectively translates into molecular responses capable of regulating fundamental cellular functions without the need for genetic or pharmacological intervention.

developmental biology↗

bioRxiv2020

Epithelial infection with Candida albicans elicits a multi-system response in planarians

Candida albicans is one of the most common fungal pathogens of humans. Prior work introduced the planarian Schmidtea mediterranea as a new model system to study the host response to fungal infection at the organismal level. In the current study, we analyzed host-pathogen changes that occurred in situ during early infection with C. albicans. We found that the transcription factor Bcr1 and its downstream adhesin Als3 are required for C. albicans to adhere to and colonize the planarian epithelial surface, and that adherence of C. albicans triggers a multi-system host response that is mediated by the Dectin signaling pathway. This infection response is characterized by two peaks of stem cell divisions and transcriptional changes in differentiated tissues including the nervous and the excretory systems. This response bears some resemblance to a wound-like response to physical injury; however, it takes place without visible tissue damage and it engages a distinct set of progenitor cells. Overall, we identified two C. albicans proteins that mediate epithelial infection of planarians and a comprehensive host response facilitated by diverse tissues to effectively clear the infection.

developmental biology↗