Biology subjects

Morgan, M. M.

Publications and source records attributed to Morgan, M. M..

3 recordsLinked to original sources

bioRxiv2024

MMINT: a Metabolic Model Interactive Network Tool for the exploration and comparative visualisation of metabolic networks

Genome-scale metabolic models (GEMs) are essential tools in systems and synthetic biology, enabling the mathematical simulation of metabolic pathways encoded in genomes to predict phenotypes. The complexity of GEMs, however, can often limit the interpretation and comparison of their outputs. Here, we present MMINT (Metabolic Modelling Interactive Network Tool), designed to facilitate the exploration and comparison of metabolic networks. MMINT employs GEM networks and flux solutions derived from Constraint Based Analysis (e.g. Flux Balance Analysis) to create interactive visualizations. This tool allows for seamless toggling of source and target metabolites, network decluttering, enabling exploration and comparison of flux solutions by highlighting similarities and differences between metabolic states, which enhances the identification of mechanistic drivers of phenotypes. We demonstrate MMINTs capabilities using the Pyrococcus furiosus GEM, showcasing its application in distinguishing the metabolic drivers of acetate- and ethanol-producing phenotypes. By providing an intuitive and responsive model-exploration experience, MMINT addresses the need for a tool that simplifies the interpretation of GEM outputs and supports the discovery of novel metabolic engineering strategies. MMINT is available at https://doi.org/10.6084/m9.figshare.26409328 Graphical abstractMMINT functionalities provide an intuitive and responsive model-exploration experience, enabling flux solution comparison and the identification of metabolic drivers of phenotypes O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=93 SRC="FIGDIR/small/606923v1_ufig1.gif" ALT="Figure 1"> View larger version (28K): org.highwire.dtl.DTLVardef@163d42eorg.highwire.dtl.DTLVardef@ff2922org.highwire.dtl.DTLVardef@1e5881aorg.highwire.dtl.DTLVardef@4a8bf0_HPS_FORMAT_FIGEXP M_FIG C_FIG

synthetic biology↗

bioRxiv2018

Feeding rapidly alters microbiome composition and gene transcription in the clownfish gut

BackgroundDiet is a major determinant of intestinal microbiome composition. While studies have evaluated microbiome responses to diet variation, less is understood of how the act of feeding influences the microbiome, independent of diet type. Here, we use the clownfish Premnas biaculeatus, a species reared commonly in ornamental marine aquaculture, to test how the diversity, predicted gene content, and gene transcription of the microbiome vary over a two-day diurnal period with a single daily feeding event. This study used fish fed four times daily, once daily, or every three days prior to the diurnal period, allowing us also to test how feeding frequency affected microbiome diversity. The amount of time between feedings had no affect on baseline diversity of the microbiome. In contrast, the act of feeding itself caused a significant short term change in the microbiome, with microbiome diversity, predicted gene content, and gene transcription varying significantly between time points immediately before and 1.5 hours post feeding. Variation was driven by abundance shifts involving exact sequence variants (ESVs), with one ESV identified as Photobacterium sp. increasing from <0.5% of sequences immediately pre-feeding to 34% at 1.5 hours post-feeding. Other ESVs from a range of microbial groups also increased dramatically after feeding, with the majority also detected in the food. One ESV identified as Clostridium perfringens represented up to 55% of sequences but did not vary significantly over the diurnal period and was not detected in the food. Post-feeding samples were enriched in transcripts and predicted genes for social interactions, cell motility, and coping with foreign DNA, whereas time points farther from feeding were enriched in genes of diverse catabolic and biosynthetic functions. These results confirm feeding as a significant destabilizing force in clownfish intestinal microbiomes, likely due to both input of cells attached to food and stimulation of resident microbes. Microbes such as Photobacterium may episodically transition from environmental reservoirs to growth in the gut, likely in association with food particles. This transition may be facilitated by functions for navigating a new environment and interacting with neighboring microbes and host cells. Other taxa, such as Clostridium, are comparatively stable intestinal members and less likely to be affected by passing food. Conclusions about microbiome ecology may therefore differ based on when samples were collected relative to the last feeding.\n\nImportanceDespite extensive study of intestinal microbiome diversity and the role of diet type in structuring gut microbial communities, we know very little about short-term changes in the intestinal microbiome as a result of feeding alone. Sampling microbiomes over a feeding cycle will allow us to differentiate opportunistic, feeding-responsive microbes from resident, potentially commensal members of the gut community. Also, since feeding has the potential to alter microbiome structure, sampling at different points relative to the last feeding event will likely yield different conclusions about microbiome composition and function. This variation should be addressed in comparative microbiome studies. Our study contributes to knowledge of short-term changes in the gut microbiome associated with feeding events.

microbiology↗

bioRxiv2018

Acute Hyperalgesia and Delayed Dry Eye After Corneal Abrasion Injury

Corneal nerves mediate pain from the ocular surface, lacrimation, and blinking, all of which protect corneal surface homeostasis and help preserve vision. Corneal nerve density correlates with neuropathic pain states and is used as an assessment of small fiber neuropathies. Because pain, lacrimation and blinking are rarely assessed at the same time, it is not known if their regulatory mechanisms have similar temporal dynamics after acute corneal injury. We examined changes in corneal nerve density, evoked and spontaneous pain, and ocular homeostasis in Sprague-Dawley male rats after a superficial epithelial injury with heptanol that acutely abolished nerve endings within the central cornea. Despite a profound loss of epithelial nerve endings, pain was transiently enhanced after abrasion injury, while basal tear production was normal. We found no relationship between epithelial nerve density and pain or homeostatic responses. Axotomy following corneal abrasion increased expression of both ATF3 (a nerve injury marker) and CGRP (a nociceptive peptide) in trigeminal ganglia 24 hours after injury. These molecular changes were absent on the contralateral side, despite reductions in corneal epithelial nerve density in the uninjured eye. ATF3 and CGRP levels in trigeminal ganglion were normal at one week post-injury when pain responses were normal. In contrast, CGRP was upregulated in peripheral corneal endings one week after injury, when dry eye symptoms emerged. Our results demonstrate dynamic trafficking of CGRP within trigeminal sensory nerves, with elevations in the ganglion correlated with pain behaviors and elevations in peripheral endings correlated with dry eye symptoms.

neuroscience↗