Internal Grant Review: A Pre-Submission Program for Early-Career Clinical and Translational Researchers
The iTHRIV Scholars Mentored Career Development Program initiated an Internal Grant Review (IGR) program in 2020 for current and recently graduated Scholars seeking funding through K and R awards from the NIH. The IGR program is designed to replicate the NIH review process and provide Scholars the opportunity to receive valuable feedback on their applications […]
Read MoreIntegrative genome-scale metabolic model of GABAergic neurons reveals metabolic signatures across the mild cognitive impairment – Alzheimer disease continuum
INTRODUCTION: Mild cognitive impairment (MCI) represents a prodromal stage of Alzheimer’s disease (AD), but the metabolic mechanisms underlying early neuronal dysfunction remain incompletely understood. GABAergic neurons, which maintain excitatory-inhibitory balance and network stability, exhibit early vulnerability during neurodegeneration, although the metabolic alterations associated with their dysfunction remain poorly characterized. METHODS: We developed a context-specific genome-scale […]
Read MoreBenchmarking biochemical networks generated by large language models
Computational models of biochemical networks provide frameworks for predicting how molecular cues guide cell decisions. These models are typically limited by the time-intensive manual curation required to extract network mechanisms from incomplete literature. Here, we test whether general-purpose large language models (LLMs) can generate accurate models of signaling and metabolic networks. We find that general-purpose […]
Read MoreIntegrating multi-omics data with network modeling to characterize Pseudomonas aeruginosa persister cell metabolism
Pseudomonas aeruginosa is a gram-negative bacterial pathogen capable of forming antimicrobial-tolerant subpopulations known as persister cells. These cells are transient phenotypic variants that can tolerate antimicrobial treatment and have been associated with chronic infections and the development of antibiotic resistance. While persister cells are classically associated with reduced metabolic activity, the characteristics of their metabolism […]
Read MoreMucin-induced metabolic reprogramming in Pseudomonas aeruginosa clinical isolates
Mucins modulate microbial metabolism, which is crucial in many human infections. It is unknown whether the metabolic alterations induced by mucin are universal or unique across varied clinical isolates of bacterial pathogens. We experimentally profiled a representative set of seven clinical Pseudomonas aeruginosa isolates in a synthetic cystic fibrosis growth medium in the presence or […]
Read MoreEnvironmental former Massilia group bacteria secrete metabolites that promote Leptospira growth
Understanding pathogen metabolism is critical for identifying key functions for drug targeting, establishing effective in vitro experimental systems, particularly for metabolically unique organisms such as Leptospira. Pathogenic Leptospira are thought to infect humans from environmental sources; however, direct isolation from environmental samples remains technically challenging and is not yet well established. Here, we report that […]
Read MoreGenome-scale metabolic modelling identifies vaginal microbiome members as potential probiotics
Probiotic supplements are marketed for diverse health benefits, yet species inclusion often lacks functional rationale. Our survey of 352 over-the-counter probiotic products available in the USA revealed 36 unique microbial species. However, there is no clear link between species inclusion and the intended health benefit. Here, to address this gap, we developed HaPaPro, a collection […]
Read MoreEnzyme-enhanced RNA isolation from biofilm-producing bacteria
RNA isolation is a critical first step for gene expression analysis; however, obtaining high-quality RNA from polysaccharide-rich or biofilm-producing microbial samples remains challenging. High polysaccharide content hinders cell lysis, decreases RNA yield, and reduces sample purity, limiting the reliability and accuracy of downstream techniques such as RNA-seq and RT-qPCR. In this study, we evaluated the […]
Read MoreMetabolic network analysis of Crohn’s disease reveals sex- and age-specific cellular phenotypes
Crohn’s disease (CD) is an inflammatory gastrointestinal disease affecting approximately 1 in 1,000 people in North America. Incidence of pediatric CD has been rising in recent decades, and this group is especially at risk of more severe disease development because of the association of CD with developmental deficits. Genome-scale metabolic models (GEMs) present an opportunity […]
Read MoreCharacterizing Spatiotemporal Expansion of Pseudomonas aeruginosa Communities in Polymer and Mucin Gel Environments
Opportunistic colonization and recurring infection by Pseudomonas aeruginosa are substantial risks to lung functionality for people with underlying respiratory diseases such as cystic fibrosis and chronic obstructive pulmonary disease. The complex metabolic and phenotypic adaptations P. aeruginosa exhibits in response to its environmental conditions make relevant in vitro models of pathogenic populations crucial for identifying […]
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