A5018168734- Mitochondrial Function and Pathology
- Microbial Metabolic Engineering and Bioproduction
- Photosynthetic Processes and Mechanisms
- Bacterial Genetics and Biotechnology
- Evolution and Genetic Dynamics
- Genomics and Phylogenetic Studies
- Cancer, Hypoxia, and Metabolism
- Gene Regulatory Network Analysis
- Machine Learning in Bioinformatics
- ATP Synthase and ATPases Research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Microbial Fuel Cells and Bioremediation
- RNA and protein synthesis mechanisms
- Clusterin in disease pathology
- COVID-19 Clinical Research Studies
- Plant Stress Responses and Tolerance
- Metabolism, Diabetes, and Cancer
- Insect and Pesticide Research
- Cancer-related Molecular Pathways
- Biomedical Ethics and Regulation
- CRISPR and Genetic Engineering
- Biofuel production and bioconversion
- Gene expression and cancer classification
- Toxin Mechanisms and Immunotoxins
- CAR-T cell therapy research
University of California, San Diego
2016-2025
La Jolla Bioengineering Institute
2023-2024
VA San Diego Healthcare System
2021-2022
University of Delaware
2014
Abstract It has proved challenging to quantitatively relate the proteome transcriptome on a per-gene basis. Recent advances in data analytics have enabled biologically meaningful modularization of bacterial transcriptome. We thus investigate whether matched datasets transcriptomes and proteomes from bacteria under diverse conditions can be modularized same way reveal novel relationships between their compositions. find that; (1) modules are comprised similar list gene products, (2) often...
Relationships between the genome, transcriptome, and metabolome underlie all evolved phenotypes. However, it has proved difficult to elucidate these relationships because of high number variables measured. A recently developed data analytic method for characterizing transcriptome can simplify interpretation by grouping genes into independently modulated sets (iModulons). Here, we demonstrate how iModulons reveal deep understanding effects causal mutations metabolic rewiring. We use adaptive...
ABSTRACT Fast growth phenotypes are achieved through optimal transcriptomic allocation, in which cells must balance tradeoffs resource allocation between diverse functions. One such stress readiness and unbridled E. coli has been termed the fear versus greed (f/g) tradeoff. Two specific RNA polymerase (RNAP) mutations observed adaptation to fast have previously shown affect f/g tradeoff, suggesting that genetic adaptations may be primed control allocation. Here, we conduct a greatly expanded...
Loss of epithelial polarity impacts organ development and function; it is also oncogenic. AMPK, a key sensor metabolic stress stabilizes cell-cell junctions maintains polarity; its activation by Metformin protects the barrier against suppresses tumorigenesis. How AMPK epithelium remains unknown. Here, we identify GIV/Girdin as novel effector whose phosphorylation at single site both necessary sufficient for strengthening mammalian tight preserving cell function in face energetic stress....
Abstract The bacterial respiratory electron transport system (ETS) is branched to allow condition-specific modulation of energy metabolism. There a detailed understanding the structural and biochemical features enzymes; however, holistic examination its plasticity lacking. Here we generate four strains Escherichia coli harboring unbranched ETS that pump 1, 2, 3, or 4 proton(s) per characterized them using combination synergistic methods (adaptive laboratory evolution, multi-omic analyses,...
Fit phenotypes are achieved through optimal transcriptomic allocation. Here, we performed a high-resolution, multi-scale study of the tradeoff between two key fitness phenotypes, stress response (fear) and growth (greed), in
iModulons-sets of co-expressed genes identified through independent component analysis (ICA) high-quality transcriptomic datasets-provide an unbiased, modular view organism's transcriptional regulatory network. Established in 2020, iModulonDB (iModulonDB.org) serves as a centralized repository curated iModulon sets, enabling users to explore iModulons and download the associated data. This update reflects significant expansion database-19 new ICA decompositions (+633%) spanning 8 925...
Abstract Energy homeostasis facilitated by the interplay of substrate-level and oxidative phosphorylation is crucial for bacterial adaptation to diverse substrates environments. To investigate how bioenergetic systems optimize under restrictive conditions, we evolved ETS variants with distinct proton-pumping efficiencies (1, 2, 3, or 4 proton(s) per electron) on succinate glycerol. These impose unique metabolic constraints: requires complete gluconeogenesis, while glycerol supports mixed...
After a cardiac event, proper treatment and care of the damaged tissue is crucial in restoring optimal function preventing future events. Recently, thymosin β4 has been found to play vital role cell health development by regulating angiogenesis, inflammatory responses, wound healing. We proposed that defined poly(ϵ-caprolactone) (PCL) nanoscaffolds coated with could efficiently differentiate murine-derived cardiomyocytes into functioning tissue. PCL were developed through electrospinning...
Pyruvate dehydrogenase complex (PDC) functions as the main determinant of respiro-fermentative balance because it converts pyruvate to acetyl-coenzyme A (CoA), which then enters TCA (tricarboxylic acid cycle). PDC is repressed by regulator (PdhR) in Escherichia coli. The deletion pdhR gene compromises fitness aerobic environments. We evolve E. coli strain examine its achievable growth rate and underlying adaptive strategies. find that (1) optimal proteome allocation critical achieving rate;...
Abstract Background Increased inflammation is a hallmark of COVID-19, with pulmonary and systemic identified in multiple cohorts patients. Definitive cellular molecular pathways driving severe forms this disease remain uncertain. Neutrophils, the most numerous leukocytes blood circulation, can contribute to immunopathology infections, inflammatory diseases acute respiratory distress syndrome (ARDS), primary cause morbidity mortality COVID-19. Changes neutrophil functions circulating cytokine...
It has proved challenging to quantitatively relate the proteome transcriptome on a per-gene basis. Recent advances in data analytics have enabled biologically meaningful modularization of bacterial transcriptome. We thus investigated whether matched datasets transcriptomes and proteomes from bacteria under diverse conditions could be modularized same way reveal novel relationships between their compositions. found that; 1) modules are comprised similar list gene products, 2) often represent...
Abstract Adaptive laboratory evolution (ALE) is able to generate microbial strains which exhibit extreme phenotypes, revealing fundamental biological adaptation mechanisms. Here, we use ALE evolve Escherichia coli that grow at temperatures as high 45.3°C, a temperature lethal wild type cells. The adopted hypermutator phenotype and employed multiple systems-level adaptations made global analysis of the DNA mutations difficult. Given challenge genomic level, were motivated uncover tolerance...
Summary Relationships between the genome, transcriptome, and metabolome underlie all evolved phenotypes. However, it has proved difficult to elucidate these relationships because of high number variables measured. A recently developed data analytic method for characterizing transcriptome can simplify interpretation by grouping genes into independently modulated sets (iModulons). Here, we demonstrate how iModulons reveal deep understanding effects causal mutations metabolic rewiring. We use...
ABSTRACT The bacterial lifestyle is plastic, requiring transcriptional, translational, and metabolic tailoring for survival. These dynamic cellular processes are energy intensive; therefore, flexible energetics requisite adaptive plasticity. An intricate network of complementary supplementary pathways exists in metabolism. There two main entry points electrons the aerobic electron transport system, NADH dehydrogenase (NDH) succinate (SDH), receiving from succinate, respectively. Aerobic...
ABSTRACT Diverse microbial species utilize redox shuttles to exchange electrons with their environment through mediated extracellular electron transfer (EET). This process maintains homeostasis and supports anaerobic survival across diverse communities. Although EET has been extensively leveraged for bioelectrocatalysis bioelectronics decades, fundamental questions remain about how these are reduced within cells bioenergetic implications. knowledge gap limits our understanding of the...
Background: Increased inflammation is a hallmark of COVID-19, with pulmonary and systemic identified in multiple cohorts patients. Definitive cellular molecular pathways driving severe forms this disease remain uncertain. Neutrophils, the most numerous leukocytes blood circulation, can contribute to immunopathology infections, inflammatory diseases acute respiratory distress syndrome (ARDS), primary cause morbidity mortality COVID-19. Neutrophilia, elevated neutrophil:lymphocyte ratios,...
Relationships between the genome, transcriptome, and metabolome underlie all evolved phenotypes. However, it has proved difficult to elucidate these relationships because of high number variables measured. A recently developed data analytic method for characterizing transcriptome can simplify interpretation by grouping genes into independently modulated sets (iModulons). Here, we demonstrate how iModulons reveal deep understanding effects causal mutations metabolic rewiring. We use adaptive...
Respiration requires organisms to have an electron transport system (ETS) for the generation of proton motive force across membrane that drives ATP synthase. Although molecular details ETS are well studied and constitute textbook material, few studies appeared elucidate its systems biology. The most thermodynamically efficient consists two enzymes, NADH: quinone oxidoreductase (NqRED) a dioxygen reductase (O 2 RED), which facilitate shuttling electrons from NADH oxygen. However, evolution...