A5006245669- Evolution and Genetic Dynamics
- RNA and protein synthesis mechanisms
- Bacterial Genetics and Biotechnology
- RNA Research and Splicing
- Genomics and Chromatin Dynamics
- Gene Regulatory Network Analysis
- Genomics and Phylogenetic Studies
- CRISPR and Genetic Engineering
- RNA modifications and cancer
- Fungal and yeast genetics research
- Bioinformatics and Genomic Networks
- Microbial Metabolic Engineering and Bioproduction
- Antibiotic Resistance in Bacteria
- Bacteriophages and microbial interactions
- Neural dynamics and brain function
- Neural Networks and Applications
- Single-cell and spatial transcriptomics
- Advanced Memory and Neural Computing
- Molecular Biology Techniques and Applications
- Chromosomal and Genetic Variations
- ATP Synthase and ATPases Research
- Adipose Tissue and Metabolism
- Evolutionary Game Theory and Cooperation
- Animal Genetics and Reproduction
- Advanced Proteomics Techniques and Applications
Columbia University
2015-2025
Columbia University Irving Medical Center
2013-2023
Center for Systems Biology
2012-2014
New York Proton Center
2014
Princeton University
2003-2012
Harvard University
1998-2000
Microglia are resident immune cells of the CNS that activated by infection, neuronal injury, and inflammation. Here, we utilize flow cytometry deep RNA sequencing acutely isolated spinal cord microglia to define their activation in vivo. Analysis resting identified 29 genes distinguish from other peripheral macrophages/monocytes. We then analyzed molecular changes during neurodegenerative disease using SOD1G93A mouse model amyotrophic lateral sclerosis (ALS). found not derived infiltrating...
The homeostatic framework has dominated our understanding of cellular physiology. We question whether homeostasis alone adequately explains microbial responses to environmental stimuli, and explore the capacity intracellular networks for predictive behavior in a fashion similar metazoan nervous systems. show that silico biochemical networks, evolving randomly under precisely defined complex habitats, capture dynamical, multidimensional structure diverse environments by forming internal...
The metabolic capabilities and regulatory networks of bacteria have been optimized by evolution in response to selective pressures present each species' native ecological niche. In a new environment, however, the same may grow poorly due constraints or biochemical deficiencies. Adaptation such conditions can proceed through acquisition cellular functionality gain function mutations via modulation networks. Using selection experiments on transposon-mutagenized libraries bacteria, we...
Abstract Patients with primary mitochondrial oxidative phosphorylation (OxPhos) defects present fatigue and multi-system disorders, are often lean, die prematurely, but the mechanistic basis for this clinical picture remains unclear. By integrating data from 17 cohorts of patients diseases ( n = 690) we find evidence that these disorders increase resting energy expenditure, a state termed hypermetabolism . We examine phenomenon longitudinally in patient-derived fibroblasts multiple donors....
During the maternal-to-zygotic transition, a developing embryo integrates post-transcriptional regulation of maternal mRNAs with transcriptional activation its own genome. By combining chromosomal ablation in Drosophila microarray analysis, we characterized basis this integration. We show that expression profile for at least one third zygotically active genes is coupled to concomitant degradation corresponding mRNAs. The uses transcription and generate localized patterns expression, zygotic...
We have developed a powerful experimental framework that combines competitive selection and microarray-based genetic footprinting to comprehensively reveal the basis of bacterial behaviors. Application this method Escherichia coli motility identifies 95% known flagellar chemotaxis genes, reveals three dozen novel loci that, varying degrees through diverse mechanisms, affect motility. To probe network context in which these genes function, we uncovers genome-wide epistatic interactions...
Antibiotic exposure rapidly selects for more resistant bacterial strains, and both a drug's chemical structure bacterium's cellular network affect the types of mutations acquired.To better characterize genetic determinants antibiotic susceptibility, we exposed transposon-mutagenized library Escherichia coli to each 17 antibiotics that encompass wide range drug classes mechanisms action. Propagating multiple generations with concentrations moderately inhibited growth isogenic parental strain...
Phenotypic heterogeneity displayed by a clonal bacterial population permits small fraction of cells to survive prolonged exposure antibiotics. Although first described over 60 y ago, the molecular mechanisms underlying this behavior, termed persistence, remain largely unknown. To systematically explore genetic basis we selected library transposon-mutagenized Escherichia coli for survival multiple rounds lethal ampicillin exposure. Application microarray-based footprinting revealed large...
Addition of glucose to starved yeast cells elicits a dramatic restructuring the transcriptional and metabolic state cell. While many components signaling network responsible for this response have been identified, comprehensive view is lacking. We used global analysis gene expression assess roles small GTP-binding proteins, Ras2 Gpa2, in mediating glucose. find that 90% changes cell attendant on addition are recapitulated by activation or Gpa2. In addition, we protein kinase A (PKA) mediates...
Abstract We describe a powerful new approach for discovering globally conserved regulatory elements between two genomes. The method is fast, simple and comprehensive, without requiring alignments. Its application to pairs of yeasts, worms, flies mammals yields large number known novel putative elements. Many these are validated by independent biological observations, have spatial and/or orientation biases, co-conserved with other show surprising conservation across phylogenetic distances.
One of the most prominent features at mid-blastula transition (MBT)observed in embryos is a pause cell cycle regulated by nucleocytoplasmic (N/C) ratio. By using chromosome rearrangements to manipulate DNA content embryos, we determined that threshold for this Drosophila about 70% normally present 14. Embryos with contents around value show intermediate behaviors. Some 14, some 15,and form patches arrested different mitotic cycles. A second feature MBT massive increase zygotic transcription...