A5065881412- Cancer-related Molecular Pathways
- Cell Image Analysis Techniques
- Origins and Evolution of Life
- Genetics, Aging, and Longevity in Model Organisms
- Protein Structure and Dynamics
- Cellular Mechanics and Interactions
- Gene Regulatory Network Analysis
- Advanced Fluorescence Microscopy Techniques
- Cancer, Hypoxia, and Metabolism
- CRISPR and Genetic Engineering
- Microbial Metabolic Engineering and Bioproduction
- Amino Acid Enzymes and Metabolism
- Adipose Tissue and Metabolism
- Viral Infectious Diseases and Gene Expression in Insects
- RNA and protein synthesis mechanisms
- Pancreatic function and diabetes
- Microtubule and mitosis dynamics
- Fungal and yeast genetics research
- Mitochondrial Function and Pathology
- Hedgehog Signaling Pathway Studies
- Genetics, Bioinformatics, and Biomedical Research
- Cancer Research and Treatments
- Single-cell and spatial transcriptomics
- Epigenetics and DNA Methylation
- Bioinformatics and Genomic Networks
Hospital for Sick Children
2015-2025
University of Toronto
2017-2024
Great Ormond Street Hospital
2024
SickKids Foundation
2021-2024
University College London
2024
Center for Systems Biology
2009-2013
Harvard University
2009-2013
Weizmann Institute of Science
2002-2010
More Glycine, Please To better characterize metabolic properties of cancer cells, Jain et al. (p. 1040 ; see the Perspective by Tomita and Kami ) measured systematically concentrations hundreds metabolites in cell culture medium which 60 different lines were growing. The fastest growing cells tended to consume glycine, whereas more slowly excreted some glycine. rapidly appeared need glycine for synthesis purine nucleotides required continued DNA. Interfering with metabolism slowed growth...
A long-standing question in biology is whether there an intrinsic mechanism for coordinating growth and the cell cycle metazoan cells. We examined size distributions populations of lymphoblasts applied a mathematical analysis to calculate how rates vary with both cycle. Our results show that rate size-dependent throughout After initial suppression, rapid increase during G1 phase, followed by period constant exponential growth. The probability division varies independently age. conclude...
Functional redundancies, generated by gene duplications, are highly widespread throughout all known genomes. One consequence of these redundancies is a tremendous increase to the robustness organisms mutations and other stresses. Yet, this very also renders redundancy evolutionarily unstable, it is, thus, predicted have only transient lifetime. In contrast, numerous reports describe instances functional overlaps that been conserved extended evolutionary periods. More interestingly, many such...
Cell size uniformity in healthy tissues suggests that control mechanisms might coordinate cell growth and division. We derived a method to assay whether cellular rates depend on size, by monitoring how variance changes as cells grow. Our data revealed that, twice during the cycle, are selectively increased small reduced large cells, ensuring uniformity. This regulation was also observed directly nuclear live cells. detected cell-size-dependent adjustments of G1 length, which further reduce...
Animal cells within a tissue typically display striking regularity in their size. To date, the molecular mechanisms that control this uniformity are still unknown. We have previously shown size animal is promoted, part, by size-dependent regulation of G1 length. identify underlying process, we performed large-scale small molecule screen and found p38 MAPK pathway involved coordinating cell cycle progression. Small higher activity spend more time than larger cells. Inhibition leads to loss...
Identifying the chemical regulators of biological pathways is a time-consuming bottleneck in developing therapeutics and research compounds. Typically, thousands to millions candidate small molecules are tested target-based biochemical screens or phenotypic cell-based screens, both expensive experiments customized each disease. Here, our uncustomized, virtual, profile-based screening approach instead identifies compounds that match based on information public cell image data, created using...
The widely observed dispensability of duplicate genes is typically interpreted to suggest that a proportion the pairs are at least partially redundant in their functions, thus allowing for compensatory affects. However, because redundancy expected be evolutionarily short lived, there currently debate on both duplicates and functional importance. Here, we examined these interactions by relying genome wide data analysis, followed experiments literature mining yeast. Our data, thus, strongly...
Highlights•Mouse pancreatic acinar and beta cells grow dramatically during postnatal life•Acinar cell growth is a major contributor to pancreas in mice•Postnatal of the human relies entirely on increased number•Acinar size inversely correlates with lifespan among 24 mammalian speciesSummaryDevelopmental processes different mammals are thought share fundamental cellular mechanisms. We report dramatic increase development rodents, accounting for much organ after birth. Hypertrophy involves...
mTORC1 regulates cellular growth and is activated by factors essential amino acids such as Leu. Leu enters cells via the transporter LAT1-4F2hc (LAT1). Here we show that Na+/K+/2Cl- cotransporter NKCC1 (SLC12A2), a known regulator of cell volume, present in complex with LAT1. We further depletion or deletion enhances LAT1 activity, well activation Akt Erk, leading to cells, colonic organoids, mouse colon. Moreover, reduces intracellular Na+ concentration volume (size) mass stimulates...
Abstract Senescent cells typically have an enlarged cell size but the reason for this has not been fully elucidated. As abnormal may alter protein concentrations and cellular functionality, we used proteomic data from 59 unperturbed human lines to systematically characterize cell-size dependent changes in intracellular organelle content. Increase leads ubiquitous transcriptionally post-transcriptionally regulated reorganization dilution of proteome. Many known senescence proteins display...
Ion channels represent a large class of drug targets, but their role in brain cancer is underexplored. Here, we identify that chloride intracellular channel 1 (CLIC1) overexpressed human central nervous system malignancies, including medulloblastoma, common pediatric cancer. While global knockout does not overtly affect mouse development, genetic deletion CLIC1 suppresses medulloblastoma growth xenograft and genetically engineered models. Mechanistically, enriches to the plasma membrane...
Proliferating animal cells maintain a stable size distribution over generations despite fluctuations in cell growth and division size. Previously, we showed that control involves both checkpoints, which delay cycle progression small cells, size-dependent regulation of mass accumulation rates (Ginzberg et al., 2018). While previously identified the p38 MAPK pathway as key regulator mammalian checkpoint (S. Liu 2018), mechanism rate has remained elusive. Here, quantified global protein...
Abstract While multiplexing samples using DNA barcoding revolutionized the pace of biomedical discovery, live imaging-based applications has been limited by number fluorescent proteins that can be deconvoluted common microscopy equipment. To address this limitation, we develop visual barcodes discriminate clonal identity single cells different are targeted to specific subcellular locations. We demonstrate deconvolution these is highly accurate and robust many cellular perturbations. then use...
Embryos repair wounds rapidly, with no inflammation or scarring, in a process that involves polarization of the actomyosin cytoskeleton. Actomyosin results assembly contractile cable around wound drives closure. Here, we demonstrate is not sufficient for rapid Drosophila embryos. We show wounding causes activation serine/threonine kinase p38 mitogen-activated protein (MAPK) cells adjacent to wound. reduces levels wound-induced reactive oxygen species wound, limiting size. In addition,...
Abstract Background An important facet of early biological evolution is the selection chiral enantiomers for molecules such as amino acids and sugars. The origin this symmetry breaking a long-standing question in molecular evolution. Previous models addressing include particular kinetic properties autocatalysis or negative cross catalysis. Results We propose here more general formalism enantioselection, based on our previously described Graded Autocatalysis Replication Domain (GARD) model...
Molecular Chirality is of central interest in biological studies because enantiomeric compounds, while indistinguishable by most inanimate systems, show profoundly different properties biochemical environments. Enantioselective separation methods, based on the differential recognition two optical isomers a chiral selector, have been amply documented. Also, great effort has directed towards theoretical understanding fundamental mechanisms underlying process. Here we report comprehensive data...