A5034248406- Genetics, Aging, and Longevity in Model Organisms
- Circadian rhythm and melatonin
- Spaceflight effects on biology
- Plant Molecular Biology Research
- RNA modifications and cancer
- Genomics and Chromatin Dynamics
- Heat shock proteins research
- FOXO transcription factor regulation
- Ubiquitin and proteasome pathways
- Image Processing Techniques and Applications
- RNA and protein synthesis mechanisms
- Diabetes and associated disorders
- Chromosomal and Genetic Variations
- Autophagy in Disease and Therapy
- Nanoparticles: synthesis and applications
- Pancreatic function and diabetes
- Bacterial Identification and Susceptibility Testing
- Aging and Gerontology Research
- Analytical Chemistry and Sensors
- Bioinformatics and Genomic Networks
- Electrostatics and Colloid Interactions
- Dietary Effects on Health
- Polymer Surface Interaction Studies
- Cell Image Analysis Techniques
- Neurobiology and Insect Physiology Research
Universitat Pompeu Fabra
2018-2024
Centre for Genomic Regulation
2018-2024
Institute of Science and Technology
2024
Center for Systems Biology
2013-2018
Harvard University
2013-2018
Princeton University
2002
Institute of Theoretical and Experimental Biophysics
2002
Abstract Advances in microscopy hold great promise for allowing quantitative and precise measurement of morphological molecular phenomena at the single-cell level bacteria; however, potential this approach is ultimately limited by availability methods to faithfully segment cells independent their or optical characteristics. Here, we present Omnipose, a deep neural network image-segmentation algorithm. Unique outputs such as gradient distance field allow Omnipose accurately on which current...
The ability to perceive and respond harmful conditions is crucial for the survival of any organism. transcription factor DAF-16/FOXO central these responses, relaying distress signals into expression stress resistance longevity promoting genes. However, its sufficiency in fulfilling this complex task has remained unclear. Using C. elegans, we show that DAF-16 does not function alone but as part a transcriptional regulatory module, together with HLH-30/TFEB. Under conditions, both factors...
Insulin-like peptides (ILPs) play highly conserved roles in development and physiology. Most animal genomes encode multiple ILPs. Here we identify mechanisms for how the forty Caenorhabditis elegans ILPs coordinate diverse processes, including development, reproduction, longevity several specific stress responses. Our systematic studies an ILP-based combinatorial code these phenotypes characterized by substantial functional specificity diversity rather than global redundancy. Notably, show...
Aging strongly influences human morbidity and mortality. Thus, aging-preventive compounds could greatly improve our health lifespan. Here we screened for such compounds, known as geroprotectors, employing the power of transcriptomics to predict biological age. Using age-stratified tissue transcriptomes machine learning, generated age classifiers applied these transcriptomic changes induced by 1,309 different in cells, ranking their ability induce a "youthful" transcriptional state. Testing...
Cells adjust their proteome to environment. Most prominently, ribosome expression scales near linearly with the cellular growth rate provide sufficient translational capacity while preventing metabolically wasteful ribosomal excess. In microbes, such adjustments can passively perpetuate through symmetric cell division. However, in animals, a passive propagation is hindered by separation between soma and germline. This raises crucial question whether of animals reset at every generation or be...
RNA-sequencing provides high-dimensional, quantitative descriptions of the physiologic state cells, tissues, organs, and whole organisms. RNA-Seq protocols based on 96 364-well plates allow for a wider range experimental designs compared to droplet sequencing methods, but are less scalable due practical challenges plate-based liquid handling. Here, we present STOMP-seq, an method that extends Smart-seq2 include sample barcodes 5' end amplified transcript. The additional samples be pooled...
Many pathogens secrete toxins that target key host processes resulting in the activation of immune pathways. The secreted Pseudomonas aeruginosa toxin Exotoxin A (ToxA) disrupts intestinal protein synthesis, which triggers induction a subset P. aeruginosa-response genes nematode Caenorhabditis elegans.We show here one ToxA-induced C. elegans gene, Tribbles pseudokinase ortholog nipi-3, is essential for survival following exposure to or ToxA. We find NIPI-3 mediates post-developmental...
Hydrogen peroxide is the preeminent chemical weapon that organisms use for combat. Individual cells rely on conserved defenses to prevent and repair peroxide-induced damage, but whether similar might be coordinated across in animals remains poorly understood. Here, we identify a neuronal circuit nematode Caenorhabditis elegans processes information perceived by two sensory neurons control induction of hydrogen organism. We found catalases produced Escherichia coli, nematode’s food source,...
Aging involves a transition from youthful vigor to geriatric infirmity and death. Individuals who remain vigorous longer tend live longer, within isogenic populations of C . elegan s the timing age-associated movement cessation (VMC) is highly correlated with lifespan. Yet, many mutations interventions in aging alter proportion lifespan spent moving vigorously, appearing “uncouple” To clarify relationship between cessation, death, physical declines that determine their timing, we developed...
Hydrogen peroxide is the most common reactive chemical that organisms face on microbial battlefield. The rate with which hydrogen damages biomolecules required for life increases temperature, yet little known about how cope this temperature-dependent threat. Here, we show
Chromatin architecture is a fundamental mediator of genome function. Fasting major environmental cue across the animal kingdom. Yet, how it impacts on 3D organization unknown. Here, we show that fasting induces reversible and large-scale spatial reorganization chromatin in
Genetically identical animals kept in a constant environment display wide distribution of lifespans, reflecting large non-genetic, stochastic aspect to aging conserved across all organisms studied. This component means that order understand and identify successful interventions extend the lifespan or improve health, researchers must monitor populations experimental simultaneously. Traditional manual death scoring limits throughput scale required for large-scale hypothesis testing, leading...
Abstract In environments with fluctuating nutrient abundance, organisms must survive periods of starvation, yet quickly resume growth upon food encounter. A tradeoff between these objectives is well-documented in microbes, where it caused by the need to partition total cellular protein content growth- and survival-enhancing proteins. However, molecular mechanisms growth-survival tradeoffs multicellular animals remain largely unknown. Here, we addressed this mechanism for C. elegans measuring...
ABSTRACT The physiological mechanisms governing health and disease exhibit complex interactions between multiple genes gene products. To study the dynamics of living systems, researchers need experimental methods capable producing calibrated, quantitative perturbations in vivo — that cannot be obtained using classical genetics, RNAi interference, or small molecule drugs. Recently, an auxin-inducible degron (AID) system has been developed to allow targeted degradation proteins small-molecule...
Abstract Across all taxa of life, individuals within a species exhibit variable lifespans. Differences in genotype or environment are not sufficient to explain this variance, as even isogenic Caenorhabditis elegans nematodes reared under uniform conditions show significant variability lifespan. To investigate phenomenon, we used lifespan‐predictive biomarkers isolate, at mid‐adulthood, prospectively long‐ and short‐lived from an otherwise identical population. We selected two which...
Abstract Individuals who remain vigorous longer tend to live longer, supporting the design of predictive behavioral biomarkers aging. In C. elegans , timing age-associated movement cessation (VMC) and lifespan correlate strongly between individuals. However, many genetic pharmaceutical interventions that alter aging produce disproportional effects on VMC lifespan, appearing “uncouple” rate lifespan. To study causal structure underlying such uncoupling, we developed a high-throughput,...
Summary Aging is a major risk factor for human morbidity and mortality. Thus, the identification of compounds that defer aging, also known as ‘geroprotectors’, could greatly improve our health promote longer life. Here we screened geroprotectors, employing power transcriptomics to predict biological age. We used age-stratified tissue transcriptomes generate machine-learning-based classifiers capable distinguishing from young versus old individuals. Then applied these induced by 1300...