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6 results on '"Tsimring, Lev S."'

1. Statistical Theory of Asymmetric Damage Segregation in Clonal Cell Populations

Author

Pikovsky, Arkady and Tsimring, Lev S.

Subjects
Quantitative Biology - Populations and Evolution, Nonlinear Sciences - Adaptation and Self-Organizing Systems, Physics - Biological Physics
Abstract

Asymmetric damage segregation (ADS) is ubiquitous among unicellular organisms: After a mother cell divides, its two daughter cells receive sometimes slightly, sometimes strongly different fractions of damaged proteins accumulated in the mother cell. Previous studies demonstrated that ADS provides a selective advantage over symmetrically dividing cells by rejuvenating and perpetuating the population as a whole. In this work we focus on the statistical properties of damage in individual lineages and the overall damage distributions in growing populations for a variety of ADS models with different rules governing damage accumulation, segregation, and the lifetime dependence on damage. We show that for a large class of deterministic ADS rules the trajectories of damage along the lineages are chaotic, and the distributions of damage in cells born at a given time asymptotically becomes fractal. By exploiting the analogy of linear ADS models with the Iterated Function Systems known in chaos theory, we derive the Frobenius-Perron equation for the stationary damage density distribution and analytically compute the damage distribution moments and fractal dimensions. We also investigate nonlinear and stochastic variants of ADS models and show the robustness of the salient features of the damage distributions., Comment: Mathematical Biosciences, 2023 (in press)

Published
2023

2. Age-dependent aggregation of ribosomal RNA-binding proteins links deterioration in chromatin stability with challenges to proteostasis

Author

Paxman, Julie, Zhou, Zhen, O'Laughlin, Richard, Liu, Yuting, Li, Yang, Tian, Wanying, Su, Hetian, Jiang, Yanfei, Holness, Shayna E, Stasiowski, Elizabeth, Tsimring, Lev S, Pillus, Lorraine, Hasty, Jeff, and Hao, Nan

Subjects
Genetics, Aging, 1.1 Normal biological development and functioning, Underpinning research, Generic health relevance, Silent Information Regulator Proteins, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Proteostasis, Chromatin, Sirtuin 2, Lysine, Saccharomyces cerevisiae, DNA, Ribosomal, RNA, Ribosomal, RNA-Binding Proteins, single-cell aging, proteostasis, time-lapse imaging, chromatin stability, microfluidics, S, cerevisiae, S. cerevisiae, cell biology, computational biology, systems biology, Biochemistry and Cell Biology
Abstract

Chromatin instability and protein homeostasis (proteostasis) stress are two well-established hallmarks of aging, which have been considered largely independent of each other. Using microfluidics and single-cell imaging approaches, we observed that, during the replicative aging of Saccharomyces cerevisiae, a challenge to proteostasis occurs specifically in the fraction of cells with decreased stability within the ribosomal DNA (rDNA). A screen of 170 yeast RNA-binding proteins identified ribosomal RNA (rRNA)-binding proteins as the most enriched group that aggregate upon a decrease in rDNA stability induced by inhibition of a conserved lysine deacetylase Sir2. Further, loss of rDNA stability induces age-dependent aggregation of rRNA-binding proteins through aberrant overproduction of rRNAs. These aggregates contribute to age-induced proteostasis decline and limit cellular lifespan. Our findings reveal a mechanism underlying the interconnection between chromatin instability and proteostasis stress and highlight the importance of cell-to-cell variability in aging processes.

Published
2022

5. Age-dependent aggregation of ribosomal RNA-binding proteins links deterioration in chromatin stability with challenges to proteostasis

Author

Paxman, Julie, primary, Zhou, Zhen, primary, O'Laughlin, Richard, additional, Liu, Yuting, additional, Li, Yang, additional, Tian, Wanying, additional, Su, Hetian, additional, Jiang, Yanfei, additional, Holness, Shayna E, additional, Stasiowski, Elizabeth, additional, Tsimring, Lev S, additional, Pillus, Lorraine, additional, Hasty, Jeff, additional, and Hao, Nan, additional

Published
2022
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6. Statistical Theory of Asymmetric Damage Segregation in Clonal Cell Populations.

Author

Pikovsky A and Tsimring LS

Abstract

Asymmetric damage segregation (ADS) is ubiquitous among unicellular organisms: After a mother cell divides, its two daughter cells receive sometimes slightly, sometimes strongly different fractions of damaged proteins accumulated in the mother cell. Previous studies demonstrated that ADS provides a selective advantage over symmetrically dividing cells by rejuvenating and perpetuating the population as a whole. In this work we focus on the statistical properties of damage in individual lineages and the overall damage distributions in growing populations for a variety of ADS models with different rules governing damage accumulation, segregation, and the lifetime dependence on damage. We show that for a large class of deterministic ADS rules the trajectories of damage along the lineages are chaotic, and the distributions of damage in cells born at a given time asymptotically becomes fractal. By exploiting the analogy of linear ADS models with the Iterated Function Systems known in chaos theory, we derive the Frobenius-Perron equation for the stationary damage density distribution and analytically compute the damage distribution moments and fractal dimensions. We also investigate nonlinear and stochastic variants of ADS models and show the robustness of the salient features of the damage distributions.

Published
2023

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