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Quantitative Modeling and Analysis o...

Ba, Qinle.

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Quantitative Modeling and Analysis of the Whole-Cell Scale Dynamic Organization of Lysosomes.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Quantitative Modeling and Analysis of the Whole-Cell Scale Dynamic Organization of Lysosomes./
Author:	Ba, Qinle.
Published:	Ann Arbor : ProQuest Dissertations & Theses, : 2018,
Description:	134 p.
Notes:	Source: Dissertation Abstracts International, Volume: 80-03(E), Section: B.
Contained By:	Dissertation Abstracts International80-03B(E).
Subject:	Cellular biology. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=10976188
ISBN:	9780438631052

Quantitative Modeling and Analysis of the Whole-Cell Scale Dynamic Organization of Lysosomes.
Ba, Qinle.

Quantitative Modeling and Analysis of the Whole-Cell Scale Dynamic Organization of Lysosomes. - Ann Arbor : ProQuest Dissertations & Theses, 2018 - 134 p.

Source: Dissertation Abstracts International, Volume: 80-03(E), Section: B.

Thesis (Ph.D.)--Carnegie Mellon University, 2018.

In eukaryotic cells, lysosomes are dynamic organelles spatially positioned in the cytoplasm for degrading macromolecules and serving as metabolic signaling centers. A fundamental yet unanswered question is whether and, if so, how individual lysosomes are organized spatially to coordinate and integrate their functions. To address this question, we developed image-based computational methods to systematically investigate the dynamic spatial organization of lysosomes and lysosomal interactions with partner organelles, especially the endoplasmic reticulum (ER) and endosomes. We found that lysosomes are spatially organized rather than randomly distributed. In individual cells, lysosomal distributions are stable over time, while among different cells lysosomal distributions are distinct. The cytoskeleton, ER and lysosomal biogenesis/autophagy are required for maintaining these distributions. Throughout the intracellular space, lysosomes form dynamic clusters of various sizes that can split and merge over time. The formation and dynamics of clusters are associated with microtubule-mediated active transport and local ER structural properties, but do not depend on lysosomal interaction with endosomes or spatial exclusion by mitochondria. The increased lysosomal density in clusters promotes lysosomal interactions with late endosomes. Due to the importance of ER in spatially positioning lysosomes, we analyzed the network properties of ER, and found that the ER network may to be efficient only for local functional signal spreading, suggesting that the interaction between ER and lysosomal clusters can be locally and spatially heterogeneous regulated. Together, this research reveals whole-cell scale dynamic organization of lysosomes and how their interactions with ER and endosomes are mediated at the systems level in the entire intracellular space.

ISBN: 9780438631052Subjects--Topical Terms:

3172791
Cellular biology.

Quantitative Modeling and Analysis of the Whole-Cell Scale Dynamic Organization of Lysosomes.
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245 1 0 $a Quantitative Modeling and Analysis of the Whole-Cell Scale Dynamic Organization of Lysosomes.
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300 $a 134 p.
500 $a Source: Dissertation Abstracts International, Volume: 80-03(E), Section: B.
500 $a Adviser: Ge Yang.
502 $a Thesis (Ph.D.)--Carnegie Mellon University, 2018.
520 $a In eukaryotic cells, lysosomes are dynamic organelles spatially positioned in the cytoplasm for degrading macromolecules and serving as metabolic signaling centers. A fundamental yet unanswered question is whether and, if so, how individual lysosomes are organized spatially to coordinate and integrate their functions. To address this question, we developed image-based computational methods to systematically investigate the dynamic spatial organization of lysosomes and lysosomal interactions with partner organelles, especially the endoplasmic reticulum (ER) and endosomes. We found that lysosomes are spatially organized rather than randomly distributed. In individual cells, lysosomal distributions are stable over time, while among different cells lysosomal distributions are distinct. The cytoskeleton, ER and lysosomal biogenesis/autophagy are required for maintaining these distributions. Throughout the intracellular space, lysosomes form dynamic clusters of various sizes that can split and merge over time. The formation and dynamics of clusters are associated with microtubule-mediated active transport and local ER structural properties, but do not depend on lysosomal interaction with endosomes or spatial exclusion by mitochondria. The increased lysosomal density in clusters promotes lysosomal interactions with late endosomes. Due to the importance of ER in spatially positioning lysosomes, we analyzed the network properties of ER, and found that the ER network may to be efficient only for local functional signal spreading, suggesting that the interaction between ER and lysosomal clusters can be locally and spatially heterogeneous regulated. Together, this research reveals whole-cell scale dynamic organization of lysosomes and how their interactions with ER and endosomes are mediated at the systems level in the entire intracellular space.
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