東華大學圖書館 |

Language: English

Help

回圖書館首頁

手機版館藏查詢

Back

Switch To: Labeled | MARC Mode | ISBD

Characterization of Nuclear Degradat...

Yalonetskaya, Alla.

Linked to FindBook

Google Book

Amazon

博客來

Characterization of Nuclear Degradation Dynamics During Cell Death and Modeling Laminopathies using CRISPR/Cas9 in Drosophila melanogaster.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Characterization of Nuclear Degradation Dynamics During Cell Death and Modeling Laminopathies using CRISPR/Cas9 in Drosophila melanogaster./
Author:	Yalonetskaya, Alla.
Published:	Ann Arbor : ProQuest Dissertations & Theses, : 2019,
Description:	233 p.
Notes:	Source: Dissertations Abstracts International, Volume: 81-10, Section: B.
Contained By:	Dissertations Abstracts International81-10B.
Subject:	Cellular biology. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=22619925
ISBN:	9781658425230

Characterization of Nuclear Degradation Dynamics During Cell Death and Modeling Laminopathies using CRISPR/Cas9 in Drosophila melanogaster.
Yalonetskaya, Alla.

Characterization of Nuclear Degradation Dynamics During Cell Death and Modeling Laminopathies using CRISPR/Cas9 in Drosophila melanogaster. - Ann Arbor : ProQuest Dissertations & Theses, 2019 - 233 p.

Source: Dissertations Abstracts International, Volume: 81-10, Section: B.

Thesis (Ph.D.)--Boston University, 2019.

This item must not be sold to any third party vendors.

Characterization of apoptosis, a caspase-dependent cell death program, has led to diverse insights into development, tissue homeostasis, and numerous diseases. About a dozen other distinct modes of regulated cell death have been identified, but our understanding of them is incomplete. Of particular interest is elucidating the process of nuclear degradation in non-apoptotic cell death, as lingering nuclear debris can be toxic. During apoptosis, caspases cleave nuclear components, but caspase-independent mechanisms of nuclear breakdown are not fully understood. The Drosophila melanogaster ovary is an excellent model to address differences in nuclear breakdown, since both apoptotic and non-apoptotic cell death occur during oogenesis. In mid-stages of oogenesis, germline-derived NCs die by apoptosis, while in late stages, germline-derived NCs degenerate by non-apoptotic cell death.A comparative analysis was performed, focusing on the caspase substrate nuclear Lamin and distinct differences in nuclear degradation events were found. Our data revealed a series of nuclear architecture changes during non-apoptotic cell death. The engulfment receptor Draper and phagocytic machinery were non-autonomously required for Lamin degradation, and the lysosomal protease CP1 facilitated Lamin degradation in non-apoptotic nurse cell (NC) death. We next examined the effects of expressing caspase-resistant Lamin and found that it impaired nuclear degradation during apoptosis. In contrast, nuclear degradation in non-apoptotic cell death was impaired by the overexpression of wild-type Lamin, supporting that Lamin degradation mechanisms are distinct in these two modes of cell death.Nuclear lamins, specifically isoforms encoded by the LMNA gene, are associated with the greatest number of disease-causing mutations in humans. Interestingly, one of these mutations occurs in the caspase-cleavage site and is associated with familial partial lipodystrophy, type 2 (FPLD2). To develop a Drosophila model of this disease, CRISPR/Cas9 was used to introduce a point mutation in lamC, the Drosophila homolog of LMNA. The fat body cells of mutant larvae were found to have altered lamin organization.Altogether, the work in this dissertation identifies novel nuclear degradation dynamics in a non-apoptotic cell death. In addition, this work describes a fly model system for laminopathy mutations in humans.

ISBN: 9781658425230Subjects--Topical Terms:

3172791
Cellular biology.
Subjects--Index Terms:

Cell death

Characterization of Nuclear Degradation Dynamics During Cell Death and Modeling Laminopathies using CRISPR/Cas9 in Drosophila melanogaster.
LDR:03608nmm a2200373 4500 001 2272775
005 20201105110220.5
008 220629s2019 ||||||||||||||||| ||eng d
020 $a 9781658425230
035 $a (MiAaPQ)AAI22619925
035 $a AAI22619925
040 $a MiAaPQ $c MiAaPQ
100 1 $a Yalonetskaya, Alla. $3 3550202
245 1 0 $a Characterization of Nuclear Degradation Dynamics During Cell Death and Modeling Laminopathies using CRISPR/Cas9 in Drosophila melanogaster.
260 1 $a Ann Arbor : $b ProQuest Dissertations & Theses, $c 2019
300 $a 233 p.
500 $a Source: Dissertations Abstracts International, Volume: 81-10, Section: B.
500 $a Advisor: McCall, Kimberly.
502 $a Thesis (Ph.D.)--Boston University, 2019.
506 $a This item must not be sold to any third party vendors.
520 $a Characterization of apoptosis, a caspase-dependent cell death program, has led to diverse insights into development, tissue homeostasis, and numerous diseases. About a dozen other distinct modes of regulated cell death have been identified, but our understanding of them is incomplete. Of particular interest is elucidating the process of nuclear degradation in non-apoptotic cell death, as lingering nuclear debris can be toxic. During apoptosis, caspases cleave nuclear components, but caspase-independent mechanisms of nuclear breakdown are not fully understood. The Drosophila melanogaster ovary is an excellent model to address differences in nuclear breakdown, since both apoptotic and non-apoptotic cell death occur during oogenesis. In mid-stages of oogenesis, germline-derived NCs die by apoptosis, while in late stages, germline-derived NCs degenerate by non-apoptotic cell death.A comparative analysis was performed, focusing on the caspase substrate nuclear Lamin and distinct differences in nuclear degradation events were found. Our data revealed a series of nuclear architecture changes during non-apoptotic cell death. The engulfment receptor Draper and phagocytic machinery were non-autonomously required for Lamin degradation, and the lysosomal protease CP1 facilitated Lamin degradation in non-apoptotic nurse cell (NC) death. We next examined the effects of expressing caspase-resistant Lamin and found that it impaired nuclear degradation during apoptosis. In contrast, nuclear degradation in non-apoptotic cell death was impaired by the overexpression of wild-type Lamin, supporting that Lamin degradation mechanisms are distinct in these two modes of cell death.Nuclear lamins, specifically isoforms encoded by the LMNA gene, are associated with the greatest number of disease-causing mutations in humans. Interestingly, one of these mutations occurs in the caspase-cleavage site and is associated with familial partial lipodystrophy, type 2 (FPLD2). To develop a Drosophila model of this disease, CRISPR/Cas9 was used to introduce a point mutation in lamC, the Drosophila homolog of LMNA. The fat body cells of mutant larvae were found to have altered lamin organization.Altogether, the work in this dissertation identifies novel nuclear degradation dynamics in a non-apoptotic cell death. In addition, this work describes a fly model system for laminopathy mutations in humans.
590 $a School code: 0017.
650 4 $a Cellular biology. $3 3172791
650 4 $a Molecular biology. $3 517296
653 $a Cell death
653 $a Drosophila
653 $a Lamin
653 $a Non-apoptotic
653 $a Nucleus
653 $a Nurse cell
690 $a 0379
690 $a 0307
710 2 $a Boston University. $b Biology GRS. $3 3169366
773 0 $t Dissertations Abstracts International $g 81-10B.
790 $a 0017
791 $a Ph.D.
792 $a 2019
793 $a English
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=22619925