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

Linked to FindBook

Google Book

Amazon

博客來

Developing Analytical Tools to Investigate the Role of Translation in Homeostasis and Disease.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Developing Analytical Tools to Investigate the Role of Translation in Homeostasis and Disease./
Author:	Oertlin, Christian.
Description:	1 online resource (98 pages)
Notes:	Source: Dissertations Abstracts International, Volume: 82-11, Section: B.
Contained By:	Dissertations Abstracts International82-11B.
Subject:	Oncology. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=28518571click for full text (PQDT)
ISBN:	9798728224433

Developing Analytical Tools to Investigate the Role of Translation in Homeostasis and Disease.
Oertlin, Christian.

Developing Analytical Tools to Investigate the Role of Translation in Homeostasis and Disease. - 1 online resource (98 pages)

Source: Dissertations Abstracts International, Volume: 82-11, Section: B.

Thesis (Ph.D.)--Karolinska Institutet (Sweden), 2021.

Includes bibliographical references

Transcriptome-wide studies of translation efficiencies are required to improve understanding of translational regulation and its role in homeostatic mechanisms. In Study 1, we developed an algorithm for analysis of translation efficiency, called anota2seq. We show that anota2seq outperforms current methodologies and, due to its unique analytical approach, it is the only method to statistically distinguish important modes for regulation of gene expression, i.e translation and translational buffering.Pancreatic cancer is a lethal malignancy with very limited treatment options. In Study 2, we evaluate the impact of using an eIF4A inhibitor, CR-31, on mRNA translation in pancreatic cancer. eIF4A is a component of the eIF4F translation initiation complex. We show that inhibiting eIF4A in murine and human pancreatic ductal adenocarcinoma (PDAC) models induces an energy crisis by impacting translation of mRNAs related to oxidative phosphorylation and glycolysis. This leads to the shift of metabolic dependency of PDACs towards reductive glutamine metabolism. Exploiting the dependence on reductive glutamine metabolism using a combined treatment of eIF4A and glutaminase inhibitors revealed an exciting therapeutic treatment strategy for PDAC that did not affect healthy cells.In Study 3, we investigated the effects of insulin on gene expression in malignant and non-malignant cells. This revealed that malignant cells modulate total mRNA levels differently in response to insulin compared to non-malignant cells, whereas in both translation was dependent on mammalian/mechanistic target of rapamycin (mTOR). However, mTOR inhibition during insulin stimulation in malignant cells lead to translational offsetting of alterations in total mRNA levels. Comparing the effects of mTOR inhibition in malignant cells to that of hypoxia in stem cells revealed that these vastly different cell types share the ability to translationally offset mRNAs.Collectively, these studies improved analysis of translational efficiencies and contributed to advanced understanding of the role of translational dysregulation in cancer.

Electronic reproduction.
Ann Arbor, Mich. :
ProQuest,
2023

Mode of access: World Wide Web

ISBN: 9798728224433Subjects--Topical Terms:

751006
Oncology.
Subjects--Index Terms:

Insulin-like growth factorsIndex Terms--Genre/Form:

542853
Electronic books.

Developing Analytical Tools to Investigate the Role of Translation in Homeostasis and Disease.
LDR:03564nmm a2200397K 4500 001 2358653
005 20230824071936.5
006 m o d
007 cr mn ---uuuuu
008 241011s2021 xx obm 000 0 eng d
020 $a 9798728224433
035 $a (MiAaPQ)AAI28518571
035 $a (MiAaPQ)Karolinska_1061647534
035 $a AAI28518571
040 $a MiAaPQ $b eng $c MiAaPQ $d NTU
100 1 $a Oertlin, Christian. $3 3699193
245 1 0 $a Developing Analytical Tools to Investigate the Role of Translation in Homeostasis and Disease.
264 0 $c 2021
300 $a 1 online resource (98 pages)
336 $a text $b txt $2 rdacontent
337 $a computer $b c $2 rdamedia
338 $a online resource $b cr $2 rdacarrier
500 $a Source: Dissertations Abstracts International, Volume: 82-11, Section: B.
500 $a Advisor: Larsson, Ola; Topisirovic, Ivan.
502 $a Thesis (Ph.D.)--Karolinska Institutet (Sweden), 2021.
504 $a Includes bibliographical references
520 $a Transcriptome-wide studies of translation efficiencies are required to improve understanding of translational regulation and its role in homeostatic mechanisms. In Study 1, we developed an algorithm for analysis of translation efficiency, called anota2seq. We show that anota2seq outperforms current methodologies and, due to its unique analytical approach, it is the only method to statistically distinguish important modes for regulation of gene expression, i.e translation and translational buffering.Pancreatic cancer is a lethal malignancy with very limited treatment options. In Study 2, we evaluate the impact of using an eIF4A inhibitor, CR-31, on mRNA translation in pancreatic cancer. eIF4A is a component of the eIF4F translation initiation complex. We show that inhibiting eIF4A in murine and human pancreatic ductal adenocarcinoma (PDAC) models induces an energy crisis by impacting translation of mRNAs related to oxidative phosphorylation and glycolysis. This leads to the shift of metabolic dependency of PDACs towards reductive glutamine metabolism. Exploiting the dependence on reductive glutamine metabolism using a combined treatment of eIF4A and glutaminase inhibitors revealed an exciting therapeutic treatment strategy for PDAC that did not affect healthy cells.In Study 3, we investigated the effects of insulin on gene expression in malignant and non-malignant cells. This revealed that malignant cells modulate total mRNA levels differently in response to insulin compared to non-malignant cells, whereas in both translation was dependent on mammalian/mechanistic target of rapamycin (mTOR). However, mTOR inhibition during insulin stimulation in malignant cells lead to translational offsetting of alterations in total mRNA levels. Comparing the effects of mTOR inhibition in malignant cells to that of hypoxia in stem cells revealed that these vastly different cell types share the ability to translationally offset mRNAs.Collectively, these studies improved analysis of translational efficiencies and contributed to advanced understanding of the role of translational dysregulation in cancer.
533 $a Electronic reproduction. $b Ann Arbor, Mich. : $c ProQuest, $d 2023
538 $a Mode of access: World Wide Web
650 4 $a Oncology. $3 751006
650 4 $a Pathology. $3 643180
650 4 $a Endocrinology. $3 610914
653 $a Insulin-like growth factors
653 $a Vascular endothelial growth factor
653 $a DNA damage
653 $a Hypoxia
655 7 $a Electronic books. $2 lcsh $3 542853
690 $a 0992
690 $a 0409
690 $a 0571
710 2 $a ProQuest Information and Learning Co. $3 783688
710 2 $a Karolinska Institutet (Sweden). $3 3557748
773 0 $t Dissertations Abstracts International $g 82-11B.
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=28518571 $z click for full text (PQDT)