Investigation of ER Stress in Respiratory Diseases with in Vitro and in Silico Models

Reijer, Jessica

Investigation of ER Stress in Respiratory Diseases with in Vitro and in Silico Models

dc.contributor.author	Reijer, Jessica
dc.contributor.department	C halmers tekniska högskola / Institutionen för biologi och bioteknik	sv
dc.contributor.examiner	Molin, Mikael
dc.contributor.supervisor	Björhall, Karin
dc.date.accessioned	2022-07-01T12:06:16Z
dc.date.available	2022-07-01T12:06:16Z
dc.date.issued	2022	sv
dc.date.submitted	2022
dc.description.abstract	Chronic respiratory diseases are amongst the most common causes of death worldwide. Two of these are chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). COPD is the third leading cause of death worldwide and characterized by irreversible respiratory airflow limitations, with cigarette smoke as one of the most common causes of disease. IPF is characterized by irreversible scarring of the distal lung and often advances into respiratory failure and death within five years of diagnosis. Endoplasmic reticulum (ER) stress has been observed in these respiratory diseases. The aim of this project was to investigate ER stress and the unfolded protein response (UPR) with in vitro and in silico models. The in vitro models included induction of UPR in primary human bronchial epithelial cells (HBECs) by exposure to well characterized ER stress inducers, tunicamycin and thapsigargin, as well as stimuli associated with chronic respiratory disease, H2O2 and cigarette smoke extract. Gene and protein readouts of the UPR pathway, that are characterized markers used to monitor ER stress and UPR, were established and cell viability examined. Gene expressions of for example BiP, CHOP, spliced XBP1 and PPP1R15A and protein expressions of eIF2α, phospho-eIF2α, BiP and ATF6 were induced in HBECs after exposure to the stimuli used. In the in silico model, an UPR gene signature was investigated in single cell RNA sequencing (scRNA-seq) datasets from patients with IPF and COPD, to link epithelial cell type specific transcriptomic markers of UPR to the diseases and investigate the chances in UPR response of different epithelial cell subtypes at gene expression level. Epithelial club cells and aberrant basaloid cells were the most abundant cell subtypes found in IPF and with the highest up-regulation of UPR. In COPD, UPR genes were mostly down-regulated across epithelial cell subtypes. This project was performed at AstraZeneca in the Bioscience COPD IPF Department within the Early Respiratory and Immunology R&D unit located in Gothenburg, Sweden.	sv
dc.identifier.coursecode	BBTX03	sv
dc.identifier.uri	https://hdl.handle.net/20.500.12380/305014
dc.language.iso	eng	sv
dc.setspec.uppsok	LifeEarthScience
dc.subject	COPD	sv
dc.subject	IPF	sv
dc.subject	ER stress	sv
dc.subject	Unfolded protein response	sv
dc.subject	in vitro	sv
dc.subject	in silico	sv
dc.subject	human bronchial epithelial cells	sv
dc.subject	qPCR	sv
dc.subject	Western blot	sv
dc.subject	scRNA-seq	sv
dc.title	Investigation of ER Stress in Respiratory Diseases with in Vitro and in Silico Models	sv
dc.type.degree	Examensarbete för masterexamen	sv
dc.type.uppsok	H
local.programme	Biotechnology (MPBIO), MSc

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