AstraZeneca is a global, innovation-driven biopharmaceutical business focusing on the commercialization of biologic prescription medicines. This full-time paid internship opportunity is for the summer of 2019. We are seeking candidates who are working towards obtaining a bachelor’s degree in Biology, or other related fields. Objective of the Assignment: Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease which is characterized by airflow obstruction that is only partially reversible. COPD affects>5% of the world’s population and is projected to become the third leading cause of death worldwide by 2030. Although COPD has been extensively studied in animals and in vitro models based on primary human cells, these models lack key attributes of the human COPD. Animal models cannot fully represent the human lung because of species differences and human primary cells are difficult to obtain in sufficient amount for drug screening and disease models. These limitations have prevented our better understanding of lung development, function and disease. A key tool to understanding lung pathophysiology is a reliable and scalable source of functional human cells. The lung is composed of specialized endothelial cells that are critical to the health of organ. In this study we will use human induced pluripotent stem cells (hPSCs) to generate lung microvascular endothelial cells (LMVECs) that will be used in ex vivo model for disease modeling and therapeutic approaches. Primary Duties: We will develop method to differentiate human induced pluripotent stem cells (hPSCs) to lung microvascular endothelial cells. During this differentiation process hPSCs progress through stages of mesoderm to endothelial progenitors that become pure populations of lung microvascular endothelial cells. We will confirm LMVECs phenotype including immunostaining as well as quantitative RT-PCR for characteristic markers such as CD31, VE-cadherin, VEGFR2, RAGE. We will also perform functional tests as permeability, tube formation, Dil-acetylated low-density lipoprotein uptake and chemotaxis assays. LMECs will be tested at each passage and for how long they can maintain LMVECs phenotype. Cells will be compared to primary LMVECs. The culture of human endothelial cells. Isolation of genomic DNA and total RNA and gene expression analysis (quantitative RT-PCR) Protein expression analysis (immunocytochemistry). Histological analyses Required Skills: Tissue/Cell Culture, aseptic techniques, Imaging techniques, ELISA, PCR. |
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