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. Overview/Objective of the Assignment: Human airway diseases such as cystic fibrosis (CF), asthma and chronic obstructive pulmonary disease (COPD) are becoming increasingly prevalent, and mortality from these diseases is rising. One of the major roadblocks in airway disease research is the lack of proper ex vivo models that accurately reflect the alveolar compartment. Importantly, access to lung tissue from patients is limited, and is obtained from individuals that have died, or had their lungs transplanted, which only reflect a snapshot of end-stage disease. Furthermore, animal models of chronic lung disease have limitations that do not reflect human disease. Factors such as high cost and logistical hurdles limit the use of large animal models. Induced pluripotent stem cells (IPSCs), and their differentiation to alveolar epithelial type 2 cells (AE2) , have emerged as a promising new tool for studying the alveolar compartme ex vivo. An ex vivo model that better reflects disease pathophysiology will advance studies in COPD and other chronic lung diseases, to better understand airway epithelial pathobiology and to test potential therapeutics. In this study, we will utilize IPSC derived AE2 cells in a co-culture system with human lung fibroblasts from healty and COPD donors, to develop an alveolar model that closely mimics human physiology and disease. In this study we will look at the role of human lung fibroblasts in the development and maturation of AE2 cells to AE1 cells in reconstructing the alveolar compartment ex vivo. By using lung fibroblasts from both healthy and COPD donors we will examine the role of fibroblasts in alveolar development and regeneration in a disease state. We will use real-time QPCR, confocal imaging, and flow cytometry to examine gene expression profiles, visualize co-culture systems, and quantify cell types contributing to alveolar regeneration. This study will provide valuable information on the role of fibroblasts in alveolar development in both healthy and disease states. Primary Duties: Culturing IPSC derived alveolar epithelial type 2 cells in 3D culture system Co-culture of IPSC derived AE2 cells with human lung fibroblasts Isolation of RNA and gene expression analysis (quantitative RT-PCR) Confocal imaging Flow Cytometry of alveolospheres Required Skills: Tissue/Cell Culture, aseptic techniques, Imaging techniques, ELISA, PCR. |
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