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Master Thesis in Research Group “Immunopathology of COPD” at the Institute of Lung Biology and Diseases, Helmholtz Zentrum München

Immunometabolic regulation of disease pathogenesis in COPD

06.09.2021

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disorder characterized by progressive airflow limitation and is composed of emphysema and chronic bronchitis. Inflammation, which may be caused by environmental exposures like cigarette smoke or pollution, is a main pathogenic factor in the development of COPD (Conlon et al. 2020, Nature). Today, there is an increasing prevalence of chronic inflammatory conditions that appear to be a direct consequence of modern lifestyle and, in particular, nutritional state and overweight exacerbated by the Western diet (WD). WD causes immune cell reprogramming and drives long-lasting changes in myeloid cell response to innate immune stimuli in bone marrow and reprogramming in monocytes. A deep understanding of the contribution of WD to chronic inflammation by the activation of immune cells is required for effective therapeutic and preventive strategies.

What will you be working on?

We hypothesize that high fat high sugar (HFHS) a WD diet alters the epigenetic state of cells that are contributing to the lung microenvironment, and altered epigenetic memory of cells especially reactive immune cells induces susceptibility to COPD pathogenesis. The molecular mechanisms underlying how they contribute to disease development and which factors are regulating their heightened inflammatory state will be identified.

What techniques will you use?

To understand how altered metabolic state results in persistent inflammatory responses in the lung you will analyse lung samples obtained from animal experiments and cell culture of lung epithelial cells and immune cells exposed to a variety of metabolic stimuli. Conventional molecular biological methods (Western blotting, qPCR, immunohistochemistry staining) will be performed frequently. Moreover, more specialized methods (Flow Cytometry analysis of intracellular and surface stainings and fluorescence microscopy) will be also utilized. This project offers a possibility to learn and understand the molecular mechanisms underlying how the Western diet-driven metabolic dysregulation induces susceptibility in COPD.

Contact Persons
Dr. Yildirim: oender.yildirim@helmholtz-muenchen.de
Dr. Conlon: thomas.conlon@helmholtz-muenchen.de