Master Thesis

Chronic lung diseases such as Idiopathic pulmonary fibrosis (IPF) are the third leading cause of death worldwide. IPF is a chronic, progressive, irreversible disease no curative treatment. Although IPF pathogenesis is not fully understood yet, it has been proposed that an abnormal wound healing process after repetitive insults to the epithelium and orchestrated inflammatory responses compromise the regenerative potential of the lung, thereby promoting fibrotic changes. Released adenosine triphosphate (ATP) during inflammatory insults acts as a danger signal to promote immune cell activation and mobilization to the site of injury. CD73 catabolizes adenosine monophosphate to free adenosine which signals via its four cognate receptors in target cells, such as immune, epithelial, endothelial and stroma (fibroblasts, myofibroblasts) cells.

Adenosine levels are significantly elevated in pulmonary fibrosis due to higher CD73 activity in the lungs and cause disease exacerbation. Increased adenosine levels associate with higher pro-inflammatory cytokine and pro-fibrotic molecule levels. Moreover, fibroblasts and smooth muscle cells are activated and cause pulmonary arterial hypertension, whereas alveolar epithelial cells oversecrete fibronectin upon A2BAR triggering.

However, the potential of adenosine signaling inhibition as a therapeutic target in pulmonary fibrosis remains to be clarified. We will employ an innovative, unbiased approach to critically assess the underlying cell-specific molecular changes in an adenosine signaling perturbation. We hypothesize that CD73 plays a pivotal role in pulmonary fibrosis. We will combine the human precision cut lung slices (PCLS) ex vivo system with single-cell genomics to elucidate the effects of adenosine signaling inhibition with an antagonistic antibody. To provide a novel insight into the role by which CD73 acts in the context of chronic fibrotic lung disease, we offer a HiWi/Master thesis position in the lab of Dr. Theodore Kapellos (https://www.helmholtz-munich.de/en/lhi/research-groups/kapellos-lab). The successful candidate will:

1. coordinate sample collection and experimental design with the team
2. use the PCLS system and lead the ex vivo experiments
3. perform single-cell RNA sequencing experiments in collaboration with the team

Qualifications:

• Enthusiasm and willingness to work in an interdisciplinary group consisting of basic scientists, clinicians and bioinformaticians
• Proficiency in written and spoken English
• Excellent interpersonal skills
• Ability to work independently and exhibition of good time management skills

Will be considered a plus:

• Previous exposure to flow cytometry and/or human cell culture

To express interest for this position, send one copy of your up-to-date CV and a motivation letter
to Dr. Kapellos (theodoros.kapellos@helmholtz-munich.de).