PROJECT INFORMATION
Host institution: Eberhard Karls University Tübingen
Country: Germany
Supervisory team: Prof. Peter Loskill (PhD promoter, Eberhard Karls University Tübingen), Prof. Stephen Hart (University College London)
PROJECT DESCRIPTON
The objectives are:
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Develop a human-relevant in vitro model for studying lung IRI, to deepen our understanding of the disease and to aid in the development of safe and effective genetic engineering strategies as therapeutic interventions
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To dissect the mechanism of pathogenesis on-chip by precisely controlling oxygen kinetics
Organ-on-a-Chip (OoC) technology is an innovative approach that combines microfabrication techniques with cell culture systems to create microscale fluidic devices that closely replicate human (patho)physiology in a miniature manner, which in particular for an organ as big as the lung, is a key economic benefit. A key feature of these in vitro models is the perfusion through microchannels that mimic vasculature, allowing for the continuous delivery and removal of molecules and cells. To gain a deeper understanding of the pathophysiology of lung IRI, a complex in vitro model based on OoC technology will be developed in the project. Given that the pulmonary endothelium is the primary target of inflammatory IRI, human lung microvascular endothelial cells will be integrated into a microvasculature-like channel, where they will be exposed to physiological shear stress generated by the perfusing media. Additionally the model will include fibroblasts and tissue-resident macrophages as well as circulating neutrophils, allowing for the investigation of the inflammatory response of the innate immune system. Oxygen sensors, integrated into the tissue compartment, will allow in situ monitoring of oxygen concentration. Finally, the model will be exposed to gene therapy approaches from partners in the consortium.
Enrolment in Doctoral School: Eberhard Karls University Tübingen
Planned secondments:
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KU Leuven, Belgium: gene therapeutic agents to modulate IRI (months 11, 34)
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Astra Zeneca, Sweden: Integration of On-chip model in pharmaceutical workflow (month 12)
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UCL, UK: Comparing LNP siRNA silencing of IRI related genes (month 30)
DESIRABLE ESSENTIAL REQUIREMENTS
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You hold a Master’s degree (no PhD) in bioengineering, biomedical sciences, biotechnology, or a related field
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You are passionate about life sciences and engineering, and want to achieve a PhD degree on the topic described in the description above
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You are ambitious, well organized and have excellent communication skills
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You are proficient in English both spoken and written
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You have a solutions-oriented mindset that thrives in a multidisciplinary team
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You have the ability to work independently and have a critical mindset
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You are an enthusiastic and motivated person, eager to participate in network-wide training events, international travel and public awareness activities
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Willingness to travel
SKILLS AND EXPERTISE
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Expertise in either microfabrication and microfluidics or immunology and cell biology
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Knowledge about in vitro models, in particular Organ-on-Chip technology
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Experience with working in interdisciplinary environments.