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"PhD on Mechanobiology-based engineering of organotypic blood vessels"

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PhD on Mechanobiology-based engineering of organotypic blood vessels

Blood vessels have a critical role in our health to enable transport of blood throughout the body. There are different types of blood vessels—e.g., arteries, veins, microvessels—each with their unique characteristics and functions. Moreover, different body parts demand specific blood transport requirements, resulting in organ- and tissue-specific vasculature, such as their size, vascular wall composition, blood flow rate, mechanical properties and stresses, hemodynamics, and permeability. Efforts to engineer or regenerate vessels, as well as to vascularize tissues and organ(oid)s, should therefore take these variations into account.

A vital feature shared by all these diverse blood vessels is the presence of endothelial cells (ECs), the specialized cells that line the vessel lumens and are in continuous contact with blood. Similar to blood vessels, it is increasingly recognized that ECs are also heterogeneous; their phenotype and behavior are highly organ specific. However, little is yet known about where, why, and how ECs acquire this specificity, and how permanent or adaptable it is. Recent in vitro experiments have shown that ECs from different tissue origins have distinct capacities to sense and respond to mechanical signals (e.g., stiffness, shear stress), to initiate angiogenesis, and to form luminal vessels. These findings offer clues that can be used to better understand and to exploit organ-specific vascularization.

This PhD project primarily aims to elucidate the mechanobiological influences that drive endothelial organ-specification and phenotype, and to use this knowledge to engineer organ-specific ECs. The obtained insights will be used to explore experimental approaches to control vascularization of engineered tissues and organoids. You will work with human induced pluripotent stem cells, differentiate them towards organ-specific endothelial cells, and develop in vitro approaches and assays to study how this differentiation process can be modulated. These experiments will be complemented with computational simulations of mechanobiology-mediated angiogenesis, to further dissect the contributions of cell signaling and environmental mechanical properties.

The research will be conducted in the Department of Biomedical Engineering at the Eindhoven University of Technology (TU/e) under the supervision of Dr. Nicholas A. Kurniawan and Dr. Tommaso Ristori. Dr. Kurniawan’s research strives to make an impact on healthcare through an improved understanding of cell–matrix physical interactions and (multi)cellular sensing, whereas Dr. Tommaso Ristori’s research focuses on blood vessel formation aimed at inducing physiological vascularization of diseased and engineered tissues. Their teams are respectively embedded within the Soft Tissue Engineering and Mechanobiology (STEM) group headed by Prof. Carlijn V.C. Bouten and the Modelling in Mechanobiology (MMB) group led by Dr. Sandra Loerakker. As a member of these groups, you will have access to the Cell and Tissue Engineering laboratory, a state-of-the-art research infrastructure operating at the international forefront of the engineering of living tissues.

We are looking for enthusiastic and talented candidates to join our growing and ambitious research team. You should have/be: A master’s degree (or an equivalent university degree) in (bio)physics, bioengineering, mechanical engineering, or a related field; Demonstrable experience with cell culture and biological assays; A research-oriented attitude; Ability to work in an interdisciplinary team and effectively communicate scientific ideas, foster collaborations, and a capability for independent thinking; Motivated to develop your teaching skills and coach students; Fluent in spoken and written English (C1 level). Affinity to and experience with computational modeling is a plus.

Fixed-term contract: 4 years. A meaningful job in a dynamic and ambitious university, in an interdisciplinary setting and within an international network. You will work on a beautiful, green campus within walking distance of the central train station. In addition, we offer you: Full-time employment for four years, with an intermediate assessment after nine months. You will spend a minimum of 10% of your four-year employment on teaching tasks, with a maximum of 15% per year of your employment. Salary and benefits (such as a pension scheme, paid pregnancy and maternity leave, partially paid parental leave) in accordance with the Collective Labour Agreement for Dutch Universities, scale P (min. € 3,059 max. € 3,881). A year-end bonus of 8.3% and annual vacation pay of 8%. High-quality training programs and other support to grow into a self-aware, autonomous scientific researcher. At TU/e we challenge you to take charge of your own learning process. An excellent technical infrastructure, on-campus children's day care and sports facilities. An allowance for commuting, working from home and internet costs. A Staff Immigration Team and a tax compensation scheme (the 30% facility) for international candidates.

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