Aortic aneurysm rupture or dissection is mostly lethal, with an outside-of-hospital mortality rate of 80%. Therefore, timely diagnosis and preventive strategies are urgently needed. About 20% of aortic aneurysms develop in the ascending part of the aorta and is caused by genetic defects (e.g. Marfan) or more complex disease processes, influenced by classic risk factors such as high blood pressure.

The mechanical stability of the aortic wall is governed by its matrix components (e.g. elastin, collagen) as well as regulatory actions of vascular cells (e.g. smooth muscle cells [SMC], endothelial cells [EC]). The biomechanical loading of the aorta is primarily governed by transmural pressure, which determines wall stress given local geometry and tissue properties. Steady-state and pulsatile wall stress have been identified as ‘mechanobiological’ factors that modulate SMC phenotype and function. In addition, local blood flow determines wall shear stress, which is known to modulate EC-mediated regulation of SMC active tension. Taken together, these biomechanical and mechanobiological interactions between aortic wall SMCs and matrix components are of crucial importance in the development of aneurysmatic complications. It is not yet known which of these interactions determine the variation in pathology between clinical patients. Such understanding is essential to develop well-targeted preventive and surgical strategies.

The aim of this PhD-project is to develop a conceptual and computational model of SMC-matrix biomechanical and mechanobiological interactions, informed by in vivo and ex vivo measurements in patients. The project will involve:

I.     Development of in vivo methods (video, ultrasound) to characterise ascending aortic           hemodynamics and tissue properties,

II.   Development of a computational modelling approach (continuum mechanics, fluid-structure interaction) to (1) integrate and interpret measured data and (2) refine hypotheses,

III.  Application of these approaches – in conjunction with patient-derived tissue and SMC        analyses – to identify and characterise key drivers of ascending aortic aneurysm.

As a candidate you should bring excellent engineering skills, with experience in biomechanical modelling and signal processing methods, as well as demonstrable affinity with: (cell) biology, biological materials, surgery and clinical medicine.

This position offers a dynamic and challenging multi-disciplinary environment, with expert supervision and high-tech infrastructure, in a top-quality university hospital.

The preferred starting date for this position is September 1, 2019.

Type contract: 4 years

Fixed-term contract: 4 jaar,We offer a (in total) 4 year full-time contract as PhD student. At the end of the first year your performance will be reviewed and upon a positive assessment, your contract will be extended for a three-year period.

The terms of employment of Maastricht University are set out in the Collective Labour Agreement of Dutch Universities (CAO). Furthermore, local UM provisions also apply. For more information look at the website https://www.maastrichtuniversity.nl/support/um-employees

Maastricht University

Maastricht University is renowned for its unique, innovative, problem-based learning system, which is characterized by a small-scale and student-oriented approach. Research at UM is characterized by a multidisciplinary and thematic approach, and is concentrated in research institutes and schools. Maastricht University has around 18,000 students and 4,300 employees. Reflecting the university's strong international profile, a fair amount of both students and staff are from abroad. The university hosts 6 faculties: Faculty of Health, Medicine and Life Sciences, Faculty of Law, School of Business and Economics, Faculty of Science and Engineering, Faculty of Arts and Social Sciences, Faculty of Psychology and Neuroscience.

CARIM - School CD

CARIM - School for Cardiovascular Diseases

The Cardiovascular Research Institute Maastricht (CARIM), School for Cardiovascular Diseases, is one of the top institutes for translational cardiovascular research in Europe. It is among the world leaders in the fields of research into vascular and thrombotic disorders and atrial fibrillation as well as translational heart failure research. It has also made important international contributions to molecular imaging in the cardiovascular field.

With an annual budget of approximately 20 mln Euros in 2018, CARIM is one of the largest cardiovascular research institutes in Europe, producing more than 500 scientific articles and approximately 40 PhD dissertations per year. CARIM employs 250 researchers from 13 disciplines, about 100 PhD students and 40 technical and support staff members. 

Over the last ten years, CARIM papers have been published in high-impact journals such as the New England Journal of Medicine, JAMA, Nature Medicine, Nature Cell Biology, Cell Metabolism, Journal of Experimental Medicine, Circulation, Lancet Neurology, and the Journal of the American College of Cardiology. Bibliometric analyses illustrate that CARIM publications have been cited 1.97 times more often than the world average for the cardiovascular field in the period of 2009 until 2012.

CARIM is recognized by the KNAW as a research school and as an international training site for Early Stage Researchers in the framework of the Marie Curie Program.