Diabetes remains one of the major risk-factors for development of cardiovascular disease (CVD), but glucose-lowering treatment does not quickly or consistently lower this risk. This remains a poorly understood phenomenon.A possible mechanism through which glucose has a damaging effect on the vasculature might be via the formation of the major dicarbonyl methylglyoxal (MGO). MGO is rapidly formed as a glycolytic intermediate by metabolic conversion of glucose. In turn, MGO rapidly modifies protein residues, forming advanced glycation endproducts (AGEs). We found that these AGEs are higher in rupture-prone plaques. We also found that higher MGO levels are associated with incident CVD in people with diabetes.

In this project, we will address whether MGO directly contribute to vascular dysfunction and CVD, mainly using cell culture experiments and animal experiments. We have developed several experimental set-ups, which the PhD candidate will use to study whether increased MGO levels increase vascular dysfunction in rodents. We will also focus on microvascular diabetic complications. Phenotyping of animal models will be done using state of the art mass-spectrometry, flow cytometry, microscopy, cytokine arrays, and vascular function measurements with contrast ultrasound and the myograph.  When appropriate, we will further validate our analyses with the use of human cohort studies in which MGO levels have been measured. These epidemiological analyses will be supervised by an epidemiologist. The impact, from a clinical point of view, will be that this study will lead to new possibilities for interventions to combat CVD.

A main advantage of obtaining a PhD in our group is that we offer an informal, friendly and very multidisciplinary team, in which biochemists, biologists, physician-scientists, technicians and epidemiologists closely collaborate to translate our research findings into clinical practice. In fact, our group is currently undertaking a small clinical trial to investigate whether an inhibitor of MGO prevents insulin resistance and vascular dysfunction in people with obesity. Our group has access to broad range of analytical techniques, and a well-trained team of technicians to make sure the candidate will feel comfortable working with the techniques available in our lab. Many of the previous studies by our group have been published in leading journals.

To fill the PhD position for this project, we are looking for an enthusiastic candidate with a strong motivation and the ability to proactively tackle the project’s research questions. The candidate should have a background (master degree or equivalent) in biology, biochemistry, health sciences or Medicine and have an outspoken interest in biomedical research. Experience with animal work (small rodents) is a prerequisite and possession of a Laboratory Animal Licence is a clear advantage. Subsequent to the PhD project, there will be the possibility for candidates with a degree in medicine of a residency program in Internal Medicine. 

Dienstverband voor bepaalde tijd: 4 years.

Temporary employment for 4 years.

Your salary would be € 2.222,- gross per month in the first year up to € 2.840,- gross per month in the fourth year according to the PhD-student salary scale.

Each year an evaluation will take place.

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 www.maastrichtuniversity.nl , Support/UM employees/Employment conditions.

CARIM - School for Cardiovascular Diseases

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 22 mln Euros in 2016, CARIM is one of the largest cardiovascular research institutes in Europe, producing more than 550 scientific articles and approximately 45 PhD dissertations per year. CARIM employs 250 researchers from 13 disciplines, about 120 PhD students and 50 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.

 Cardiovascular scientists from around the world join CARIM because it values open communication, close cooperation, high ambitions, good facilities and a critical learning environment.