Cerebrovascular dysfunction, such as loss of the endothelial transporter lipoprotein receptor-related protein 1 (LRP1), which clears a variety of compounds from the brain, including amyloid beta, is increasingly recognized as a major driver of cognitive decline, increased excitability, epilepsy, and Alzheimer’s disease (AD) pathology. However, how microvascular pathology impacts brain wide networks, including thalamus, cortex, hippocampus and cerebellum, remains largely unknown.

In this PhD project, you will test the overarching hypothesis that endothelial LRP1 loss in mice disrupts brain wide networks, leading to impaired coherence, increased excitability, disturbed sleep patterns, and exacerbated amyloid pathology. Furthermore, you will test whether enhancing cAMP/cGMP signaling with a selective phosphodiesterase-1 (PDE1) inhibitor and applying deep brain stimulation can ameliorate vascular and circuit dysfunction.

Tasks and responsibilities

• complete and defend a PhD thesis within the official appointment duration of four years;
• use multidisciplinary approaches (patch-clamp, optogenetics, mouse behaviour, stereotaxic surgery) to measure/manipulate thalamic circuits and behaviour;
• perform your experiments in a systematic and well controlled manner;
• keep accurate records by thoroughly documenting and organising your work;
• stay on top of the relevant scientific literature;
• discuss your work in our lab meetings, incorporate feedback and give input to others;
• assist in teaching and supervise BSc/MSc students during their research internship;
• participate in the Faculty of Science PhD and Graduate School Neurosciences training programmes.

You will get the opportunity to

• learn a wide variety of experimental and data analysis techniques;
• build a network as part of our (inter)national collaborations;
• present your work at (inter)national meetings;
• continuously hone your academic, professional and personal skills;
• contribute to the science communication and outreach activities of the lab.

You work well independently but are also willing to contribute to team efforts. You are a nice colleague with good communication skills. You use your organizational skills to ensure efficient planning and project management, enabling you to meet deadlines. Your work shows that you pay attention to detail, but you also have eye for the bigger conceptual picture. You draw on your critical thinking and problem-solving skills when needed.

Your experience and profile:

• a recent MSc degree in the neurosciences (or a related area);
• a strong interest in aging biology and Alzheimer’s disease;
• a strong intrinsic motivation and aptitude for fundamental research (reflected by your training record);
• an Art. 9 qualification (or the willingness to become Art. 9 qualified);
• willingness to work with mice;
• willingness to supervise BSc and/or MSc students during their internship;
• fluent in English, both written and spoken.

If you are genuinely excited about this project and are willing and able to learn, then we offer you the environment to do so. However, it will work to your advantage if you already have some (hands-on) experience with one or more of the following: mouse handling, histology analyses, whole-cell patch-clamp or in vivo electrophysiology.

A temporary contract for 38 hours per week for the duration of 4 years (the initial contract will be for a period of 18 months and after satisfactory evaluation it will be extended for a total duration of 4 years). The preferred starting date is 1 January 2027. This should lead to a dissertation (PhD thesis). We will draft an educational plan that includes attendance of courses and (international) meetings. We also expect you to assist in teaching undergraduates and master students.

Your salary will range between €3,204 in the first year to €4,051 gross per month in the last year of employment, based on a fulltime employment (38 hours per week). This sum does not include the 8% holiday pay and the 8.3% end-of-year bonus. A favorable tax agreement, the 30% ruling, may apply to non-Dutch applicants. The Collective Labour Agreement for Dutch Universities (CAO NU) is applicable. Curious about our extensive secondary benefits package? You can read more about it here.