Renal and cerebral small vessel disease: an inflammatory tangle
This project aims at identifying the sequential relationship between renal and cerebral microvascular dysfunction in hypertension. We hypothesise that a specific panel of pro-inflammatory signals is responsible for the initiation of a pathological cascade, including extracellular matrix and vascular remodelling which occurs concomitantly with capillary rarefaction in kidneys and later in brain. The ESR will work in close collaboration with other ESRs to assess the differential expression of proinflammatory mediators in both kidneys and brain over time and to study the potential involvement of advance glycation end-products (AGEs) in this deleterious signalling
Cerebral and renal tissues from diseased animal models will be studied by advanced 3D imaging and mass spectrometry imaging and correlated to renal and cerebral functional parameters. The sequential relationship between kidney and brain pathology will be assessed at different time points. The 3D architecture (e.g. tortuosity, branching) and density of the microcirculation in brains and kidneys will be studied using tissue clearing technique combined with 2-photon and light sheet microscopies in collaboration with Intelligent Imaging. Furthermore, MSI with integrative molecular histology will allow analysis of microvascular dysfunction in relation to alterations in lipids and metabolites induced by the pro-inflammatory signals. Using this molecular histology approach, we will identify inflammatory/metabolic drivers that systemically affect the microvasculature and accelerate the development of organ damage.
- Qualifications: MSc degree in a biomedical related field; animal FELASA certificate.
- Experience: previous experience in a related field is an asset.
- Knowledge & skills: experience with common molecular techniques; animal work and microscopy.
- Abilities: good English working proficiency (min C1 level).
- Attitude and disposition: Creative and independent thinker; excellent communicator (oral and written); team worker; willing to do secondments abroad (6 months abroad).