The ImAge-D consortium brings together expert groups from the Norway, Germany, Belgium, Sweden, Poland, Portugal, France and Australia that aim to understand the key changes that arise during ageing and its associated loss of function in the vascular and lymphatic endothelium of different organ vessel beds.

The endothelium is ubiquitous throughout the body lining all blood / lymph vessels of all organs and age-related loss of its function will inevitably affect organ physiology, which led to the “vascular theory of ageing”. Circulating blood interacts with the vascular endothelium of all vessel beds and the “transcriptomic” age of blood correlates better than chronological age with risk factors for cardiometabolic disease and death including cholesterol levels, body mass index, blood pressure and fasting glucose. This would suggest that the interactions of blood and ultimately lymph with the endothelium, and vice versa, dictate ageing, and at the very least would act as very useful “canary in the coal mine”. There is also an age-related decline in the hematopoietic stem cell (HSC) niche in the bone marrow, the body’s blood cell “factory”. HSC niches are – necessarily – closely associated with bone marrow endothelium. Trillions of nascent blood cells enter the circulation daily via this vascular bed, and in ageing the bone marrow microcirculation deteriorates, a process that can be mimicked by surgical denervation in the bone marrow of young mice. The ubiquitous endothelium thus represents a potential novel diagnostic / therapeutic target for the reversal of age-related disorders at multiple levels in multiple organs - improvements to endothelial health will likely improve the systemic health of the elderly. By way of explanation, recent findings suggest that age-related effects on liver sinusoidal endothelium can likely be reversed. While many of that has been shown using older electron microscopic imaging methods, newer optical based methods are rapidly enhancing our ability to study liver endothelium, and ImAge-D will extend the use of these methods to study other endothelial beds than liver.

This project will thus enable a new generation of scientists to explore these new dimensions in endothelium using new optical methods, and place the human (lymph-)endothelium in a central role in modern medicine. Our ambitious goal is that young scientists in this consortium will gain skills and expertise to understand the endothelium at entirely new and unexpected levels. This entails how endothelial behaviour changes with disease / ageing, and how to reverse such degenerative changes by developing drugs / therapies that target ECs in e.g. Alzheimer’s Disease, age-related diseases, vascular diseases and infectious diseases.

This is one of ten PhD positions that are offered in ImAge-D.

ImAgE-D will train a new generation of Doctoral Candidates (DCs) in the development and application of newly developed high speed and high-resolution imaging tools in biomedical research. The ten DCs will be cross-pollinated with concepts and skills in physics and biomedicine, in particular in super-resolution imaging, analytical image reconstruction, and spatial transcriptomics methods. These skills will be applied to reveal for the first time the functionality and morphology (below the diffraction limit of light) of living endothelial cells (EC) that present the main barrier between the blood / lymph and all organs and tissues, and how these vital cells change with ageing. We will employ 10 researchers to address these scientific challenges by performing research in academic and industrial groups, and by doing so receive exhaustive training across relevant disciplines and sectors.

This job offer will start in January 2024, and the others at a later moment, for which ads will follow.

DC6: High speed, super-resolved imaging of nanoscale endothelial cell interactions in-situ and in-vivo

HOST: Biomolecular Imaging Research Group, Bielefeld University, Bielefeld, Germany

SUPERVISOR: Prof. Dr. Thomas Huser (thomas.huser@physik.uni-bielefeld.de)

DURATION: 36 months, starting January 2024

PROFILE: master’s degree in physics, engineering, or (bio)medical sciences. Experience in optic, optics design, super-resolution microsocopy, instrument control, programming and electronics

DESCRIPTION: The project involves the development of novel, fast and multicolor super-resolution imaging approaches based on structured illumination microscopy. The microscope will then be applied for the visualisation of nanostructures in cleared or living organ cultures and behaviour of endothelial cells in response to various challenges will be analysed at the nanoscale, in particular the changes in the vascular niche after drug and genetic challenges and their impact on endothelial function and development will be followed across the scales.

Research visits are planned to UiT (Norway, supervisor Sørensen, 2 months), INL(Portugal, supervisor de Beule, 1 month) and University of Münster (Germany, supervisor Kiefer, 2 months).