The brain is supplied by a complex and vast vascular network whose interactions are difficult to grasp in their entirety. The neurovascular unit (NVU) was thus introduced and represents the minimal functional unit linking the brain and its vessels. NVU cells interact closely to maintain the integrity of the blood-brain barrier and supply the brain with nutrients. Among these, astrocytes play the key role of mediator between the endothelial cells, supporting the blood flow, and the neurons. The astrocyte-neuron lactate shuttle is an essential communication pathway, and its control is crucial for brain homeostasis and thus brain health. 

The research hypothesis of ANCOM is that the engineering of astrocytes will allow to modulate their communication with neurons in close proximity, cultured in a paper-based NVU model. Engineered astrocytes can thereby be used to influence neurons’ behaviour. Specifically, artificial organelles will be designed to boost the lactate production in the astrocytes. These artificial organelles will be made of silica nanoparticles with lactate dehydrogenase enzyme immobilised in polymer brushes their surfaces and placed in the cytosol of the astrocytes. Due to the boosted lactate release by the astrocytes, a beneficial effect on neurons is hypothesized. In addition, a dynamic in vitro paper-based model of the NVU containing endothelial cells, pericytes, astrocytes and neurons will be established. These NVU model will be used to determine the potential of the artificial organelles in a more realistic environment that also imitates shear stress and the blood-brain-barrier  Although fundamental in nature, the successful outcome of ANCOM is anticipated to be widely applicable from addressing fundamental questions in neuroscience to clinical research following due development, as well as in the private sector to advance drug target identification, development and testing. This multifaceted, interdisciplinary project will allow me to broaden my scientific and leadership skills and consequently kick-start my career as an independent researcher.