Project description
Exploring the impact of uremic toxins on the blood-brain barrier
Chronic kidney disease (CKD) affects over 840 million people worldwide, with its prevalence increasing due to ageing and related conditions, leading to escalating healthcare costs and disease burden. In advanced stages, CKD results in the accumulation of harmful toxins known as protein-bound uremic toxins (PBUTs), which can disrupt the blood-brain barrier (BBB), potentially impairing neurological health. With the support of the Marie Skłodowska-Curie Actions programme, the BBB-UT project aims to develop a multi-organs-on-chip device to unravel the impact of PBUTs on BBB integrity and functionality. The project will focus on kidney-brain axis dysfunction in neurological complications. By creating a microfluidic-based BBB-on-chip model connected to a kidney-on-chip system, the project will provide insights into BBB integrity and PBUTs behaviour, ultimately advancing CKD therapies.
Objective
Chronic kidney disease (CKD) is estimated to affect more than 840 million people worldwide constituting a major global health crisis. Clinically, the number of CKD patients will continue to rise mostly because of the ageing population and the increased prevalence of comorbidities such as diabetes and hypertension. In Europe, around 100,000 million people are affected by it. According to the gloomy predictions, Europe is at risk of a dismal increase of CKD patients as well as costs to healthcare systems. Patients with advanced CKD display a loss of kidney function leading to a blood accumulation of, a.o. protein-bound uremic toxins (PBUTs) that are poorly eliminated by renal replacement therapies. This systemic retention known as the uremic syndrome affects other organs. Indeed, neurologic complications such as blood-brain barrier (BBB) disruption have been reported in CKD patients. The BBB guarantees the exchange between the blood and the brain through a complex cellular organization and a diverse range of transport proteins mediates the movement of endo/exogenous compounds.
I hypothesize that impairment of kidney tubular functionality in CKD causes an alteration of BBB integrity and function. This results in an aberrant BBB pass-through of PBUTs as well as impacts BBB vectorial transport capabilities. This fellowship aims to develop an appropriate multi-organs-on-chip device to accurately describe (i) the impact of PBUTs on BBB integrity and functionality, and (ii) the involvement of kidney-brain axis dysfunction in PBUTs-driven BBB disruption. We will develop a bioprinting-based microfluidic BBB-on-chip to accurately study BBB permeability, architecture, and transport function. This device will be connected to our established proximal tubule-on-chip to form a robust (kidney-brain) multi-organs-on-chip system. This project will pave the way toward the establishment of new and effective CKD therapies, and an expert system for pharmacology studies in a near future.
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- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences basic medicine pharmacology and pharmacy
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Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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(opens in new window) HORIZON-MSCA-2022-PF-01
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3584 CS Utrecht
Netherlands
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