This new research infrastructure will enable researchers to understand how (smart) materials and biological processes behave and function on the molecular level. Combining light and microwaves together with a form of molecular MRI scanning allows for new insights of how molecules move and interact. A central focus is on seeing processes on surfaces of materials, such as catalysts and solar panel materials. These new abilities will be deployed in studies of molecular machines, ‘green’ materials, drug carriers, and ageing-associated diseases.

Surprisingly, control of disorder of proteins plays a crucial role in the physiology of cells. Proteins with intrinsically disordered domains have the capacity to phase separate, resulting in membraneless compartments containing high concentrations of proteins in a liquid- or gel-like state. The nuclear pore complex, the conserved gate to a cell’s nucleus, is the best-studied example of a structure that relies on phase separated, intrinsically disordered proteins (IDPs) for its essential function. IDPs are also prone to aggregation, and amyloid formation of IDPs is often associated with pathology, as observed in neurodegenerative diseases. We know virtually nothing about the mechanisms that ensure that IDPs exist in the proper phase state, but two groups of proteins appear critical—chaperones, preventing aggregation of disease related IDPs, and nuclear transport receptors, whose classical function is to shuttle cargo through the nuclear pore complex. Intriguingly, recent studies show that chaperones impact nuclear transport and, vice versa, that nuclear transport receptors act on disease related IDPs. The central question that we will answer is how nuclear transport receptors and chaperones impact the phase transitions of IDPs in guarding the proteome against aggregation, ensuring proper NPC function, and avoiding pathogenesis. We will address this challenge with a cross-disciplinary consortium of leading experts from the fields of nuclear transport and chaperone-regulated protein quality control. By combining in silico, in vitro and cell biological approaches, we aim to discover the mechanisms that guard IDPs from aggregating, and gain an in-depth understanding of the fundamental principles that control the phase transitions of IDPs. By uncovering how IDPs transform from functionally important in normal physiology to drivers of pathology, our work will create opportunities for the development of treatments targeting diverse aggregation pathologies.

The DARTBAC project will prepare the Netherlands for the time when antibiotics are much less effective in the prevention and eradication of infection due to AntiMicrobial Resistance (AMR). DARTBAC will, from a material perspective, develop new antimicrobial technologies that are not based on antibiotics to target infection prevention and eradication on implant surfaces, in hard tissues and in soft tissues and assess their safety and efficacy in in vitro and in vivo models. In this way, we are unique yet synergistic with most other initiatives that focus on an antibiotics approach. Collectively, we are bridging the entire knowledge-chain regarding development of new material technologies to combat AMR. DARTBAC will develop a new workflow based on AOPs of predictive in vitro and in vivo models to test safety and efficacy of newly developed antimicrobial technology in order to shorten the time to market. DARTBAC will enhance the therapeutic efficacy of current antibiotics by combination therapy and we will develop and validate these technologies so that they can be brought to the market within the project timeframe. Finally, we will maintain awareness of the emerging AMR problem in the Netherlands by informing the general public and HealthCare Practitioners (HCPs). This increased AMR awareness by HCPs, the general public, and healthcare policy makers can speed up acceptance and market introduction of these technologies both nationally and internationally. Moreover, such acceptance will ensure that insurance providers and advisory bodies adopt and reimburse new treatment approaches quicker, thereby accelerating clinical implementation. A successful DARTBAC project with the combination of these goals and objectives can prevent a rise in infection percentage due to AMR, minimize the effect of AMR in the Netherlands, and work towards a Dutch society that is less dependent on antibiotic therapy for infection, prevention, and treatment.

The human body contains more microorganisms than its own cells and may contain more microbial genes than there are stars in observable universe. Thus, these greatly influence human physiology, both in health and disease. Despite their abundance in semen we barely know anything about their influence on fertility of men, the health of the couple, miscarriage rates and even the health of offspring. In the project genetic techniques and nanoscale magnetic resonance imaging (nano-MRI) will be used to unravel which microorganisms are in semen, how they influence sperm cells and the consequences this has for the fertility of men.