Deriving mammalian retina from stem cells has had a large impact on the study of the biology of vision and is called organoid. Compared to in vivo retina, retinal organoids are far less functionally sophisticated in terms of their synapses, connectivity, discrimination between different light stimuli and their electrical action potentials. This project will overcome this functional constraint of retinal organoids by studying electrophysiological events-derived functional maturation of mouse retina during retinal development and then stimulating those events with the help of mathematical models in order to induce the same functionality in mouse and human retinal organoids. NeuFRO will achieve a resonance in the field by generating retinal organoids with the neuronal connectivity and the natural diversity of functions using interdisciplinary fields including electrophysiology, developmental biology, and computationally-derived electrical stimulation. Initially, I will create a holistic roadmap of the electrical features of immature mouse retina during development that shows self-organization through electrophysiology. With milli- to nanometer imaging precision, electrical activities derived the circuit formation will be spatiotemporally documented. Then I will decode this space-time code of intrinsic electrical patterns and neuronal connectivity using an ambitious strategy incorporating Hodgkin-Huxley and linear-nonlinear models. Next, such electrical response models will be applied to immature retinal organoids (mouse and human) by an innovative ‘sandwich’ electrophysiology technique during the development in vitro. With this approach, I will induce naturalistic electrical features in the retinal organoid, allowing the functional neurons to wire and fire appropriately into retinal organoids, particularly visual circuits. This ground-breaking approach will advance techniques for generating functional human retina.

With ever-increasing complexity of novel health technologies, Health Technology Assessment (HTA) methodologies have been evolving rapidly. However, there is now a lack of harmonization on the methodological needs of HTA bodies against the varied methodologies and tools. There is a need for a solution that allows for continuous dialogue between HTA bodies and academia, a solid, unified base for implementation of fit-for-purpose methodologies and long-term upskilling on HTA expertise. SUSTAIN-HTA aims to upskill the pan-European HTA body workforce and harmonise HTA expertise via a robust education and training framework that ensures continuous uptake of novel, need-based HTA methodologies. Aligned to the methodological developments as part of the new EU HTA regulation, the project will set up a mechanism for dialogues and interaction between HTA bodies and academia to regularly assess HTA-bodies’ needs in parallel with a methods observatory that ensures up-to-date knowledge of latest HTA methods. Prioritized methods will be piloted within HTA bodies and, after endorsement, implementation will be supported by a harmonized training and education framework that will be established to upskill the HTA experts. A long-term dissemination and communication structure among all stakeholders will be established to guarantee a feedback loop between HTA needs, methods assessment and associated training needs. Via the collaboration of 5 universities, 7 HTA bodies, 2 SMEs and one non-profit organization, SUSTAIN-HTA brings together extensive experience in (coordinating) previous European funded HTA-related projects including HTx, EHDEN, COMED and GetReEal. With this, SUSTAIN-HTA has the background for establishing sustainable business models that ensures continuity of project outcomes and activities in years beyond the project. SUSTAIN-HTA will support European leadership in the HTA field reach HTA bodies across at least 15 European countries with hundreds of people upskilled.

Transplantation of autologous split-thickness skin -the epidermis with a tiny layer of dermis- remains the golden standard for various skin wounds like burns and large trauma. This treatment, however, comes with a number of serious drawbacks, including pain, mobility-limiting contractures and disfiguring scars. The SkinTERM consortium will address wound healing in a completely different way, recapitulating (certain aspects of) skin embryonic development in adults, and aiming for regeneration rather than repair. Skin organogenesis will be induced by key elements taken from the extracellular matrix of foetal and non-scarring species and by employing (stem) cells from relevant cellular origins. The starting point for the study is the remarkable capability of early foetal skin and skin from the spiny mouse (Acomys) to heal perfectly without scars/ contraction and with appendices such as hair follicles. Novel biomaterials and skin substitutes will be developed and evaluated. In order to effectively embrace this new approach, the PhD students need to have knowledge in key elements of basic science, regenerative medicine and biomaterial sciences. As translation to medical devices and especially advanced therapy medicinal products is currently too limited, we will give the PhD students a solid theoretical and practical foundation on topics like regulatory affairs, GMP and GCP, as well as secondments in industry. Driven by both the enthusiasm to gain basic scientific insights and the need for efficacious and innovative therapies, the students will acquire expertise through cutting edge scientific projects and will be trained by leading experts in all required skills to further develop their scientific findings into real life-science products. The SkinTERM program will thus create a new generation of entrepreneurial, multidisciplinary and inter-sectorially trained scientists with excellent career perspectives in either academia, industry or government.

In 2022, the World Health Organization (WHO) recommended bedaquiline (BDQ)-based, all-oral regimens including pretomanid (Pa), linezolid (L), and moxifloxacin (M) (BPaLM), lasting 6-9 months However, BDQ-resistance is rising dramatically and threatening these advancements. Mozambique has reported BDQ resistance in 28% of MDR-TB isolates in 2024, up from 3% in 2016 and at 10% in South Africa (Ndjeka N, personal communication). Spread of BDQ-R TB must be slowed by antibiotic stewardship through more rapid, accurate, and near-patient diagnostics, and optimized management; until new treatment options with drugs that have no pre-existing resistance or are able to overcome small shifts in MIC will be available. The proposed EX-DR TB project includes diagnostic capacity strengthening, adapting treatment recommendations, and a trial of two new regimens composed of new drugs. The EDCTP EX-DR TB project will: 1. Develop treatment recommendations by a Delphi process with stakeholders - to make use of targeted next generation sequencing (tNGS) that is being rolled out by most national TB programmes - this will yield short-term benefit for patients and NTPs; and will slow the spread of BDQ-resistant bacteria; 2. Rigorously evaluate two treatment regimens composed of new drugs, in a phase 3 clinical trial conducted to the highest regulatory standard – this will be the main focus of EX-DR TB. The trial objective will be to move a regimen towards regulatory approval by FDA and/or EMA, and WHO if supported by results. Thus, EX-DR will create the tools for containing the nascent epidemic of BDQ-R TB and make them available to healthcare providers and TB Programmes. EX-DR TB will be embedded in a larger coalition of funders and partners focused on implementing and evaluating diagnostics and performing the trial beyond of the EDCTP funded area.

Ciliopathies are a large group of rare and severe genetic diseases caused by dysfunction of the primary cilium, a microtubule-based cell surface antenna that controls key signaling output required during development and tissue homeostasis. Cilium dysfunction leads to complex disorders with high genetic heterogeneity and overlapping phenotypes. Despite the broad clinical spectrum, chronic kidney disease (CKD) leading to end stage kidney disease (ESKD) is a common cause of morbidity across ciliopathies. Currently, the only available standard of care for CKD is based on dialysis and transplantation. Renal ciliopathies represent a main cause of ESKD during childhood and despite the identification of more than 40 causative genes, it remains difficult to predict the severity of the disease as well as the risk of appearance (if not present at diagnosis) and the rate of progression of renal failure. TheRaCil therefore aims: (1) to improve diagnosis and prognosis of at risk pediatric renal ciliopathy patients, and (2) to implement therapeutic approaches aimed at targeting shared pathological pathways, at modifying mRNA targets of the causative or modifier genes by antisense oligonucleotides and by the repurposing of available molecules. These goals will be achieved through the federation of our unique databases of pediatric renal ciliopathies cases available across Europe, which will allow a better stratification of patients, the identification of modifier genes and markers of disease progression. Bioinformatics approaches will be used to integrate patients’ biological and genetic data as well as multi-omics and functional analyses from patients samples and preclinical models. These analyses should lead to the identification of shared targetable pathological pathways as well as of patients eligible for the identified new therapeutic approaches which will be evaluated in robust preclinical models.