Ongoing Horizon Europe projects

Toward consolidation of germplasm and cell reversible drying through knowledge transfer

Call: HORIZON-MSCA-2022-SE-01
Type of Action: HORIZON-TMA-MSCA-SE
Number of participants: 7
Role: Participant

Objective: WhyNotDry will deepen our knowledge on reversible drying in cells and germplasm toward the development of a dry biobanking as an alternative to the current freezing in Liquid Nitrogen (LN). LN is expensive, requires dedicated facilities and power supply, and has a high CO2 footprint. WhyNotDry will achieve its aims through a multidisciplinary, intersectoral, international network of scientists that will: i) Develop a drying/rehydration platform using naturally desiccation-tolerant midge (Polypedilum vanderplanki) Pv11 cell lines; ii) Identify the best combination of naturally occurring xeroprotectants (xero=dry) from desiccation-tolerant insect cell line and the best performing water subtraction platform. iii) To use the best xeroprotectants mix and the drying/rehydration protocol for mammalian cells/germplasm. vi) Develop a prototype for controlled dehydration of microvolumes of cell. The R&I activities leading to these aims will be carried out by knowhow sharing through Staff Exchanges between: 3 EU academies, 2 EU SMEs, 2 international partners (Japan, Thailand). Outcomes of WhyNotDry will be incorporated into a cheap, environmentally friendly, and easy biobanking for biodiversity conservation, assisted reproduction, stem cell/personalized medicine. Successful development of this technology will set the basis for a radically new, ‘green’ biobanking paradigm, simplifying the maintenance and shipping practices in life sciences, with enormous reduction in costs and carbon footprint. Moreover, knowledge generated in WhyNotDry would be applicable to other fields such as agriculture, environmental science, food processing, and the pharmaceutical industry, where elective or enforced (by climate change) drying is dealt with. Finally, WhyNotDry will empower young scientists with transferable skills, ensuring career prospects in academia/industry, and strengthen the international/sectorial network between disciplines, boosting European excellence.

Bench to bedside transition for pharmacological regulation of NRF2 in noncommunicable diseases

Type of action: COST
Action number: CA20121
MoU: 061/21
CSO Approval date: 25/05/2021
Start date: 19/10/2021
End date: 18/10/2025
Role: Management Committee member and Working Group member

Non-communicable diseases (NCDs) such as cancer, diabetes, cardiovascular, neurodegenerative, respiratory or immune diseases, account for 77% of all deaths in Europe and remain the most prevalent and without effective therapy. Networking among multidisciplinary teams that explore disease from a perspective of causative pathomechanisms rather than clinical symptoms is the most appropriate approach to overcome this problem. Such pathomechanisms imply the loss of homeostatic functions leading to the pathologic formation of reactive oxygen species, chronic inflammation, metabolic unbalance and proteinopathy. The transcription factor NRF2 is a master regulator of multiple cytoprotective responses and a key molecular link among many NCDs. It provides a unique strategy for drug development and repurposing that is now starting to be translated to the pharmacological and clinical arena. This Action will build a network of excellence for integrating and spreading the existing knowledge and providing innovative services, drugs and tools related to NRF2-pharmacology, with the final goal of boosting the translation to the European industry sector. To achieve this, the Action has already gathered a wide set of professionals from different disciplines (medical chemistry, pharmacology, clinical research, molecular biology, bioinformatics, etc.) and sectors (universities, research centres, hospitals, biobanks, biotech SMEs and pharma companies, etc.). The Action will expand among COST countries IPCs and NNCs, will actively involve SMEs and ECIs, and will respect gender balance.Thanks to COST tools the Action will boost the career of young researchers, wide participation (especially from ITC countries), and spread excellence.

Generation of human induced pluripotent stem cells from HAPLO-selected cord blood samples

Type of action: COST
Action number: CA21151
MoU: 065/22
CSO Approval date: 27/05/2022
Start date: 11/10/2022
End date: 10/10/2026
Role: Management Committee member and Working Group co-leader

HAPLO-iPS aims to create a collaborative network to provide a framework for hiPSC generation of hiPSC homozygous for frequent HLA haplotypes, compatible with a significant percentage of the population to be used for cell therapy clinical trials and to create a data collection system (REGISTRY) for such lines.
HAPLO-iPS will establish an European-based excellence network on hiPSC-derived cell-based medicines that not only will boost the state-of-the-art of this research field if not will also contribute to Europe worldleadership through the medical, scientific, economic, and social development of Europe and strengthening Europe’s competitiveness capacities. This network includes all the relevant stakeholders: hiPSC generation/banking centres, CB banks that will supply cord blood units; manufacturing centres (GMP complying), immunology experts, chemistry and manufacturing controls, regulatory bodies, National Agencies, and ethics experts. The challenge will be approached essentially by networking with all the stakeholders involved sharing knowledge, standardizing methodology and developing an educational training programme for researchers.
HAPLO-iPS is also promoting the participation of researchers from less research-intensive countries as a significant percentage of the members are from ITC countries. ITC participants will have access to research facilities, training courses, mentoring of ITC young researchers and will participate spreading excellence and widening participation programme. Furthermore, Key leadership positions in the Action Management are reserved to COST ITC.
Overall, this action will pioneer new approaches that will foster the progress of a haplo-selected hiPS generation of therapeutics by the development, implementation and exploitation of a registry with all the information for the benefit of patients.

The role of immunity in tackling Parkinson’s Disease Through a Translational Network

Type of action: COST
Action number: CA21117
MoU: 031/22
CSO Approval date: 27/05/2022
Start date: 20/09/2022
End date: 19/09/2026
Project website: https://immuparknet.eu/about/
Role: Management Committee member and Working Group member

Parkinson’s disease (PD) is a widespread chronic disease affecting 600 000 people in the EU. It has no cure, hence patients rely only on symptomatic treatments. By consequence PD relentlessly results in serious disability, poor quality of life for patients, families and caregivers, causing high individual and societal costs. PD etiology is largely unexplained and several pathogenetic hypotheses have been explored. The role of the immune system has been suggested by important studies, showing significant changes in both central and peripheral immunity. Several approaches exist to target the immune system, thus – would the contribution of immunity in PD be clarified – novel therapeutics could be developed. Currently only few research groups study the role of the immune system in PD; however methodological and technical approaches are highly variable. Moreover, networking and exchange of expertise between groups working on immunity in different pathologies is still underdeveloped, with the consequence that precious advances are not fully exploited or even precluded. The sharing of experiences, also taking advantage of the efforts made in similar neurodegenerative conditions, will provide unprecedented advantages.
IMMUPARKNET focuses on such challenges and aims at establishing an innovative, multi-interdisciplinary Network, fostering exchange of expertise among outstanding experts, from different countries and institutions, involving scientists studying immunity in PD but also immunity in other neurodegenerative diseases. IMMUPARKNET will thus establish a first nucleus of a multidisciplinary ecosystem to fight the fragmentation of efforts and approaches, both in research and clinical practice, for boosting research towards the development of innovative treatments for PD.

Genome Editing to Treat Humans Diseases

Type of action: COST
Action number: CA21113
MoU: 027/22
CSO Approval date: 27/05/2022
Start date: 15/09/2022
End date: 14/09/2026
Project website: https://www.genehumdi.eu/
Role: Management Committee member and Working Group member

Recent advances on genome editing (GE) technologies have opened the possibility of treating diseases through precise modifications of patients’ genomes. Impressive results have been achieved on animal models of several genetic disorders, infectious diseases as well as cancer and several clinical trials are already on going. However, the inadequate integration of the results of academic research into the research development strategy of pharmaceutical companies, the insufficient interest of academic institution in regulatory science and the absence of established standards to well acceptable risk-benefit ratio by regulatory agencies, preclude its general application for treating human diseases. Therefore, the translation of the GE technologies to address public health needs, require a strong collaboration between basic and clinical research, regulatory bodies and the different stake holders involved for each application. There are several networks to improve or analyse GE technologies for different applications,
however, no one cover all the actors involved in gene therapy translation. The principal aim of the GenE-HumDi Action is to bring together pharmaceutical companies, academic institution, science and regulatory agencies, biotechnology firms, patient advocacy association and information technology, in order to tackle knowledge fragmentation with the aim to accelerate the translation of GE technologies to the treatment of human diseases.

Medicine made to measure

Call: MSCA Doctoral Networks 2022 (HORIZON-MSCA-2022-DN-01)
Type of Action: HORIZON-TMA-MSCA-DN
Number of participants: 22
Role: Participant

Objective: Modern medicine seeks to personalize diagnosis and treatment to the needs of individual patients. This need is heightened in particular for those individual patients where no treatments are available – and where current standard treatment development paradigms exclude to generate such. The ultimate goal of Medicine made to Measure (MMM) is to go even beyond the latest genetic medicine approaches, implementing a novel paradigm of treatment development: the field of single patient tailored antisense oligonucleotide (ASO) treatments for patients with nano-rare disease mutations. Specifically, MMM will develop core modules of a novel “out-of-the-box”, but still EMA-advised treatment development path for these patients – from omics-based theranostics, via preclinical target validation to innovative trial methodology and a pioneering ethical framework for individualised genetic therapies. MMM provides a unique opportunity for doctoral candidates to be involved in building – and to receive training – in all core modules needed for tailored ASO treatment in Europe. This new scientific field requires a new generation of open-minded, technology-fluent and applications-oriented experts.

MMM will help educate future drug development and translational experts in adopting and disseminating such a cross-specialty approach. Our idea for this innovative training network is built on our personal experience and understanding of the importance of single patient tailored genetic treatments in the years to come. We propose a consortium of world-leading experts and partners that present with extended experience and relevant know-how in molecular biology, neurology, translational medicine, biochemistry, bioinformatics, philosophy, mathematics, regulatory science and engineering. Thus, MMM provides an exceptional platform to young, ambitious and talented researchers who like to engage in supporting the concept of single patient tailored treatments.

Targeting Circadian Clock Dysfunction in Alzheimer’s Disease

Call: MSCA Doctoral Networks 2021 (HORIZON-MSCA-2021-DN-01)
Type of Action: HORIZON-TMA-MSCA-DN-JD HORIZON TMA MSCA Doctoral Networks – Joint Doctorates
Number of participants: 24
Role: Associated partner

Objective: Recent Nobel Prize-winning discoveries on circadian clock (CC) have laid the foundation for ground-breaking approaches to treat many diseases, including Alzheimer’s disease (AD). AD is a current public health priority. Amplifying the demographic burden of the rising numbers of patients is the low success rate of AD therapies. Given that CC genes regulating memory, sleep, and neurodegeneration have altered expression profiles in AD, CC has recently emerged as a viable therapeutic target for new effective drugs. However, how to develop them remains a fundamental challenge. The “Targeting Circadian Clock Dysfunction in Alzheimer’s Disease” Doctoral Network (TClock4AD) is proposed to create a new generation of researchers able to face such challenge by harnessing neurobiology, medicinal chemistry, pharmaceutical nanotechnology, neuroimmunology, big data, bioinformatics, and entrepreneurship. TClock4AD will exploit unique expertise and advanced technologies at 10 leading universities, 3 research centers, a hospital, 10 non-academic institutions including SMEs, a large pharma company, a Health industry association, and a patient organization across EU, UK, Israel, USA and China. TClock4AD will deliver double degrees to 15 doctoral candidates, with triple-i knowledge/skills, broad vision and a business-oriented mindset. Their research activities will be structured around 5 scientific themes to: (1) develop novel artificial intelligence-, proteolysis targeting chimeras- and multitarget-based strategies for new CC drug candidates (2) develop novel drug delivery nanotechnologies, which take into consideration CC (3) investigate innovative in vitro (stem-cells, 3D cultures) & in vivo (Drosophila), as well as organ-on-chip techniques, for preclinical validation of CC drugs (4) get insight into the molecular mechanisms underlying CC in AD and associated drug response in mice and C. elegans models (5) develop innovative biotech business model and exploitation strategies.

Unveiling the molecular basis of chromatinopathies to delineate innovative therapeutic solutions

Call: MSCA Doctoral Networks 2021 (HORIZON-MSCA-2021-DN-01)
Type of action: HORIZON-TMA-MSCA-DN HORIZON TMA MSCA Doctoral Networks
Number of participants: 14
Role: Associated partner

Objective: Chromatinopathies (CPs) are a group of rare genetic diseases, which share clinical features as well as causal genetic alterations, leading to the inactivation of chromatin regulators involved in gene expression control and 3D chromatin organization. Within the framework of Chrom_Rare, we will focus on a group of clinically well-defined CPs, including Kabuki Syndrome, Charge Syndrome, Rubinstein-Taybi Syndrome and Cornelia de Lange Syndrome. Although the causative genes for these CPs have been identified, the consequences of their inactivation both at the molecular and functional level, have not been defined. The clinical features of CPs vary widely, suggesting that the impact of the haploinsufficiency of the affected chromatin regulators could depend on the epigenetic state and/or interactions with additional genetic and environmental factors. Hence understanding the genetic and epigenetic determinants of CPs represent an immediate medical need, as this will ultimately facilitate reaching the development of new therapeutic approaches. Our main goal is to set-up an intra-sectoral, cross-disciplinary training programme that would prepare the next generation of researchers equipped with advanced theoretical, technical and computational skills to study fundamental aspects of chromatin biology and their impact on CPs. In parallel, Chrom_Rare will devise new strategies to translate the molecular findings into new diagnostic and therapeutic approaches for patients affected by CPs. To enable understanding the molecular basis of chromatinopathies, we aim at developing multiple disease models recapitulating the main clinical features of CPs (WP1), investigating the genetic, epigenetic and topological determinants of CPs (WP2) and uncovering perturbed regulatory circuitries suitable for therapeutic intervention (WP3). Overall Chrom_rare will address unmet socio-economic, medical and scientific needs, for the understanding and possible treatment for CP.

Ongoing H2020 projects

Neurodevelopmental ciliopathies: a multimodel approach from molecular mechanisms to patients
variant interpretation and treatment strategies

Call: JTC2021 – Neurodevelopmental Disorders
Type of research: ERA-NET NEURON (Neurological and Mental Disorders)
Logo: under development
Number of Participants: 6
Role: Partner
Project number: to be confirmed
Project website: https://ndcil.eu/

Objective: Neurodevelopmental abnormalities resulting in life-long disability are a major feature of inherited ciliopathy disorders. Primary cilia are found on most cell surfaces, including neurons, and play key signalling roles during development. However, little is known about ciliary function/dysfunction in the brain, and no curative strategies exist for these disorders. Moreover, several patients carry “variants of unknown significance” (VUS), whose pathogenic impact on disease mechanisms remains unknown. To address these shortfalls, NDCil will focus on four major genes causing the archetypal neurodevelopmental ciliopathy, Joubert Syndrome (JS), and will employ complementary in vitro models (mouse embryonic stem cells, patient-derived induced pluripotent stem cells undergoing 2D and 3D differentiation towards cerebellar neurons and astrocytes) and in vivo models (C elegans, zebrafish) and wide-ranging techniques (CRISPR, proteomics, transcriptomics, live cell imaging, high throughput drug screening) to characterize and compare a wealth of variants (mainly VUS), identified in JS patients. Aims of NDCil are: i) to increase knowledge of cilia in neural development and disease at multiple scales (from the subciliary TZ compartment to neurons, to the whole brain); ii) to correlate specific patients’ mutations with JS mechanisms and improve VUS interpretation; iii) to explore novel therapeutic approaches via drug repurposing strategies. Together, our interdisciplinary consortium of five partners provides a platform for assessing and remedying the effects of specific mutations on neurodevelopment processes, with expected benefits on diagnosis, prognosis and counselling.

Defining (sex and age) cell-specific epigenetic mechanisms underlying Environmental Enrichment/Exercise as non-pharmacological intervention for Alzheimer’s and Huntington’s disease and related potential noninvasive biomarkers

Call: Understanding the mechanisms for non-pharmacological interventions (2022)
Type of research: ERA-NET JPND (EU Joint Programme – Neurodegenerative Disease Research)
Logo: under development
Number of Participants: 8
Role: Partner
Project number: to be confirmed
Project website: under development

Objective: Aerobic exercise or cognitive training, as well as the combination of both (referred to as environmental enrichment, EE) can enhance synaptic plasticity, improve memory function and ameliorate disease phenotypes in animal model for age-associated neurodegenerative diseases, such as Alzheimer’s disease (AD) and Huntington’s disease (HD). Similar observations have been made in humans, in both healthy individuals and patients and the applicants have contributed to both lines of research. Given that epigenetic regulations are central to the integration between environmental and genetic factors, we hypothesize that they are critical in conveying environmental therapies into beneficial effects. Epigenetic changes associated with AD and HD have been extensively characterized in mouse models and in human patients’ brains, including by the applicants. However, the role of epigenetic mechanisms in beneficial effects of environmental enrichment and exercise has remained largely unexplored. Particularly, the role of the non-coding RNAs could represent excellent biomarkers of environmental and exercise impact on the epigenome, since they may be detected in blood samples or Extracellular Vesicle (EV)-enriched fractions. In this project, we propose to elucidate the mechanisms that underlie EE and Exercise as a non-pharmacological intervention towards age-associated dementia and test specifically the hypothesis that epigenetic changes to brain cells play a key role. In a first aim, AD and HD mouse models undergoing EE and/or Exercise will be used to lead cell-type specific multi-omics (genome-wide analyses of chromatin and transcriptional modifications) and build computational regulatory models in the context of chromatin dynamics in two brain regions affected by the diseases, further identifying non-coding (nc)RNAs as biomarker candidates for efficient therapy. Behavior and brain MRI will attest for beneficial effects of such stimulation. Epi-editing approaches will bring mechanistic insights. The second aim is designed to translate our data to human searching for a noninvasive candidate ncRNA biomarkers isolated from blood samples of AD and HD patients (collaboration with neurologists), that could be relevant of successful EE and/or exercise strategy. Further, enrichment of ncRNA biomarker candidates will be assessed in specific circulating extracellular vesicles from the plasma. Lastly, selected RNA markers will be tested for their ability to reproduce identified epigenomic changes in human-derived cellular systems and further validated in new cohorts of patients. By providing insights in molecular/cellular, sex and age-dependent mechanisms underlying non-pharmacological interventions such as EE/Exercise in main brain regions affected by AD and HD, our data will offer novel opportunities for medicine personalization. Defining the specific epigenetic response to EE/Exercise and a mean for its biological tracing will bring further opportunities to define new therapeutic strategies or use combinatorial therapeutic strategies supporting non-pharmacological ones (epi-drugs or RNA-based therapeutics).

ElectroMechanoActive Polymer-based Scaffolds for Heart-on-Chip

H2020-NMBP-TR-IND-2018-2020 (Call for TRANSFORMING EUROPEAN INDUSTRY)

Number of Participants: 10
Role: Partner
Project number: H2020-NMBP-TR-IND-2018-2020-953138-2

Objective: Cardiovascular diseases (CVDs) account for 45% of deaths in Europe and are estimated to cost the EU economy €210 billion a year. However, only four drugs targeting cardiovascular diseases have been approved for use in the last decade. Thus, models that could effectively simulate diseased tissues, would enable the accurate assessment of the efficacy of the pharmaceuticals, and would accelerate drug development are urgently needed. The main bottleneck towards such models is the foetal-like state of the human induced pluripotent stem cell (hiPSC) derived cardiomyocytes (CMs). That is hiPSC-CMs do not reach adult-like maturity. The objective of this project is to produce a platform for growth and maturation of cardiac microtissues for adult-like organotypic models in healthy and diseased states. To achieve that, biomimetic microenvironment that provides all the needed stimuli (electrical, mechanical, topological (3D environment) and biochemical (release of active molecules)), during the maturation of hiPSC-CMs will be developed. This will be achieved by combining electromechanoactive polymer-based scaffolds (EMAPS) with bioactive membranes. To characterize the effects of CVD drugs, the contractility of the microtissue will be monitored continuously and simultaneously (over 24-wells) using the sensors developed during the project. To increase the sensitivity and accuracy of the model, deep-learning based algorithms to detect the effects of drugs in vitro will be developed and verified. The goals will be achieved by a multidisciplinary consortium with complementary know-how of three academic units and seven small companies. The increased sensitivity and accuracy of organ-on-chip devices is a needed leap in technology that will accelerate new drug development without the need for animal models; the project aims to provide a platform for the realization of such physiologically-relevant organotypic models.

European consortium for communicating gene- and cell-based therapy information

H2020-SC1-BHC-2018-2020 (Call for Better Health and care, economic growth and sustainable health systems)

Number of Participants: 49
Role: Partner
Project number: H2020-SC1-BHC-2018-2020- 965241
Project website: www.eurogct.org

Objective: The European Consortium for Communicating Gene and Cell Therapy Information (EuroGCT) unites 49 partner organisations and institutions across Europe, including the major European advanced therapies learned societies, with the common goal of providing reliable and accessible information related to cell and gene therapy development to European stakeholders. EuroGCT has two major objectives:

• To provide patients, people affected by conditions, healthcare professionals and citizens with accurate scientific, legal, ethical and societal information and with engagement opportunities, and thus to support better informed decisionmaking related to cell and gene-based therapies.
• To facilitate better decision-making at key points in development of new therapies and thus enable improved product development, by providing the research community and regulatory and healthcare authorities with an information source on the practical steps needed for cell and gene therapy development.

To achieve our aims, EuroGCT will adopt a highly structured system for coordinated management of information related to cell and gene therapy development and, from this, will implement an ambitious programme of online and direct stakeholder information provision and engagement. All outputs will be delivered in 7 European languages, to ensure broad accessibility, and will be rigorously evaluated against measurable objectives throughout the project duration. The proposed consortium comprises leading cell and gene therapy-related organisations and basic and clinical research labs across Europe, including new member states; together with experts in product development, ethical, legal and societal issues, and in evaluating clinical outcomes; patient representatives; and science communicators. It thus is uniquely placed to develop a world-leading cell and gene therapy information resource and to meet the challenge outlined in Topic SC1-HCO-19-2020.

Directing the immune response through designed nanomaterials

H2020-MSCA-ITN-2020
Number of participants: 12 + 5
Role: Associated partner
Project number: H2020-MSCA-ITN-2020-956544

Objective: DIRNANO provides a highly integrated and interdisciplinary training of next-generation Early Stage Researchers (ESRs) at the interface of nanopharmaceutical bioengineering and its translation on preclinical and human immunology.

DIRNANO will develop biocompatible nanopharmaceuticals with either “super”-stealth or immune-specific behavior for cancer immunotherapy and vaccination by mapping nanoparticle-immune interactions through two core approaches: 1) inception of novel surface engineering approaches, based on new organic polymers, zwitterionic lipids and conjugation chemistry strategies, 2) engineering of host or microbial-derived modulators of innate immunity (e.g. complement system).

DIRNANO team comprises internationally renowned scientists and industrialists at the forefront of nanoengineering, pharmaceutical sciences, molecular biosciences, commerce and business, thereby generating a unique pan-European macro-environment for interdisciplinary training of ESRs at the highest international level. Through participation of industrial partners, we will furnish ESRs with in-demand industrial and business skills, including process manufacturing, reproducibility and regulatory challenges, intellectual property and commercialization strategies.

DIRNANO will lead to rational engineering of broader libraries of NPs with tunable immune-modulating functions. The combinatorial analysis of new nanomaterial core-coat scaffolds will improve temporal and spatial understanding of biomaterial-innate immune interactions at the molecular level, thereby filling the void in overcoming adverse reactions to nanopharmaceuticals injection. DIRNANO will drive future development of small molecules and biologics-based nanopharmaceuticals through a “low-risk-high gain” perspective and within the context of personalized therapies and precision medicine. As such, DIRNANO, will extensively contribute to European science, education and socioeconomics value, skill retention and brain-gain.

Closed H2020 and other international projects

Integration of Nano- and Biotechnology for Beta-cell and Islet Transplantation

H2020-NMBP-2016-2017 (Call for Nanotechnologies, Advanced Materials, Biotechnology and Production)
Number of participants: 8
Role: Coordinator
Project number: H2020-NMBP-15-2017-760986

Objective: The iNanoBIT project is aimed to apply nanotechnologies for imaging porcine pancreatic islet cellular transplants and induced pluripotent stem cell-derived beta-cells and subsequent regenerative processes in vivo in a porcine model. The project will develop1) novel highly sensitive nanotechnology-based imaging approaches allowing for monitoring of survival, engraftment, proliferation, function and whole body distribution of the cellular transplants in a preclinical porcine model with excellent translational potential to humans; 2) develop and validate the application of state-of-the-art imaging technologies facilitating the provision of new regenerative therapies to preclinical large animal models and patients; 3) directly contribute to the opening of a new market sector for i) imaging equipment (SPECT, PET/MR, optoacoustic imaging in preclinical large animal models and patients), ii) nano-imaging molecule supplies (nanomolecules allowing multimodality imaging of specific cell types with high sensitivity), iii) validated transplantable in vitro differentiated human beta-cells and porcinexenotransplant islets thus will reinforce the European healthcare supply chain for regenerative medicinal products. The iNanoBIT project will provide the currently missing toolbox for preclinical/clinical testing for a safe translation of regenerative medicinal cellular and tissue products, currently under preclinical and clinical trials, which is vital for the competitiveness of the European healthcare sector in this fast-growing area. The consortium of 5 SME and 3 Academic partners is coordinated and driven by the industrial partners from the field of nanotechnology, imaging and stem cell technologies, providing a perfect match and unique combination addressing the scope and expected impact of the call and providing TRL 3/4 starting points for the key technological elements, and expect to arrive to TRL6 levels of validated technologies ready for marketing by the end of the project.

Periconceptional Programming of Health Training Network

H2020-MSCA-ITN-2018 — Marie Skłodowska-Curie Innovative Training Networks
Type of action: MSCA-ITN-ETN (European Training Networks)
Number of participants: 20
Role: Coordinator
Project number: Project No. 812660
Project website: http://dohartnet.eu/

Altered conditions during the periconceptional (PC) period of gamete maturation and early embryonic development have long lasting effects on the health of the progeny, including the childhood, adolescent and adult-life onset of cardiovascular, metabolic and neurological diseases (‘Developmental Origins of Health and Disease (DOHaD) concept).
Increasing evidence from epidemiological and animal model studies shows that children worldwide exhibit conditions and disease risks associated with the exposures of their parents, including chemical stressors before and during pregnancy, reproductive failure, adverse pregnancy outcome, diabetes, obesity and nutritional compromise.
Babies born following human ART (“testtube”) interventions render this population (over 6 million world-wide) one of the largest well-defined clinical cohorts to be studied for a better understanding of the future risk of disease for current and succeeding generations in Europe.

The DohART-NET project focus on the integration of pre-clinical (animal and stem cell-models) and clinical studies and apply data linkage, bioinformatics and network science for the identification and validation of mechanisms of diseases common in early development. The project will exploit our new understanding to promote efficient disease prevention and potential personalised therapeutic interventions in both the general and ART populations to overcome adverse disease pathways.
DohART-NET is optimized for training ESRs due to the facts that: 1.) the topic is progressive, and much needed to improve public health over several generations, and it is integrating basic pre-clinical, translational clinical and in silico modeling approaches. 2.) the partnership has a highly multi- and interdisciplinary scientific and training expertise and excellence 3.) there is an existing synergy by collaborations and links that the partners wish to strengthen both in science and lasting training programs in a highly inter-sectorial setting.
Specific ESR individual projects will make a major contribution to the goals of the project and along with secondments are fully integrated into the overall research programme.

Transport derived Ultrafines and the Brain Effects

EU H2020 Research and innovation actions (RIA)
Participant’s number: 14
Role: Partner
Project number: H2020-MG-2018-2019-2020
Project website: https://www.tube-project.eu/

Objective: The aim of the research is to study the effects of smallest traffic related ultrafine- or nanoparticles beyond the lung on brain health. Air pollutants have been shown to cause a vast amount of different adverse health effects. These effects include impairment of many respiratory (e.g. asthma, COPD) and cardiovascular (ischemic heart disease, infarction, stroke) diseases. However, in recent years, the evidence showing effects beyond the lungs and circulatory system are becoming more evident. Neurological diseases, namely Alzheimer´s disease (AD) has shown to be associated with living near traffic. However, reason for this has remained unresolved until today. This consortium aims on revealing the mechanisms and exposures both behind cardiorespiratory diseases and beyond the current knowledge in neurological diseases. This consortium includes experts in areas of aerosol technology, emission research, engine and fuel research, human clinical studies, epidemiology, emission inventories, inhalation toxicology, neurotoxicology and disease mechanism studies. This enables research of resolving the effects of nanoparticles from different traffic modes for both air quality and concomitant toxic effect of these air pollutants. In this study, we will investigate adverse effects of air pollutants using cell cultures, animal exposures and volunteered human exposures as well as the material from epidemiological cohort study. These are going to be compared according to inflammatory, cytotoxic and genotoxic changes and furthermore beyond the current state of the art to neurotoxic and brain health effects. With this approach, we are aiming in to a comprehensive understanding of the adverse effects of nanoparticles from traffic. In current situation only particles above 23nm are measured in regulations, traditional toxicological methods are used in risk assessment and emission inventories and regulations are largely based on old technology engines. Our project will change this.

From air pollution to brain pollution – novel biomarkers to unravel the link of air pollution and Alzheimer’s disease

JPND call for proposals: “Multinational research projects on Personalised Medicine for Neurodegerative Diseases”

Number of participants: 8
Role: Partner
Project number: 250619
Project website:  https://adair-jpnd.eu/

Objective: Despite decades of Alzheimer’s disease (AD) research, the real molecular pathophysiology of the disease is still poorly understood, and treatments remain inadequate. Remarkably little attention is paid to the involvement of environmental factors, which are known from epidemiological studies to strongly impact AD development. Air pollution, a massive public health issue known to pose a major threat to humans, is an increasing global concern. A growing body of evidence from epidemiological and controlled animal studies shows that exposure to air pollutants also impairs the brain. Furthermore, living in highly polluted areas is associated exacerbated cognitive dysfunction and AD. However, many questions remain unanswered as mechanistic information on air pollutant effects is scarce. Importantly, biomarkers for air pollution and AD risk prediction do not currently exist, thus hindering the identification and stratification of individuals at risk for harmful air pollution effects.
Drawing upon a unique combination of expertise and state-of-the-art methods and tools in neurobiology, epidemiology, clinical science, environmental science and data science, the ADAIR consortium is uniquely placed to, for the first time, provide crucial mechanistic insight about the effects of air pollutants on the brain in humans and discover biomarkers for air pollution and AD risk prediction. ADAIR applies a precision medicine approach to stratify individuals to subgroups for risk estimation and future AD prevention, ultimately aiming to target air pollution induced effects in those individuals that can most benefit from them. The project investigates the novel, ambitious hypothesis that the pollutant exposure environment of an individual alters cellular mechanisms and functions, resulting in the expression of measurable biomarkers. By identifying biomarkers, the individuals with increased AD risk can be stratified prior to the disease onset and preventive measures can be targeted to the specific at-risk populations in order to be most effective.

ADAIR address a major societal challenge with wide health-related, environmental, economic, scientific, social, and political impact. Lowering the burden of AD attributable to air pollution and contribution to the mitigation of climate change, are closely linked. The ultimate goal is to develop strategies for early identification of people at risk of AD, and to discover novel targets for preventive strategies to reduce the health care and socio-economic burden of AD.

An integrated interdisciplinary approach to animal-free nanomaterial and chemical safety assessment.

Marie Curie – Innovative Training Network (ITN)
Participant’s number: 13
Role: Participant
Project number: H2020-MSCA-ITN-2016 – 721975
Project website: estiv.org/in3/

Objective: The in3 project is a Marie Curie Innovative Training Network that aims to drive the synergistic development and utilisation of in vitro and in silico tools for human chemical and nanomaterial (NM) safety assessment. The project will focus on differentiation of human induced Pluripotent Stem Cells (hiPSC) to toxicologically relevant target tissues including; brain, lung, liver and kidney. The tissues, from the same genetic backgrounds, will be exposed to several compounds and the data generated will be used to develop safety assessment approaches by integrating cheminformatics, mechanistic toxicology and biokinetics into computational models. The project will hire 15 PhD students to carry out these activities in a coordinated and highly collaborative fashion. The scientists trained within in3 will acquire a unique multidisciplinary skill set giving them a competitive employment advantage in safety assessment sciences either in industry, governmental bodies or academia.

Core scientific activities:

•  Differentiation of well-characterised human iPSC into brain, lung, liver, kidney and vascular cells
•  Delineation of tissue specific and donor specific effects of compound exposures (uptake, metabolism, extrusion, and mechanistic toxicity)
•  Development and optimisation of quantitative adverse outcome pathways (qAOPs) for each target organ which will be unified in an organism-level model
•  Optimisation of QSAR and read-across tools for safety assessment
•  Ultimately to create a unified expandable integrated testing strategy for chemical and NM safety assessment

Interdisciplinary training network on the purinergic P2X7 receptor to control neuroinflammation and hyperexcitability in brain diseases

H2020-MSCA-ITN-2017
Marie Skłodowska-Curie Actions Innovative Training Networks (ITN)
Number of participants: 9
Role: Participant
Project number: H2020-MSCA-ITN-2017- 766124
Project website: https://cordis.europa.eu/project/id/766124

Objective: Brain disorders affect ~179 million people and their families in Europe alone, with an annual cost to the taxpayer estimated at €800 billion- a greater economic burden than cardiovascular disease and cancer combined. Despite diverse etiology, overlap in clinical symptoms and comorbidities between brain disorders suggests shared patho-mechanisms. In particular, hyperexcitible states driven by glial activation and neuroinflammation appear near ubiquitous. Targeting these mechanisms offers the potential to ameliorate symptoms and reverse disease progression across a broad span of brain disorders. Functioning as a gatekeeper to neuroinflammation and mechanistic link between neuronal hyperexcitability and glial activation, the ATP-gated, ionotropic purinergic P2X7 receptor (P2X7R) offers the most promising target for pharmacological intervention in the neuroinflammation-hyperexcitability pathway, to date. With breakthroughs in understanding P2X7R function, highly promising effects demonstrated for antagonists in models of brain disease and vast investment in P2X7Rrelated drug development programmes, now is the perfect time to pool resources. PurinesDX brings together global leaders in translational research in purinergic signalling, Europe’s leading clinical specialists in a broad range of brain diseases, and industrial partners specializing in drug and biomarker development.

Calcium-Sensing Receptor (CaSR): Therapeutics for Non-Communicable Diseases

EU H2020 Marie Sklodowska-Curie Innovative Training Networks (ITN)
Participant’s number: 13
Role: Participant
Project number: H2020-MSCA-ITN-2015 – 675228
Project website:casr.meduniwien.ac.at/

Objective: The calcium sensing receptor (CaSR) is a class C Gprotein-coupled receptor that plays a pivotal role in systemic calcium metabolism by regulating parathyroid hormone secretion and urinary Ca excretion. Abnormal CaSR function is implicated in calciotropic disorders, and in non-calciotropic disorders such as Alzheimer’s disease (AD), cardiovascular disease (CVD), diabetes (DM), sarcopenia and cancer, which account for >25% of the global disease burden. The CaSR is a unique GPCR whose principal physiological ligand is the Ca2+ ion; it is expressed almost ubiquitously; interacts with multiple Gα subtypes regulating highly divergent downstream signalling pathways, depending on the cellular context. The CaSR Biomedicine is a fully translational project that utilises the concept of a single molecule, the CaSR, influencing a range of physiological and disease processes, to develop a unique, strong multidisciplinary and intersectoral scientific training programme preparing 14 young scientists to become specialists in GPCR biology and signalling.The objectives of CaSR Biomedicine are:1. Educate and train Early Stage Researchers to become highly innovative scientists to enhance their career perspective. 2. Elucidate ligand- and tissuedependent differences in CaSR physiology by examining its functions at cellular level and thus to contribute to the understanding of GPCR signalling in general; 3. Assess how CaSR function is altered in AD, CVD, DM, sarcopenia, and cancer, and to find innovative CaSR-based therapeutic approaches for these major, age-related disorders.4. Establish long-lasting interdisciplinary and intersectoral cooperation among researchers and between researchers and industry, to strengthen the European Research Area.Therefore the CaSR Biomedicine will investigate the complexity of CaSR signalling and function to identify CaSR-based therapeutic approaches to diseases linked to changes in CaSR expression or function (AD, CVD, DM, sarcopenia, and cancer).

Next Generation Science Challenges Using Digital and Social Media to Make Science Education and Careers Attractive for Young People

EU H2020 Industrial Leadership and Societal Challenges Department, Spreading Excellence, Widening Participation, Science with and for Society (SEAC)
Participant’s number: 9
Role: Partner
Project number: H2020-SEAC-2014-2015 – 665868
Project website: www.scichallenge.eu

Objective: Science education is tremendous in shaping the present and future of modern societies. Thus, the EU needs all its talents to increase creativity and competitiveness. Especially young boys and girls have to be engaged to pursue careers in Science, Technology, Engineering and Mathematics (STEM). However, statistics still show that enrolment rates in STEM-based degree programs are low and will lead to a workforce problem in industries, especially in many of the new member countries. The SciChallenge project focuses on developing novel concepts to actively integrate young boys and girls in science education using a contest-based approach to self-produced digital education materials from young people for young people. Driven by inspirational topic sheets, guides and toolkits created through this project and distributed by partner schools, teachers, and other youth-oriented institutions, contestants (individuals or groups) between the ages of 10 to 20 will generate creative digital materials (videos, slides, or infographics). The initiative will broadcast and distribute content over various social media channels and aggregated on a modern SciChallenge Web Platform (www.scichallenge.eu) to generate wide reaching awareness and promotion. Winning submissions will receive prizes funded by science-oriented industry and stakeholders. Intelligent cross-sectoral positioning of various awareness modules on the SciChallenge Open Information Hub will increase awareness on science careers and open opportunities for youngsters on internships or taster days in STEM through the strong involvement of related organisations and industries. Additionally aggregated information on science events (slams, nights, festivals etc.) is shared. With this multi-level approach, SciChallenge will boost the attractiveness of science education and careers among young girls and boys leading to more public engagement in science, economic prosperity and global competitiveness on a pan-European level.

Design and development of advanced NAnomedicines to overcome Biological Barriers and to treat severe diseases

EU H2020 Marie Skłodowska-Curie Innovative Training Networks (ITN-ETN)
Participant’s number: 6
Role: Associated Partner
Project number: H2020-MSCA-ITN-2014- 642028
Project website: www.nabbaproject.eu

Objective: Many therapeutic targets are shielded behind biological barriers, limiting the possibility to reach them with conventional drugs or diagnostic probes. Biological barriers are even more problematic for most biological pharmaceutics, such as recombinant proteins, antibodies and gene therapeutics. The most promising solution to this challenge is the use of nano-vehicles for specific targeting and delivery. The aim of NABBA is to form European early stage researchers (ESR) with cutting-edge scientific knowledge in the field of nanoparticles (NP) for biomedical application, able to cross biological barriers. For this aim the project will train ESRs, focusing on key aspects of nanobiotechnology: (i) design and chemical synthesis of different types of NPs, (ii) related techniques of detection and characterization, (iii) strategies of loading, targeting and delivery of drugs or diagnostic probes; (iv) proof of principle of pharmacological activity including pharmacokinetics and biodistribution. As a peculiar feature of NABBA, strong emphasis will be devoted to molecular mechanisms ruling biological barriers under physiological and pathological conditions, in order to develop novel nano-technological expedients for their crossing. Strong emphasis will be devoted to advanced chemistry issues, enabling new synthetic strategies either for NP assembly or functionalization. Different biological barriers will be addressed. ESRs will strongly benefit from a network of internationally recognized scientists in the field of chemistry, nanobiotechnology and nanomedicine, and the participation of companies with relevant interests and expertises in the field. The planned cooperation programs between Academia and Industries will allow the circulation of ESRs and this will give them the opportunity for to get acquainted with the most advanced research in the field, the most sophisticated technologies and the most advanced Industrial manufacturing platforms and innovative strategies.

V4RM – Bridging the gap between science, education and enterprise in regenerative medicine

Number of Participants: 5
Role: Partner
Project number: 22020272

Project website: https://v4rm.net/en/

Objective: The mission of the V4RM network is to provide an interface between science, education and business communities involved in the field of Regenerative Medicine in Visegrad countries and Ukraine.

The network is intended to become a basis for the establishment of wide consortia of organizations for generating future collaborative grant applications, promotion of student exchanges and growth of competitiveness of organizations within the world.

We believe gaining the best practices from the neighbouring countries would bridge the gap in the communication and bring significant long-lasting impact in the development of the regenerative medicine in the region. We expect to increase the success rate of our collaborative research projects, young scientist exchanges, as well as improve the overall business/research/education cooperation.

The project is co-financed by the Governments of Czechia, Hungary, Poland and Slovakia through Visegrand Grants from International Visegrad Fund. The mission of the fund is to advance ideas for sustainable regional cooperation in Central Europe.

Setting an interdisciplinary/sectorial/international research network to explore dry storage as an alternative strategy for cells/germplasm biobanking

H2020-MSCA-RISE-2016
(Marie Skłodowska-Curie Research and Innovation Staff Exchange)
Number of participants: 8
Role: Participant
Project number: H2020-MSCA-RISE-2016-734434
Project website: https://sites.google.com/unite.it/drynet/

Objective: The number of biobanks for diagnostic/clinical/biodiversity preservation purposes is increasing exponentially, representing an economic burden for the EU. Cryopreservation (Liquid Nitrogen LN) is the only cells/gametes long-term repository method. LN storage is expensive though, requires dedicated facilities, is hazardous, carries pathogens and has high carbon footprint. DRYNET objective is to set an inter-sectorial/multidisciplinary/international network between EU academic (5), SME (3), the EU pan-Biobank, and international partners (Japan/Thailand), with the aim of sharing knowhow & expertise to lay down the theoretical and early empirical basis for the dry storage of cells/germplasm. DRYNET merges the partner’s expertise, theoretical/ biophysical/ mathematical modelling, cellular/ molecular/ insect biology, embryology, mechanical engineering into a coherent approach towards dry storage of cells/germplasm. International/inter-sectorial secondments, with meeting/workshop/summer school will be primary tools to implement our strategy for biobanking. Outreaching activities will guarantee public awareness of the project. DRYNET’s relies on water subtraction to induce a reversible block of metabolism, a survival strategy available in nature (anhydrobiosis). The work plan foresees the exploitation of natural xero-protectants (Late Embryogenesis Abundant proteins), loaded/expressed in gametes/cells, before drying. The best drying approaches, supported by theoretical/biophysical/math modelling, will be implemented by SMEs/academy partners. DRYNET will bring a simplification of currents practices, with cost and carbon footprint reduction, for the maintenance/shipping of biobanks. DRYNET will generate young scientists with transferable skills, ensuring career prospect in academia/industry. DRYNET strengthens the international/sectorial network between different disciplines, ensures long-term sustainability of the project, and boosts European competitiveness in biobanking.

An Integrated EUropean ‘Flagship’ Program Driving Mechanism-based Toxicity Testing and Risk Assessment for the 21st Century

EU H2020 Research and innovation actions (RIA)
Participant’s number: 25
Role: Partner
Project number: H2020-PHC-2015-single-stage_RTD- 681002
Project website: https://www.eu-toxrisk.eu/

Objective: The vision of EU-ToxRisk is to drive a paradigm shift in toxicology towards an animal-free, mechanism-based integrated approach to chemical safety assessment. The project will unite all relevant disciplines and stakeholders to establish: i) pragmatic, solid read-across procedures incorporating mechanistic and toxicokinetic knowledge; and ii) ab initio hazard and risk assessment strategies of chemicals with little background information. The project will focus on repeated dose systemic toxicity (liver, kidney, lung and nervous system) as well as developmental/reproduction toxicity. Different human tiered test systems are integrated to balance speed, cost and biological complexity. EU-ToxRisk extensively integrates the adverse outcome pathway (AOP)-based toxicity testing concept. Therefore, advanced technologies, including high throughput transcriptomics, RNA interference, and high throughput microscopy, will provide quantitative and mechanistic underpinning of AOPs and key events (KE). The project combines in silico tools and in vitro assays by computational modelling approaches to provide quantitative data on the activation of KE of AOP. This information, together with detailed toxicokinetics data, and in vitro-in vivo extrapolation algorithms forms the basis for improved hazard and risk assessment. The EU-ToxRisk work plan is structured along a broad spectrum of case studies, driven by the cosmetics, (agro)-chemical, pharma industry together with regulators. The approach involves iterative training, testing, optimization and validation phases to establish fit-for-purpose integrated approaches to testing and assessment with key EU-ToxRisk methodologies. The test systems will be combined to a flexible service package for exploitation and continued impact across industry sectors and regulatory application. The proof-of-concept for the new mechanism-based testing strategy will make EU-ToxRisk the flagship in Europe for animal-free chemical safety assessment.

Stem Cell Center of Excellence in Neurology

Program: Innovation Fund Denmark

Number of Participants: 12 partners and 3 external collaborators
Role: External collaborator
Project number: 4108-00008B

Project website:  https://brainstem.dk/

Objective: Objective/abstract: The key objective of BrainStem is to improve therapy and diagnostics of AD, FTD, and PD by development and application of patient-specific iPSC-derived in vitro and in vivo models. Scientifically, the objective is to use these models to investigate molecular and cellular disease mechanisms in patient-specific neurons and glial cells by applying front-line methodologies in transcriptomics and proteomics. This includes the development of improved protocols for in vitro neural differentiation, derivation of gene-edited control and disease cell lines, as well as aggravation of molecular pathology by genetic modification. Industrially, the objective is to use the established in vitro and in vivo models and the generated knowledge for identifying new targets and validating existing drug targets. Societally, the objective is to use the iPSC in vitro cell models for development of cell-based tools for earlier and stratified AD diagnosis, and thus enhanced treatment outcome, life quality, and reduced health care budgets. Ethically, we will analyse and propose strategies for how to deal with issues with broad societal significance, focusing on concerns over privacy and autonomy when obtaining consent for biobanking. Thus, BrainStem will directly use patient-specific stem cell tools for improved and sustainable treatment and diagnostics providing exciting industrial opportunities.

Closed FP6 and FP7 projects