X-TREME 6G proposal relies on a unique industry led consortium to provide a foundational open microelectronics platform in Europe with the objective to create and design key disruptive next generation chiplets and chipsets for 6G use cases. The idea is to break-up the full potential of best-in-class Silicon BiCMOS, InP and heterogeneous 3D integration for high capacity radio access technologies such as wireless back-hauling at sub-TeraHertz frequencies, Joint Communication And Sensing, Non Terrestrial Networks and Network as a Sensor. New classes of chipsets will unleash the full potential of 6G and enable the emergence of new applications through specific developments for the underpinning novel microelectronic technologies. X-TREME 6G valorizes also resource efficient 6G algorithms and an ML/AI software toolbox for computationally efficient silicon-ready baseband extensions. Part of the SNS “Microelectronic Lighthouse” visionary initiative, the proposal’s ambition is to establish and maintain a sustainable open platform for the duration of the SNS program and beyond, to support 6G verticals. By nurturing the links with the emerging Chips JU pilot lines, the platform acts as a first fabric to accelerate joint initiatives between SNS and Chips JUs. In a nutshell, X-TREME 6G will provide tangible contributions towards an experimentation EU framework for 6G, demonstrating the full benefit of the newly developed chipsets and chiplets for a set of emerging 6G high potential use cases (wireless back-hauling, JCAS, NTN, NaS); while being open to dynamically support the emerging 6G ecosystem (SMEs, Industries, Service Providers, Government etc.) and evaluate additional 6G challenges and expectations. By strengthening and extending the 6G functionality and microelectronics supply chain, X-TREME 6G contributes towards a network-centric democratized and open 6G ecosystem able to release the current hyperscaler’s market embrace, while empowers European Industry at large.

The trans-Golgi network (TGN) serves as a central sorting station of membrane traffic standing at the intersection of secretory and endocytic pathways, a feature that is now proposed to be a common trait between plant, yeast and animal cells. The multi-identity of TGN relies on its partitioning in subdomains but, due to the lack of resolution in conventional microscopy, it is still poorly understood how TGN subdomains relate dynamically to each other, or acquire their identity, and how they achieve the sorting of a variety of cargo proteins to different destinations. The applicant previously identified of at least two subdomains, one labeled by the R-SNARE VAMP721 and the coat protein AP-1 and that is involved in secretory trafficking, and another labeled by VAMP727 and AP-4 and that is involved in vacuolar trafficking. The host lab previously demonstrated by lipidomic analyses that sphingolipids with very long chain fatty acid were enriched in Q-SNARE SYP61-labelled TGN compartments and were critical for polar sorting of the auxin carrier PIN2 to apical plasma membrane. The goal of this project is now to join forces, expertise and scientific networks to gain from each other and tackle the challenging questions of: 1) what is the exact structure of TGN, how are TGN subdomains spatially arranged between each other and how do they behave dynamically, this will be addressed by super-resolution microscopy, 2) what is the proteo-lipidic composition of TGN subdomains and what is the role of lipids in TGN partitioning, 3) how the identified subdomains are functionally important for cargo sorting and trafficking to different destination by employing a novel pulse-chase method. This project is timely, realistic, focused and represents a unique combination of expertise from the applicant in super-resolution 3D live imaging of TGN subdomains and the host lab in TGN-mediated trafficking, lipid analytical biochemistry and super-resolution imaging.

ABCardionostics envisions an innovative multi-marker-based positron emission tomography (PET)/ magnetic resonance imaging (MRI) system for efficient staging and personalized treatment of vulnerable patients with atherosclerosis. To provide a snapshot of plaque composition, along the arterial tree of at-risk patients, human antibodies (HuAbs) targeting different affected arterial sites will be developed. Importantly, HuAbs targeting culprit and protective monocyte/macrophage (MoMP) populations that are instrumental in plaque progression will be crucial to assess disease status and reprogramme an unbalanced functional state toward atheroprotection. To translate this concept into clinical practice, the ABCardionostics consortium will combine cutting-edge biotechnologies and in silico and computing analyses to close the knowledge gaps on plaque MoMP spatiotemporal dynamics and the lack of imaging approaches for multi-marker detection: pioneering in vivo and in vitro phage display approaches to identify relevant HuAbs (UBx), multispectral mapping and MacroScreen to unravel the functionomics of MoMP subsets in atherosclerosis (MUNC), unvisited in silico and biochip development to identify HuAb targets (MAbS, CNRS-TBI), innovative HuAb bioengineering techniques (CNRS-BacFly, and UBx-INP, BTM), derivatization and labelling to develop PET tracers to finally explore the feasibility of a translational non-invasive multi-marker PET/MRI system for diagnosis and monitoring (CNIC) and an adapted immunotherapy strategy targeted to the appropriate plaque by designing bispecific antibodies (CNRS-BacFly). Data processing will integrate multimodal images to obtain insight into plaque morphology and composition (PMI). ABCardionostics successful completion will bring HuAb leads for atherosclerosis theranosis, and novel tools for HuAb identification and design, easily transposable to other diseases, revolutionizing the current imaging and therapeutic approaches.

The integrase inhibitors dolutegravir (DTG) is recommended by the World Health Organization (WHO) for 1st line antiretroviral therapy (ART) in people living with HIV (PLHIV) since 2018. Despite its high virologic efficacy, there is growing evidence showing massive weight gain and high incidence of metabolic disorders (obesity, type 2 diabetes) and hypertension under DTG, notably among women from sub-Saharan Africa (SSA) women, along with mental health and quality of life issues. The non-nucleoside reverse transcriptase inhibitor doravirine (DOR) is a potent novel ART, recommended in European and North-American guidelines, but not used so far in Southern countries despite interesting virological, safety and resistance profiles. In this context, the ELDORADO project will generate high-quality data on DTG-based ART toxicity and evaluate DOR as an alternative for 1st-line HIV-1 treatment in order to support national and international policymakers in updating national and international guidelines and practices aimed to improve patient outcomes and reduce disease burden of HIV in sub-Saharan Africa and worldwide. The project includes i) a randomized clinical trial assessing the non-inferiority of DOR-based ART as compared to DTG-based ART in terms of virologic efficacy, and its superiority in terms of key safety endpoints (obesity, diabetes, hypertension) in 610 PLHIV from diverse ethnic backgrounds across in SSA (Cameroon, Côte d’Ivoire, Mozambique), Brazil, Thailand, and France, ii) innovative assessments of organ lesions, iii) assessments of mental health and quality of life, iv) health impact and economics modelling based on the trial results as well as that of other trials (NAMSAL) and cohorts (IeDEA West Africa and Brazil). The project will also prioritize capacity building for junior investigators and community advisory board. The ELDORADO trial will be confounded in non-SSA countries by the ANRS|MIE (trial sponsor) and MSD, and benefits from support from the WHO.

Human populations are impregnated by various types of chemical pollutants reported as “hazardous waste” present in the environment. Certain pollutants have adverse effects on brain, but the underlying mechanisms and time-window exposures are still unknown, as well as their contribution on dementia, the 7th leading cause of death. EXPOSIGNALZ project aims to delineate the impact of a selection of environmental pollutants on brain health throughout life and their role in dementia especially Alzheimer’s disease (AD) representing about 70% of dementia cases. Through interdisciplinary approaches, integrating experimental and epidemiological studies, our objectives are to: 1) Identify environmental pollutants likely to have neurotoxic effects and pro-amyloidogenic properties predictive of a neurodegenerative trajectory related to AD using in vitro screening models; 2) Characterize pollutant signatures associated with brain aging and AD in biological matrices of 4 European population-based cohorts of various age groups; 3) Understand the mechanisms of action of pollutants identified in the in vitro screenings and those found in biological signatures, using AD-iPSC and AD preclinical models; 4) Explore the impact of pollutants on early neurodevelopment as a factor of susceptibility for later neurodegenerative diseases using brain organoids and gestational contamination models and 5) Disseminate knowledge to policy makers, to the relevant stakeholders and general public in order to define guidelines for disease prevention and take actions for population’s health. The project, which aims to identify chemical pollutants as new risk factors for dementia as well as new pollutant-associated biomarkers, could contribute to: (i) reduce or delay the incidence of AD, and thus reduce the economic and social burden; and (ii) allow an earlier diagnosis of AD combined with new disease modifying treatments to delay the entrance of patients in the more severe stages of the pathology.