The COVID pandemic can be seen as an experiment done with the entirety of humankind (as almost everybody has been or will get infected with SARS-CoV-2). It will therefore have the best coverage over the widest variation possible and is therefore ideally suited to study the effects of infections with SARS-CoV-2 on large quantities of heterogeneous individuals. In our project, we will focus on neurodegenerative diseases (NDDs), namely Alzheimer and Parkinsonism, as the NCDs under investigation. COMMUTE is a project characterized by the intelligent combination of two fundamentally different approaches: a hypotheses-free, data-driven approach is building on available big data and the application of cutting edge AI/ML technologies to answer the question, whether infection by SARS-CoV-2 causes effects that result in a higher risk for the development of NDDs at population-level. Complementary to that, a hypothesis-driven, knowledge-based approach leverages the substantial knowledge in the scientific community working on NDDs on the putative comorbidity mechanisms linking COVID and neurodegeneration. Both approaches are informing and supporting each other through an intensive crosstalk between computational and experimental biology methods. Understanding comorbidity between COVID and NDDs at causal level is the first goal of the COMMUTE project. The second goal is the translation of the actionable insights into personalized health applications. On the AI/ML side, the targeted outcome for translation into practice is a set of qualified biomarkers and predictive features that will be used for an AI-powered, model-generated recommender system that will allow for individualized risk assessment and personalized recommendations. On the side of the biomedical assay systems, COMMUTE will use cell-based assays based on clear pathophysiology mechanism understanding for drug-repurposing screenings in collaboration with REMEDI4ALL, the largest of the EU drug repurposing platforms.

Over 30% of EU citizens at vulnerable stages and situations in life are at increased risk to transgress from healthy weight to overweight and further to obesity. Though many interventions to tackle obesity have been proposed, they have rarely been effective. The aim of HealthyW8 is to advance the efficacy of current and future efforts and investments in obesity prevention initiatives across Europe. Most interventions suffer from not adapting to personal context (e.g. socioeconomic aspects, host-biological factors, environment, dietary preferences, fitness level etc.), focus only on diet or physical activity alone, do especially overlook emotional aspects, and fail to engage and motivate the user. Thus, initiatives on obesity prevention in policy and practice are often of marginal impact. HealthyW8 will address these shortcomings by iteratively developing, together with stakeholders, a digital-based healthy lifestyle recommender for evidence-based, tailored interventions and tools including a human digital twin to bridge the gap between science, societal actors and stakeholders (e.g. healthcare professionals, food industries, policymakers) and EU citizens. The targeted populations are those undergoing transitions, i.e. schoolchildren (5-10 y, and their parents), young adults (18-25 y) and the elderly (>65 y). In the mid-term, we estimate that with 200,000 HealthyW8 users, we will prevent 10,000 obesity cases/y. In the long run, the impact will be maximized through adopting the project’s proposed methodology, platform and tools by as many EU institutions and entities as possible. HealthyW8 is a highly experienced, synergistic and complementary consortium that will built on a previously developed digital dietary app (LIFANA) and draw on transdisciplinary research in pan-EU multicentre pilots and long-term randomized control trials to achieve its overarching objective of increasing impact of current and future obesity prevention interventions and policies in the EU.

Antimicrobial resistance (AMR) is of great public health concern, causing numerous losses of lives worldwide and threatening to reverse many of the considerable strides modern medicine has made over the last century. There is a need to stratify antibiotic and alternative treatments in terms of the actual benefit for the patient, improving patient outcome and limit the impact on AMR. High quality, effective and appropriate diagnostic tests to steer appropriate use of antibiotics are available. However, implementation of these tests into daily healthcare practice is hampered due to lack of insight in the medical, technological and health economical value and limited knowledge about psychosocial, ethical, regulatory and organisational barriers to their implementation into clinical practice. VALUE-Dx will define and understand these value indicators and barriers to adoption of diagnostics of Community-Acquired Acute Respiratory Tract Infections (CA-ARTI) in order to develop and improve health economic models to generate insight in the whole value of diagnostics and develop policy and regulatory recommendations. In addition, efficient clinical algorithms and user requirement specifications of tests will be developed fuelling the medical and technological value of CA-ARTI diagnostics. The value of diagnostics will be tested and demonstrated in a unique pan-European clinical and laboratory research infrastructure allowing for innovative adaptive trial designs to evaluate novel CA-ARTI diagnostics. Close and continuous interaction with the VALUE-Dx multi-stakeholder platform provides for optimal alignment of VALUE-Dx activities with stakeholder opinions, expert knowledge and interests. A variety of dissemination and advocacy measures will promote wide-spread adoption of clinical and cost-effective innovative diagnostics to achieve more personalized, evidence-based antibiotic prescription in order to transform clinical practice, improve patient outcomes and combat AMR.

Strongly associated with the epidemics of obesity and type 2 diabetes that are testing healthcare systems worldwide, Non-Alcoholic Fatty Liver Disease (NAFLD) is an increasingly common cause of advanced liver disease that is characterized by substantial inter-patient variability in severity and rate of progression. It is currently assessed by liver biopsy, an invasive, costly and risky procedure. The lack of noninvasive biomarkers has hampered patient care and impeded drug development by complicating conduct of clinical trials.The overarching aim of LITMUS is to develop, robustly validate and advance towards regulatory qualification biomarkers that diagnose, risk stratify and/or monitor NAFLD/NASH progression and fibrosis stage. This will be achieved through a goal-oriented, tri-partite collaboration delivering a definitive and impartial evaluation platform for biomarkers, bringing together: (i) End-users of biomarker technologies (clinicians with expertise in NAFLD and the pharmaceutical industry)? (ii) Independent academics with expertise in the evaluation of medical test/biomarker performance? and (iii) Biomarker researchers and developers (academic or commercial). LITMUS has the demonstrable capability to fulfil the IMI call remit. Built upon foundations laid by the EU-funded FLIP/EPoS projects and long-established, successful scientific collaborations amongst many of Europe’s leading clinical-academic centres, LITMUS is at a unique advantage due to its existing large-scale patient cohorts, bioresources and multi-omics datasets. Consortium members are internationally recognised experts with substantial relevant expertise supporting the program’s clear focus on biomarker identification, validation and accelerating EMA/FDA qualification. Thus, LITMUS is powered to provide clarity on biomarker validity for NAFLD at scale and pace: supporting drug development and the targeting of medical care and limited healthcare resources to those at greatest need.

Natural Killer (NK) cells have a critical role in anti-cancer immunity and recently the influence of the microbiome in cancer immunotherapy was shown. Comprehending the complex interplay between the expression of NK cells ligands involved in immune evasion mechanisms and the microbiome is crucial for achieving immunotherapy success. Diffuse Large B Cell Lymphoma (DLBCL) and Follicular Lymphoma (FL) are two types of Non-Hodgkin Lymphomas (NHL) characterized by accumulating B lymphocytes in lymph nodes, and extranodal sites. DLBCL and FL usually show aggressive and indolent behavior respectively. DLBCL, includes the known subtypes germinal center B-cells (GCB) and activated B-cells (ABC), and, like the DLBCL-GCB subtype, FL have a germinal origin as well. The mechanism involved in the immune-microbiome interplay are not clearly understood, hampering the improvement of therapeutic possibilities. The objective of this study is to reveal the complex interplay between the NK cells and the microbiome in DLBCL and FL patients and harness its therapeutic potential. To achieve this, I will use single-cell RNA sequencing and flow cytometry to analyze the composition of NK cells dissociated from DLBCL and FL samples. Then, I will use correlative analyses to identify the NK ligands/receptors that are more expressed in patients with low diversity and high variability microbiome. Ultimately, I will address the impact of this correlation in the response to immunotherapy. The results will pave the way for patient risk stratification establishment and new treatment options approaches. Conducting this project at the Tumor Stroma Interactions (TSI) group will provide me a solid scientific basis as well as technical development for further progressing my scientific career.