The Instituto de Medicina Molecular João Lobo Antunes (iMM) is a leading European institute in basic biomedical research, now establishing a pioneering Centre of Excellence in human-centred clinical and translational research in Portugal. Research at iMM increasingly requires analysing large volumes of molecular, phenotypic and clinical data but its development is constrained by the national scarcity of experts in biomedical data science. BIOMICS is therefore set on iMM’s strong data-driven research and innovation (R&I) model and investment on the digital transformation of biomedical and clinical research. BIOMICS aims at: 1) leveraging iMM’s excellence in biomedical data science by implementing joint research projects with the partner institutions, strengthening existing interactions and promoting new ones, through staff exchanges, expert visits and joint lab retreats; 2) training a new generation of critically thinking and ethically aware researchers who are able to test scientific hypotheses on biomedical data and soundly interpret their results, through integration in international mentoring networks, facilitating conference and thematic course attendance, and organising on-site training; 3) enhancing international awareness and attract talent to iMM in data science, through mobility of researchers, targeted dissemination and communication activities, and on-site organisation of workshops and an international conference; 4) strengthening iMM’s entrepreneurial and innovation capacity, adapting it to the digital transformation of biomedical and clinical research, through professional technology transfer activities and synergies with the information technology industry. BIOMICS will sustainably leverage iMM’s timely R&I model by supporting the associated digital transformation, making iMM internationally competitive in biomedical data science. Moreover, BIOMICS will provide the partners with a platform for exploring the translational potential of their research.

Epileptogenesis and Epilepsy Network: from genes, synapses and circuitries to pave the way for novel drugs and strategies (EpiEpiNet) aims to promote collaborative multidisciplinary and translational research in epilepsy by enhancing effective knowledge transfer, exchange of best research practices, and the mobility of early stage researchers between the Instituto de Medicina Molecular João Lobo Antunes (IMM), and leading partners at the Academic Medical Centre at the University of Amsterdam, University of Rome La Sapienza and the Epilepsy Center of LUND University. EpiEpiNet encompasses reputed neuroscientists that have in common the aim of understanding of the basic mechanisms of epileptogenesis and their impact in synaptic and brain circuitry dysregulation, and to contribute to the development of innovative therapies against refractory forms of epilepsy. Specifically, we aim at 1) increase the scientific and technological innovation in epilepsy research in the whole network and at IMM in particular by interchange of ideas and researchers among the partners; 2) sustain the network activity beyond EpiEpiNet deadline by promoting joint grant applications and joint training of PhD students; 3) train of young researchers and promote their internationalisation; 4) increase the awareness of epilepsy among the caregivers and patients, by promoting joint discussions and targeted dissemination of EpiEpiNet activities and results. As tools, EpiEpiNet will promote 1) scientific meetings, 2) community-oriented debates, 3) thematic and hands-on workshops and summer schools, 4) short term and on-site training visits in and out IMM for scientific and technology transfer between partners. The added value of EpiEpiNet will easily be spread to the University of Lisbon and to the Portuguese community, due to the existing interactions with the Mind-Brain College of the University of Lisbon, with the national neuroscientific community, and with patient and caregiver organizations.

Viruses that infect the brain and other parts of the central nervous system are a worldwide threat of terrible dimensions. Viruses such as Zika, Dengue, Chikungunya, HIV or measles, for instance, and more recently the Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are responsible for thousands of victims severely impaired at neurological level each year in the world. One of the most recent large scale threats in this domain was a Zika virus outbreak in South America. Zika virus, like Dengue virus or Chikungunya virus, is spread mainly by mosquitos of the genus Aedes. While Dengue and Chikungunya viruses, as many others, might causes diseases with severe neurological disorders, Zika virus is much more dreadful in this regard. When a pregnant woman is infected, the virus is able to translocate the blood-placental barrier and then the developing blood-brain barrier of the foetus, causing microcephaly and serious neurological disorders to newly born babies. Although co-infections with Aedes-borne viruses, such as the above mentioned Zika, Dengue and Chikungunya viruses, are likely because several viral species coexist in the same vector, the classical drug development strategies completely overlook this striking reality. Moreover, additional co-infections with HIV, SARS-CoV-2 and measles virus, using other routes of infection, are also possible. A drug able to target a very large spectrum of viral species is urgently needed. Importantly, this drug must be able to traverse the blood-brain barrier and reach the viruses accumulated in the brain. NOVIRUSES2BRAIN is a project that aims at finding and selecting drug leads that are both efficacious and able to translocate the blood-placental and blood-brain barriers so that Zika, Dengue, Chikungunya and other viruses, such as the recently discovered SARS-CoV-2 can be targeted across barriers, including during pregnancy. The project gathers the expertise of medicinal chemists, biochemists, drug development specialists and virologists to create drug leads able to clear all viral species from brain simultaneously.

Antibiotic resistance (AMR) is a major public health issue, with 5 million deaths in 2019 linked to AMR worldwide. These numbers are comparable to the toll of the SARS-CoV-2 pandemic. Without new solutions, AMR is projected to soon become one of the leading causes of death in the EU. Addressing this challenge requires the development of new, effective antibiotics, but this alone is not sufficient due to the rapid evolution of bacteria. Understanding the drivers and mechanisms of AMR is vital to delay or reverse resistance in both existing and new antibiotics, especially since no new broad-spectrum antibiotics have been developed since the 1990s and their development is a lengthy process with high attrition rates. The ENDAMR doctoral network aims to better equip researchers in Europe to understand and develop new strategies to tackle AMR. WP1 focuses on how AMR affects the fitness of pathogenic bacteria in the gut microbiome, aiming to identify microbiome characteristics that predispose to AMR infections and to explore microbiome-based interventions. WP2 examines AMR acquisition via horizontal gene transfer, investigating evolutionary pathways, host genetics, environmental factors, dissemination, and AMR reservoirs. WP3 is dedicated to understanding the frequency, mechanisms, and clinical implications of antibiotic resistance, with a particular focus on the less studied aspects of heteroresistance and tolerance, and to developing diagnostic tools and predictive models. WP4 explores the combination of antibiotics to enhance treatment outcomes and potentially prevent or reverse AMR, based on understanding the interplay of resistance mechanisms. ENDAMR will also prepare doctoral candidates for various career paths beyond academia, including teaching, science communication, and entrepreneurship. Candidates will gain transferable skills and learn from industry role models, equipping them to make significant contributions to solving the AMR crisis.

Malaria remains the most serious parasitic infectious disease, killing one child every two minutes. Plasmodium infection starts when the female Anopheles mosquito injects sporozoites into the skin of the vertebrate host. All Plasmodium species go through a phase of replication inside nucleated cells prior to infecting red blood cells and causing malaria, however, only mammalian-infectious parasites target the liver and replicate inside hepatocytes at an extraordinary rate to generate tens of thousands of erythrocyte-infectious merozoites. Avian and reptile malaria parasites, in contrast, infect macrophages near the bite site and differentiate into only dozens of erythrocyte-infectious merozoites. The reason behind the high replication rate achieved by mammalian-infectious parasites inside hepatocytes, key to guarantee the establishment of infection by overcoming the bottleneck of malaria transmission caused by a low sporozoite inoculum, remains utterly unexplored. The hypothesizes of this proposal is that the explanation for this lies in the uniqueness of the mammalian hepatic methionine metabolism bestowed by the mammalian liver-specific methionine adenosyltransferase (MAT1) enzyme and its capacity for generating unlimited amounts of S-adenosylmethionine. In agreement with this hypothesis, preliminary data show that Plasmodium’s high replication rate inside hepatocytes relies on the host liver-specific MAT1. By using a combination of genetic, cellular and molecular approaches I will decipher how the liver-specific methionine metabolism present in hepatocytes is hijacked and used by the parasite to achieve such high replication rates and assess the competence of the liver-specific MAT1 in sustaining Plasmodium replication. This proposal has the potential to establish a novel paradigm on how the environment and the resources provided by the host have evolutionarily influenced Plasmodium’s life cycle and will pave the way for new therapeutic targets against malaria.