[3C] Cells, Computers & Clinics

Søren Brunak is a leading pioneer in the biomedical sciences through invention and introduction of new computational strategies for analysis of biomedical data for use in molecular biology, medicine and biotechnology. His main achievements can be divided into two categories: 1) new, advanced bioinformatics and systems biology techniques, and 2) discovery of biological mechanisms, revealed by the use of these methods in a wide range of biological systems.

Søren Brunak has been working within bioinformatics and computational biology since mid-1980s. In the early data-poor period Søren Brunak pioneered the introduction of new computational strategies for analysis of biological data of relevance in molecular biology, medicine and biotechnology – in particular machine learning techniques. In 1993 Søren Brunak became the founding Director of the Center for Biological Sequence Analysis (CBS) at the Technical University of Denmark (DTU), heading a multi-disciplinary research group of molecular biologists, biochemists, medical doctors, physicists, and computer scientists.

In 2007 Søren Brunak became one of the founding research directors at the Novo Nordisk Foundation Center for Protein Research at the University of Copenhagen. His program for Disease Systems Biology combines molecular level systems biology and the analysis of phenotypic data from the healthcare sector. In 2011 Søren Brunak was also one of the founders of the Novo Nordisk Foundation Center for Biosustainability at DTU, where he led the Section for Metagenomic Systems Biology until 2013. He continues to be affiliated professor at DTU (DTU Bioinformatics) as well as at Copenhagen University Hospital (Rigshospitalet).

The impact of Brunak’s research is in particular a consequence of his ability to combine scientific disciplines in novel ways, including computer technology (hardware and software), physics, biology, biomedical and biotechnological insights. His multi-disciplinary approaches, where concepts from different areas have been combined, have led to advances in the understanding of the function of biological systems, and thereby fundamentally improved the possibilities for control of disease via novel intervention strategies, and enhancement of health in general. Søren Brunak has been a member of the Royal Swedish Academy of Sciences since 2016, a member of the Royal Danish Academy of Sciences and Letters since 2004 and a member of the European Molecular Biology Organization since 2009.

Søren Brunak has published close to 300 papers in international peer reviewed scientific journals (excluding proceedings), co-authored four books, three proceedings and edited books.

Akiko Iwasaki, Ph.D., is a Sterling Professor of Immunobiology and Molecular, Cellular, and Developmental Biology at Yale University, and an Investigator of the Howard Hughes Medical Institute. She received her Ph.D. from the University of Toronto in Canada and her postdoctoral training from the National Institutes of Health. Her research focuses on the mechanisms of immune defense against viruses at the mucosal surfaces, and the development of mucosal vaccine strategies. She is the co-Lead Investigator of the Yale COVID-19 Recovery Study, which aims to determine the changes in the immune response of people with long COVID after vaccination. Dr. Iwasaki also leads multiple other studies to interrogate the pathobiology of long COVID, both in patients, and through developing animal models of long COVID. Dr. Iwasaki was elected to the National Academy of Sciences in 2018, to the National Academy of Medicine in 2019, to the European Molecular Biology Organization in 2021, and to the American Academy of Arts and Sciences in 2021.

Mervyn Singer is professor of intensive care medicine at University College London. His primary research interests are sepsis and multi-organ failure, infection, shock and haemodynamic monitoring. Funding for these activities primarily comes from the Wellcome Trust, Medical Research Council, European Union and National Institute for Health Research.

He developed an oesophageal doppler haemodynamic monitor; multiple studies have shown its use to improve outcomes after major surgery and reduce length of stay. He co-developed the UCL Ventura CPAP device to support the breathing of COVID-19 patients in respiratory failure which has been widely distributed around the NHS and to many other countries. He has led on a number of important multi-centre trials in critical care, authored various papers and textbooks including the Oxford Handbook of Critical Care, now in its third edition, and is current chair of the International Sepsis Forum.

He co-chaired the Sepsis-3 Definitions International Task Force that redefined sepsis in 2016; the resulting paper has had >three million views and is one of the most heavily cited in the scientific literature over the past five years. He was the first UK intensivist to be awarded senior investigator status by the National Institute for Health Research, and to be invited to give plenary lectures at the European and US Intensive Care Congresses.

Cecilia Domínguez Conde is a Group Leader at the Population & Medical Genomics programme of the Genomics Centre. After training as a pharmacist in the University of Seville, Cecilia went on to do a PhD in Immunology at the Research Centre for Molecular Medicine (CeMM) in Vienna where her work focused on dissecting the genetic cause of molecularly undiagnosed primary immunodeficiencies using exome sequencing. In 2019 Cecilia joined the Teichmann lab at the Wellcome Sanger Institute where her focus has been to dissect the diversity of human immune cell types across lymphoid and non-lymphoid tissues as part of the Human Cell Atlas initiative. Her research group at HT uses cutting-edge genomic technologies to study developmental immunology.

Associate Professor of Applied Physics and Head of the Complex Multilayer Networks (CoMuNe) Lab at the Department of Physics and Astronomy 'Galileo Galilei' of the University of Padua.

My research activity is at the edge of theoretical, experimental, and computational aspects of statistical physics of complex systems, where theory is used to make hypotheses about empirical phenomena in biological, ecological, socio-technical, and socio-ecological sciences, which are then validated in real (sometimes massive) data sets. To date, I have applied such tools to:

• the interactome of humans and several other organisms
• the human, macaque and C. Elegans connectomes
• a variety of socio-ecological and socio-technical ecosystems
• the Internet and the Dark Web
• a variety of transportation infrastructures, including the global airport network, rail networks, road networks, and multimodal urban transportation means

A (non-exhaustive) list of my current activities includes:

• the mathematical formulation of multiplex networks, the study of their structure and of dynamical processes on such systems, the study of their resilience to random or targeted perturbations
• the formulation of an appropriate statistical physics/information theory of complex networks
• the formulation of a geometry of network-driven processes
• the application of advanced mathematical techniques to reduce the complexity of networked systems
• the functional representation of a system from the measurement of signals produced by its units, with application to the human brain, human interactome, climate change, and social systems

I also find enough time to investigate hidden structural and dynamical patterns in complex real and virtual time-varying networks, with particular attention to social, biological, and economic systems. Indeed, I develop models and simulations for human mobility, the spreading of epidemics, and of information in real-world social networks.

The research group, led by Jocelyne Demengeot, is concerned with those properties of the immune system that guarantee tissue integrity as well as tolerance to commensals and food antigens while maintaining the ability to mount efficient responses to infectious agents and some tumours. Rooted in this thematic is also the biological puzzle of phenotypic heterogeneity, the challenge of personalised medicine.

The research group approach the cellular and molecular bases of immune regulation through the analysis of various mouse models, notably of spontaneous or induced autoimmune and immuno-pathological inflammation.

Closer to the clinic, they interrogate the biological basis of the most extreme manifestations in autoimmune diseases and of the variable efficacy of immunotherapies.

Luis M. Rocha is the George J. Klir Professor of Systems Science at the Thomas J. Watson College of Engineering and Applied Science (Department of Systems Science and Industrial Engineering), Binghamton University (State University of New York), where he leads the Complex Adaptive Systems and Computational Intelligence (CASCI) lab. He is also director of the Center for Social and Biomedical Complexity, between Binghamton University and Indiana University, Bloomington. He has been the director of the NSF-NRT Interdisciplinary Training Program in Complex Networks and Systems, and Professor of Informatics in the Luddy School of Informatics, Computing, and Engineering at Indiana University, where he was a member of the advisory council of the Indiana University Network Science Institute, and core faculty of the Cognitive Science Program. Dr. Rocha is a Fulbright Scholar and is Principal Investigator at the Instituto Gulbenkian da Ciencia. He has been a Visiting Professor a the Center for Theoretical Physics at the Aix-Marseille University, France as well as the Neuroscience Program, at the Champalimaud Foundation and the NOVA School of Business and Economics in Portugal. His research is on complex networks & systems, computational & systems biology, and computational intelligence. He received his Ph.D in Systems Science in 1997 from the State University of New York at Binghamton. From 1998 to 2004 he was a permanent staff scientist at the Los Alamos National Laboratory, where he founded and led a Complex Systems Modeling Team during 1998-2002, and was part of the Santa Fe Institute research community. He has organized major conferences in the field such as the Tenth International Conference on the Simulation and Synthesis of Living Systems (Alife X), the Ninth European Conference on Artificial Life (ECAL 2007), and Complex Networks 2019. He has published many articles in scientific and technology journals, and has been the recipient of several scholarships and awards. At Indiana University, he has received the Indiana University, School of Informatics & Computing, Trustees Award for Teaching Excellence in 2006 and 2015 after developing the complex systems training program and syllabi for several courses.

Gene regulation is central to all biology. RNA molecules, with their ability to both encode information and exert catalytic activities, play a key role in the regulation of gene expression.

Our group aims to discover molecular pathways and mechanisms implicating RNA in human health and disease. More specifically, we study RNA splicing and its role in the regulation of gene expression in cancer and genetic diseases, and we are exploring new medical applications for RNA.

Research Areas:

• Cell Biology
• Genomics
• RNA Splicing
• RNA in Disease
• Epigenetics

Dulce Brito licenciou-se em Medicina na Faculdade de Medicina da Universidade de Lisboa, em 1982. Especializou-se em medicina interna, em medicina intensiva e em cardiologia, tendo feito a maior parte da sua aprendizagem e treino nestas áreas no Hospital Universitário de Santa Maria (Lisboa, Portugal). Posteriormente, desenvolveu na mesma Faculdade a sua tese de Doutoramento na área de Miocardiopatias, adquirindo o grau de Doutor (PhD.) em 2007. Desde então é Professora Auxiliar Convidada de Cardiologia na Faculdade de Medicina da Universidade de Lisboa.

Dr. Peyman Sardari Nia is a Senior Consultant Cardiothoracic Surgeon in the Department of Cardiothoracic Surgery at Maastricht University Medical Center, The Netherlands, where he specializes in minimally invasive cardiothoracic surgery. He is also the leader and initiator of the mitral valve program in Maastricht. Dr. Sardari Nia is actively involved in the European Association for Cardio-Thoracic Surgery (EACTS) and founder and director of the EACTS courses in minimally invasive techniques for adult cardiac surgery and endoscopic mitral valve repair.

Meet the expert: https://www.youtube.com/watch?v=c6GX48k9lq0&t=40s

Sylvia Knapp, MD, PhD, is Professor of Infection Biology at the Medical University of Vienna. Sylvia studied Medicine in Vienna and Berlin, is a board-certified internist and obtained her PhD at the University of Amsterdam. In  2006, she joined CeMM as a Principal Investigator and until recently, she continued her clinical duties while  also running her own lab. Sylvia’s research focuses on the innate immune response to infections in general, focusing specifically on the comprehensive repertoire of macrophage functions in health, development, and disease. Her group discovered the molecular mechanisms linking hemolysis and susceptibility to infections. Her latest research is directed towards the interplay of immune cells regulating lung tissue homeostasis in health and disease. Sylvia is highly committed to bridging academic medicine and basic science. She is a member of the Academia.Net circle of excellent female scientists and was elected corresponding member of the Austrian Academy of Sciences in 2014. In 2018, Sylvia was appointed to the University Board of the Medical University of Graz and elected vice president of the Ludwig Boltzmann Society.

Before joining the University of Malta’s Dept. of Applied Biomedical Sciences, Dr. Scicluna held a tenured position at the respected Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands, as Assistant Professor in the Department of Epidemiology and Data Science, as well as faculty position in the Center for Experimental Molecular Medicine, Amsterdam Institute of Infection and Immunity. Dr. Scicluna’s work focuses on clinical immunogenomics and immunobiology in the context of critical illness due to severe infections, non-infectious aetiologies, and cancer. Dr. Scicluna’s work is published in several prestigious international journals that include Nature, Nature Immunology, Nature Reviews Immunology, Journal of the American Medical Association (JAMA), Lancet Respiratory Medicine, Cell Metabolism, and the American Journal of Respiratory and Critical Care Medicine. Dr. Scicluna is an active member of international consortia, including a Sepsis Subclasses consortium, and the Combatting Antimicrobial Resistance in Europe (COMBACTE) consortium (https://www.combacte.com/stories/brendon-scicluna/).
He read for his undergraduate degree at St. John’s University and the College of St. Benedict, Collegeville, Minnesota, USA, which he followed with an M.Sc. from the University of Malta. He then joined the University of Amsterdam’s Academic Medical Centre to read for his Ph.D.
Dr. Scicluna has successfully coordinated and executed several population-scale clinical genomics studies, which have culminated in various high impact publications, as well as candidate biomarkers with clinical implications. Dr. Scicluna’s work has been highlighted as a key bridge to fulfill the promise of personalized genomics and precision medicine in the context of infectious diseases and intensive care medicine. He has collaborated with several respected research groups in the USA and Europe on topics that include sepsis, neuropathology, disease tolerance and cancer. He is also a very much sought-after lecturer by various conferences and institutes abroad.

Dr. Scicluna is currently working within the framework of the Malta Council for Science and Technology (MCST) COVID-19 RnD fund - project “TargetID” (https://www.um.edu.mt/projects/targetid).

Jesús is an associate professor (Profesor Titular) in the Department of Condensed Matter Physics of the University of Zaragoza (Spain). He leads the Group of Theoretical & Applied Modeling (GOTHAM lab) at the Institute of Biocomputation and Physics of Complex Systems (BIFI).

The primary goal of GOTHAM lab gravitates around theoretical and computational aspects of complex systems, with main focus on data-driven modeling of empirical systems and the analysis of collective behaviors.

Our interests are widely interdiciplinar and cover scientific fields such as Epidemiology, Ecology, Systems biology, Neuroscience and Social sciences. Our main modeling tools require the use of techniques from Statistical and Computational physics, Nonlinear dynamics, Network Science and Big Data analysis.

In a nutshell, our aim is to shed light on the basic mechanisms and interactions that shape the behavior of real-world complex systems.

Erin Tranfield obtained her PhD at the University of British Columbia (Canada), did a postdoc at NASA Ames Research Center (USA) and another at the European Molecular Biology Laboratory (EMBL-HD, Germany). In 2013, she moved to the Instituto Gulbenkian de Ciência to build a biological electron microscopy facility. Today her and her dedicated team support the research of Portuguese-based scientists, aiming to answer a diverse array of biological and material science questions. Erin has more than 20 years of biological electron microscopy experience with expertise in room temperature EM, cryo-immobilization, electron tomography, and CLEM. She is the President of the Portuguese Microscopy Society, the co-chair of the ESA Topical Team on Celestial Dust Toxicity, a member of the EMBL Alumni Board, part of numerous evaluation panels and she recently joined the Editorial Board of Wiley Analytical Science. In 2020 Erin founded the TechEM Seminar Series which aims to bring advanced technical seminars to EM Facility staff all over Europe and Asia.

The Innate immunity and inflammation laboratory works on two different topics: innate immunity and inflammation. Their focus on innate immunity is centered on the study of antigen cross-presentation mechanisms and the immunobiology of dendritic cells.

Effective immune responses against tumor antigens that are not endogenously expressed by dendritic cells (DCs) and against viruses that do not infect antigen presenting cells (APCs) require extracellular antigens to stimulate CD8+ T cells via the MHC I pathway through a process poorly characterized at the molecular level known as antigen cross-presentation.

Researchers are using a series of systematic genetic approaches to identify the molecular machinery involved in antigen cross-presentation. In addition, we want to explore antigen cross-presentation as an early immune-regulatory checkpoint in the control of CD8+ T cell priming by dendritic cells, to find drugs that inhibit negative regulators of this process, as they are likely to improve the generation of effective T cells responses against tumors and are good candidates for novel adjuvant therapies for cancer treatment.

The second theme of the laboratory relates to inflammation.

Severe sepsis remains a poorly understood systemic inflammatory condition with high mortality rates and limited therapeutic options outside of infection control and organ support measures.

Based on their recent discovery in mice showing that anthracycline drugs prevent organ failure without affecting the bacterial burden in a model of severe sepsis, we propose that strategies aimed at target organ protection have extraordinary potential for the treatment of sepsis and possibly for other inflammation-driven conditions.

However, the mechanisms of organ protection and disease tolerance are either unknown or poorly characterized.

The central goal of this research program is to identify and characterize novel cytoprotective mechanisms, with a focus on DNA damage response dependent protection activated by anthracyclines as a window into stress-induced genetic programs leading to tissue protection.

Immunity evolved in multicellular organisms to limit the potential negative impact resulting from continuous exposure to microbes. Innate and adaptive components of the immune system are endowed with the capacity to sense and target pathogenic microorganisms for containment, destruction or expulsion as the means to preserve organismal homeostasis and fitness. Resistance to infection refers to the output of these immune functions.

Multicellular organisms also evolved another defense strategy that preserves organismal homeostasis and fitness without exerting a direct negative impact on microorganisms. This defense strategy, referred to as disease tolerance, relies on evolutionarily conserved stress and damage responses that limit the extent of metabolic dysfunction and damage imposed on parenchyma tissues, either directly by pathogenic microorganisms or indirectly by immune-driven resistance mechanisms.

The overall aim of the Inflammation Laboratory is to identify and characterize these stress and damage responses which confer tissue damage control and establish disease tolerance to infection.

The central hypothesis tested is that a functional interplay between immune-driven resistance mechanisms, and stress and damage responses acting in parenchyma tissues, exists to limit, counter and repair the pathogenic effects of infection.

Understanding the cellular and molecular mechanisms governing this network of interactions and responses should be transformative in our understanding of host-microbe interactions, with direct impact on the treatment of infectious diseases.

The Cellular Immunology Lab studies mechanisms able to induce and maintain immune tolerance. We study diseases, or animal models of human pathologies, where the immune system has an inappropriate action, such as in autoimmunity, transplantation or allergy.

We aim to reprogram the immune system, inducing the expansion of regulatory T cells capable of reinstating the tolerance state. We always strive to validate our experimental results in collaboration with clinical scientists.

After completing a PhD in clinical immunology and residency in internal medicine in 2015, I have been dedicated to Critical Care. I have been involved and coordinated several outcome research projects, developed, and became responsible for critical care teaching at Medical School of the University of Lisbon and pursued translational studies as a researcher at Instituto de Medicina Molecular João Lobo Antunes. Since my fist days as a critical care physician, I have been always interested in lung injury and recovery and started an ongoing project in this field which was also adapted during Covid-19 pandemic. I am now particularly interested in understanding the recovery from critical illness, and patterns of recovery after ARDS and sepsis.

Elisa has a PhD in molecular medicine with the focus on the innate immune system from the Jena University Hospital (Germany) and is currently a PostDoc in the Inflammation Lab led by Miguel Soares at the IGC. Her interests are to uncover molecular mechanisms of infectious diseases which can serve as the basis for new treatment strategies as an alternative to antibiotic use. Her research focus lies within the interaction of innate immune cells, e.g. macrophages and parenchymal tissues, in the context of sepsis.

Rion has a PhD in the Complex Networks & Systems track of Informatics from Indiana University (IN, USA). His interests lie in improving human health, a multi-leveled complex adaptive system of interacting chemical components at the micro, and whole individuals at the macro level. His research focuses towards understanding this system, all the way from biochemical regulation and systems biology, to individual, social, and population level behaviors, using primarily methods from complexity science and its sub-fields of data and network science; supported by inherently heterogeneous data, including Boolean networks, genomics, electronic health records, and even social media.

Katharina holds a PhD in biochemistry/molecular immunology from UCL/CRUK and is interested in molecular medicine, having worked in clinical and basic research on rare primary immunodeficiency patients (CeMM Vienna) as well as on systems biology approaches. Her current focus is on molecular and metabolic mechanisms of host tolerance to sepsis with Luis Moita at IGC.

David Soriano-Paños holds a PhD in Physics from University of Zaragoza and currently works as an independent postdoctoral researcher at IGC. His research is focused on the characterization of complex systems through the lens of statistical physics, nonlinear dynamics and network science, especially focusing on the interplay between human mobility and the spread of communicable diseases.

Dora holds a PhD in Molecular Biology (KCL, UK). She has worked in stem cells and biomaterials for tissue regeneration, DUB enzymes germane to cancer as drug targets in a drug discovery programme and anthracyclines in the context of infectious diseases, such as sepsis. She is currently the Lab Manager in Luís Moita’s lab at IGC.

Tiago is a cardiac surgery resident and a PhD student in the Innate Immunity and Inflammation laboratory at IGC, working as a physician and a researcher. He is interested in clinical and basic research, particularly on organ dysfunction and host tolerance. His research focus is now the metabolic mechanisms of systemic inflammatory response syndrome after cardiac surgery, and how their modulation can induce postoperative tissue protection and host tolerance.

Sílvia is a Senior Research Technician in the Inflammation Lab led by Miguel Soares at the IGC. She holds a post-graduation in Parasitology. Since 2005 she works with mouse models and is responsible for the management of mouse colonies and all the mice generated for experimental purposes at the Inflammation Lab, with critical contributions to several publications.

Jess is a post-doctoral researcher working in the Inflammation Lab with Dr. Miguel Soares, at the IGC. Her research interests stem from a desire to understand the molecular mechanisms through which bacteria interact with each other and their hosts to reciprocally modulate each other’s physiology in health and disease. She completed her PhD at Imperial College, London, in Salmonella-macrophage interactions, investigated mechanisms of intra- and inter-bacterial signalling in the mammalian gut microbiota, and is now looking at how host glucose metabolism affects Salmonella virulence during systemic infection.

Is working on membrane protein biogenesis using influenza virus replication as a model, to tease apart self-organizing principles that govern protein targeting at the ER. To answer these questions, specific protein-protein interactions and targeting steps need to be framed in a larger proteostatic frame using proteomics approaches. He is currently pursuing a PhD in Maria-João Amorim’s lab, in collaboration with Colin Adrain’s lab.