COLLECTIVE DYNAMICS Gabriela Gomes Principal Investigator PhD in Ma<strong>the</strong>matics, University of Warwick, UK, 1993 Post-doctoral Researcher, Ma<strong>the</strong>matics Institute, University of Warwick Wellcome Trust Research Training Fellow in Ma<strong>the</strong>matical Biology, Department of Biological Sciences, University of Warwick Principal Investigator at <strong>the</strong> IGC since 2002 We study collective phenomena, such as self-<strong>organisation</strong>, criticality, and pattern formation, arising from spatial and temporal constraints in physical and biological systems, with a current focus on infectious disease ecology and evolution. The central <strong>the</strong>me of our research <strong>de</strong>rives from a conceptual mo<strong>de</strong>l of partial immunity whose collective outcome - <strong>the</strong> reinfection threshold - un<strong>de</strong>rlies a phenomenological transition in epi<strong>de</strong>mic dynamics, with practical implications ranging from extreme geographical variability in <strong>the</strong> effect of vaccination programmes to <strong>de</strong>stabilised transmission favouring polymorphism in antigenically diverse pathogens. We are interested in refining concepts and methodologies by performing specific experiments in <strong>the</strong> laboratory and in natural populations. MOLECULAR EPIDEMIOLOGY OF MYCOBACTERIUM TUBERCULOSIS IN PORTUGAL: IMPLEMENTING AND ANALYSING A DATABASE We propose to genotype all <strong>the</strong> strains from sputum of smear positive pulmonary tuberculosis cases with recent methods based on <strong>the</strong> variability of mycobacterial interspersed repetitive units (MIRU) and variable number tan<strong>de</strong>m repeats (VNTR). A database that inclu<strong>de</strong>s mycobacterial genotype and clinical and <strong>de</strong>mographic information about patients will be implemented, constituting a valuable resource for molecular epi<strong>de</strong>miology studies, transmission mo<strong>de</strong>ls and applied research on mycobacterial evolution and pathogenesis. A total of 2286 isolates of M. tuberculosis DNA were genotyped for 90 SNPs. About 300 strains were genotyped in <strong>the</strong> first year and 743 strains were genotyped during <strong>the</strong> second year. In <strong>the</strong> last period of <strong>the</strong> project, 1239 more samples were inclu<strong>de</strong>d. Increasing <strong>the</strong> number of genotyped strains is our immediate goal and will allow us to infer on <strong>the</strong> genetic diversity of M. tuberculosis circulating in <strong>the</strong> Portuguese population. EXPLORING PATHOGEN DIVERSITY IN DISEASE EPIDEMIOLOGY AND VACCINE RESEARCH Viruses, bacteria and parasitic pathogens have evolved multiple strategies to eva<strong>de</strong> innate and acquired immune responses, facilitating transmission, allowing <strong>the</strong> establishment of persistent and recurrent infections, and often hampering <strong>the</strong> <strong>de</strong>velopment of effective vaccines. Antigenic variation of immune response targets is one such pathogen strategy that can only be confronted with <strong>the</strong> support of a highly specialised research programme combining basic and applied research. This is <strong>the</strong> <strong>the</strong>me of this project. The team integrates basic research in infection, population genetics, and ma<strong>the</strong>matical epi<strong>de</strong>miology, with a range of practical aspects of experimental <strong>de</strong>sign from <strong>the</strong> laboratory to <strong>the</strong> field. The overall research strategy is to unravel <strong>the</strong> molecular bases and epi<strong>de</strong>miological significance of immunity in or<strong>de</strong>r to gui<strong>de</strong> vaccine <strong>de</strong>sign and <strong>de</strong>ployment. GROUP MEMBERS João Sollari Lopes (Post-doc, started in April) Ana Isabel Franco (Post-doc, started in September) Cátia Ban<strong>de</strong>iras (Trainee, started in December) Delphine Pessoa (Trainee) Bruno Ceña (Trainee) Caetano Souto Maior Men<strong>de</strong>s (Trainee, started in October) COLLABORATORS José Pereira-Leal (IGC, Portugal) Isabel Marques (IGC, Portugal) Carlos Penha-Gonçalves (IGC, Portugal) Lounes Chikhi (IGC, Portugal) Ana Godinho (IGC, Portugal) Anabela Miranda (INSA - <strong>Instituto</strong> Nacional <strong>de</strong> Saú<strong>de</strong> Dr. Ricardo Jorge, Portugal) Ana Abecasis (CMDT-IHMT - <strong>Instituto</strong> <strong>de</strong> Higiene e Medicina Tropical, Portugal) Diogo Pinheiro (ISEG - <strong>Instituto</strong> Superior <strong>de</strong> Economia e Gestão, Portugal) Raquel Sá-Leão (ITQB - <strong>Instituto</strong> <strong>de</strong> Tecnologia Química e Biológica, Portugal) Cláudia Co<strong>de</strong>ço (Fundação Oswaldo Cruz, Brazil) Alessandro Vespignani (Institute for Scientific Interchange, Italy) Lewi Stone (Tel Aviv University, Israel) Dirk Brockmann (Max Planck Institute Gottingen, Germany) Ronald Smallenburg (Grote Griepmeting, The Ne<strong>the</strong>rlands) John Edmunds (London School of Hygiene and Tropical Medicine, UK) Olof Nyrén (Swedish Institute for Infectious Disease Control, Swe<strong>de</strong>n) Marc van Ranst (Rega Institute for Medical Research, Belgium) Shlomo Havlin (Bar Ilan University, Israel) Stefano Merler (Fondazione Bruno Kessler, Italy) Daniele Miorandi (Center for Research and Telecommunication Experimentation for NETworked communities, Italy) Mário Silva (Faculda<strong>de</strong> <strong>de</strong> Ciências, Universida<strong>de</strong> <strong>de</strong> Lisboa, Portugal) Natalia Mantilla (Universidad Nacional Autónoma <strong>de</strong> México, México) Glória Teixeira (Universida<strong>de</strong> Fe<strong>de</strong>ral da Bahia, Brazil) FUNDING Fundação para a Ciência e a Tecnologia (FCT), Portugal Framework Programme 7, European Commission We compared key parameters un<strong>de</strong>rlying pneumococcal transmission in Portuguese and Finnish day care centres using a continuous-time event history mo<strong>de</strong>l in a Bayesian framework. We <strong>de</strong>veloped ma<strong>the</strong>matical and statistical mo<strong>de</strong>ls to elucidate <strong>the</strong> <strong>de</strong>sign of novel pre-clinical and clinical trials to assess intervention efficacy both in <strong>the</strong> laboratory and in <strong>the</strong> field. The new <strong>de</strong>signs are being refined using Drosophila-Wolbachia as an experimental system. EPIWORK - DEVELOPING THE FRAMEWORK FOR AN EPIDEMIC FORECAST INFRASTRUCTURE In recent years a huge flow of quantitative social, <strong>de</strong>mographic and behavioural data is becoming available, spurring <strong>the</strong> quest for innovative technologies that can improve <strong>the</strong> traditional disease-surveillance systems, providing faster and better localised <strong>de</strong>tection capabilities and resulting in a broad practical impact. IGC ANNUAL REPORT ‘11 RESEARCH GROUPS 40
Improved ICT techniques and methodologies support <strong>the</strong> inter-linkage and integration of datasets causing a qualitative change in <strong>the</strong> ways we can mo<strong>de</strong>l epi<strong>de</strong>mic processes. The EPIWORK project proposes a multidisciplinary research effort aimed at <strong>de</strong>veloping <strong>the</strong> appropriate framework of tools and knowledge nee<strong>de</strong>d for <strong>the</strong> <strong>de</strong>sign of epi<strong>de</strong>mic forecast infrastructures. The research consi<strong>de</strong>rs most of <strong>the</strong> much-nee<strong>de</strong>d <strong>de</strong>velopment of mo<strong>de</strong>lling, computational and ICT tools. We have focused on two specific project <strong>de</strong>liverables: 1. Mo<strong>de</strong>ls of disease transmission un<strong>de</strong>r seasonality and o<strong>the</strong>r external drivers; 2. Mo<strong>de</strong>ls of spread, impact and evolution of vector-borne pathogens, including <strong>the</strong> <strong>de</strong>mography and ecology of host species. IGC ANNUAL REPORT ‘11 RESEARCH GROUPS 41