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SFB 1129:  Integrative Analysis of Pathogen – Replication and Spread

Subject Area Biology
Chemistry
Medicine
Term since 2014
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Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 240245660
 
Microbial pathogens have a major impact on human health that may further increase in the future with newly emerging infectious diseases like the ongoing COVID 19 pandemic. Pathogens rely heavily on their host in order to multiply and spread successfully. The mutual interplay between pathogen and host determines the net outcome of an infection leading to either disease or pathogen control. Traditionally, studying pathogen-host interactions dissected molecular events in simplified and artificial cell culture models. Infections were generally studied in bulk rather than quantitatively assessing individual events. New technology for visualiza-tion of events at high temporal and spatial resolution, quantification of host and pathogen components at the single cell level, genetic and functional manipulation of pathogen and host factors even in primary cells, and novel culture systems closer to normal cell and organ physiology now enable us to investigate, what drives pathogenesis and to dissect underlying mechanisms. This is increasingly complemented by mathe-matical modelling approaches. Understanding the complex pathogen-host interactions in relevant systems is the central aim of SFB1129, focusing on important human viral and parasitic pathogens, for which we have long-standing expertise in Heidelberg. With new tools and experimental systems now mostly in hand, individual groups in the second SFB funding period focused on structural effects and on the dynamics and homeostasis of pathogen-host interactions, visualizing individual events, and analyzing them in biophysically defined complex 3D structures. Many SFB collaborations involved the same or a closely related pathogen, but projects can be grouped equally well according to the respective scale: (i) defined subcellular events, (ii) changes in cellular architecture and ho-meostasis, (iii) influence of complex multicellular and 3D-architecture, and (iv) analysis and reconstitution of relevant events in (semi-)synthetic systems. Important progress has been made for all pathogens and at all scales, as specified in the individual project reports and SFB-derived publications, including a large number of joint publications with up to five individual projects.The overall concept of SFB1129 will continue in the third funding period. The network will be strengthened by four new projects addressing malaria and HIV-1 (with four projects being completed at the end of the current period). Starting from the determination of individual events for defined pathogens, the long-term vision of SFB1129 remains to achieve an overarching view on the complete process of infection and spread in complex tissues and in vivo, allowing us to follow an individual pathogen on its journey through the cell, tissue and organism. This is already in reach for certain stages and pathogens, and we expect important further progress in the next funding period, but the ambitious overall goal clearly goes beyond SFB1129.
DFG Programme Collaborative Research Centres
International Connection United Kingdom

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