SFB 1129:
Integrative Analysis of Pathogen – Replication and Spread
Subject Area
Biology
Chemistry
Medicine
Term
since 2014
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
Current projects
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01 - Deciphering receptor-ligand interplay during rapid motility of Plasmodium sporozoites
(Project Heads
Frischknecht, Friedrich
;
Spatz, Joachim P.
)
-
03 - Protection of malaria by haemoglobin S and C: A quantitative understanding of the cytoadhesion behavior
(Project Heads
Lanzer, Michael
;
Tanaka, Motomu
)
-
04 - Modeling the adhesion of malaria-infected red blood cells
(Project Heads
Lanzer, Michael
;
Schwarz, Ulrich
)
-
05 - HIV-1 capture and spread at nanoscopic resolution
(Project Head
Kräusslich, Hans-Georg
)
-
06 - Dynamics of events in HIV-1 replication
(Project Head
Müller, Barbara
)
-
08 - HIV-1 spread in complex cell systems
(Project Head
Fackler, Ph.D., Oliver T.
)
-
11 - Spatial and temporal coordination of RNA translation, replication and assembly in a membranous plus-strand RNA virus replication factory
(Project Heads
Bartenschlager, Ralf Friedrich Wilhelm
;
Höfer, Thomas
;
Rohr, Karl
)
-
13 - Impact of virus-induced oscillating stress response on host cell homeostasis and immune response induction
(Project Head
Ruggieri, Ph.D., Alessia
)
-
15 - Nanoscale characterization of integrin-virus interactions
(Project Heads
Cavalcanti-Adam, Elisabetta Ada
;
Grimm, Dirk
;
Spatz, Joachim P.
)
-
17 - Hepatitis E virus trafficking in polarized human pluripotent stem cell-derived hepatocyte-like systems
(Project Head
Dao Thi, Ph.D., Viet Loan
)
-
18 - Deciphering the regulation of Plasmodium falciparum replication
(Project Heads
Ganter, Markus
;
Portugal, Silvia
)
-
19 - Structural analysis of influenza protein-membrane interactions during entry
(Project Head
Chlanda, Petr
)
-
20 - Nuclear pore complex and genome organization as determinants of HIV-1 integration and transcription
(Project Heads
Beck, Martin
;
Lusic, Ph.D., Marina
)
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21 - The role of matrix maturation in HIV-1 infection and spread
(Project Head
Briggs, John
)
-
22 - The role of mechanosensing and antibodies for interactions of Plasmodium sporozoites with neutrophils in 3D environments
(Project Heads
Frischknecht, Friedrich
;
Selhuber-Unkel, Christine
)
-
23 - How insecticides impact malaria parasite infectivity
(Project Head
Ingham, Victoria
)
-
24 - Host cell determinants for establishment and reversal of HIV-1 latency
(Project Head
Mücksch, Frauke
)
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Z01 - Central Tasks
(Project Head
Kräusslich, Hans-Georg
)
-
Z02 - Correlative light- and electron microscopy
(Project Heads
Briggs, John
;
Funaya, Charlotta
;
Krijnse Locker, Ph.D., Jacomine
;
Schwab, Yannick
)
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Z04 - Advanced Tracking and Image Analysis
(Project Heads
Hamprecht, Fred A.
;
Rohr, Karl
)
Completed projects
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02 - Role of intra- and extra-cellular host miRNAs as regulators of Plasmodium liver stages
(Project Heads
Grimm, Dirk
;
Müller, Ann-Kristin
)
-
07 - Pathogen passage through the Nuclear Pore Complex
(Project Head
Lemke, Edward A.
)
-
09 - The assembly and spread of influenza virus
(Project Head
Briggs, John
)
-
10 - Membrane lipids and proteins in influenza replication and spread
(Project Heads
Brügger, Britta
;
Kräusslich, Hans-Georg
)
-
14 - Visualising reovirus infection in polarised epithelium: From touchdown to antiviral innate immune response
(Project Heads
Boulant, Steeve
;
Kräusslich, Hans-Georg
)
-
16 - Visualization of Hepatitis B Virus entry and spread
(Project Heads
Grimm, Dirk
;
Urban, Stephan
)
-
Z03 - Chemical biology tools for infectious diseases research
(Project Heads
Johnsson, Kai
;
Schultz, Carsten
)