Complementary expertise<\/strong><\/h2>\n\n\n\nTaking further steps towards understanding how pathogens hijack cellular machinery and wreak havoc on human health needs large collaboration efforts. Wilmanns and colleagues wanted to take this a step further by bringing together computational, structural and wet lab researchers in a single building with access to state-of-the-art infrastructures. The opening of the CSSB building in June was the realisation of a vision first set out a decade ago.<\/p>\n\n\n\n
CSSB is a collaboration of presently nine academic partners from North Germany, each active in different areas of infection biology research. The partners are represented by one or more research groups within the new building on the DESY campus in Hamburg, and together they will use a combination of structural and systems biology approaches to unravel the fundamental mechanisms of how pathogens infect their hosts. \u201cIt is not enough to understand the structure of the miniscule tools that a pathogen uses to infect its host, for example,\u201d says Wilmanns. \u201cIn order to eventually inform the development of urgently needed new drugs, we need to understand how the tools are built, what other molecules are required to build it and how they all interact with each other. We need to throw all the knowledge and know-how we have together to understand this whole process.\u201d<\/p>\n\n\n\n
One of EMBL\u2019s representatives within the CSSB is group leader Christian L\u00f6w<\/a>. He was among the first to move into the new building after its inauguration in June. His cosy office on the second floor of the building looks out to a patch of woodland at the heart of the DESY campus. L\u00f6w has been heavily involved in shaping the concept and structure of CSSB since he joined EMBL three years ago<\/a>, an experience he has very much appreciated. Now it\u2019s time to focus on the science.<\/p>\n\n\n\n![\"EMBL](\"https:\/\/news.embl.de\/wp-content\/uploads\/2017\/11\/Loew_EMBL_620x380-1.jpg\")
EMBL representative and CSSB group leader Christian L\u00f6w. IMAGE: CSSB<\/figcaption><\/figure><\/div>\n\n\n\n\u201cCSSB is unique in that researchers have access to a simply breath-taking range of different techniques to study the structural details of molecules and cells at different scales of resolution,\u201d L\u00f6w continues. \u201cWe have the tools to zoom in to the position of an individual atom within a cellular protein using X-ray crystallography and electron microscopy. We are also able to zoom out and see how components interact within cells and organisms using the latest fluorescence microscopy methods. We want to piece all this information together to get a complete picture of what happens during infection across time and resolution scales.\u201d<\/p>\n\n\n\n
State-of-the-art<\/strong><\/h2>\n\n\n\nCSSB will use bioinformatics analyses to interpret those snapshots within the context of how infections operate within a host. And the new building is perfectly situated to make use of the immense research infrastructures on its doorstep. \u201cThe parallel X-ray beams provided by the EMBL beamlines at the PETRA III synchrotron on campus are extremely intense and precise \u2013 ideal for studying tiny delicate crystals of large proteins,\u201d explains Wilmanns. \u201cThe development of the CSSB will enable structural biologists to further focus their collective expertise in order to get the most out of these incredible infrastructures.\u201d<\/p>\n\n\n\n
![\"The](\"https:\/\/news.embl.de\/wp-content\/uploads\/2017\/11\/BUILDING_EMBL_620x380-1.jpg\")
The Centre for Structural Systems Biology (CSSB), located on the DESY campus in Hamburg<\/figcaption><\/figure><\/div>\n\n\n\nThe building will also host four core facilities using state-of-the-art technologies and equipment. Protein characterisation and crystallisation facilities at EMBL next door have been expanded and upgraded in order to serve both EMBL and CSSB. An advanced light and microscopy facility will be run in cooperation with leading microscope manufacturer Leica microsystems. A protein production facility is in the process of being set up. In addition, an in-house electron-microscopy facility will also be available, with four microscopes set to come online before the end of the year.<\/p>\n\n\n\n
Interdisciplinary collaboration<\/strong><\/h2>\n\n\n\nL\u00f6w is fascinated by membrane transporters. These large protein complexes sit astride the cell membrane and regulate the traffic passing in and out of the cell \u2013 letting important nutrients in and keeping nasty invaders out. Their size and shape mean they are tricky to study using methods such as X-ray crystallography alone. L\u00f6w has spent the last few years optimising methods for handling these proteins for crystallography experiments. \u201cNow we understand how to work with these proteins we will help other CSSB groups optimise their protocols as well as widening our horizons to look at how they are regulated and interact within the cell,\u201d he explains. Working together with CSSB group leader Tim Gilberger of the Bernhard-Nocht-Institute for Tropical Medicine, L\u00f6w plans to investigate a membrane complex that allows the malaria parasite to invade the red blood cells of a human host.<\/p>\n\n\n\n
\u201cThis membrane complex is fascinating,\u201d L\u00f6w explains. \u201cIt sits across multiple layers of the pathogen cell membrane and is very large. To visualise its atomic structure in high-resolution, we will use multiple techniques including crystallography and electron microscopy supported by Kay Gr\u00fcnewald of the Heinrich Pette Institute. The membrane complex is crucial for the survival of the malaria parasite, so a complete understanding of its structure and biology would enable us to design small molecules to block it, thereby halting the disease,\u201d says L\u00f6w.<\/p>\n\n\n\n
Even before groups moved into the building, interdisciplinary collaboration within the network developed during the CSSB\u2019s formation started bearing fruit. Thomas Marlovits, CSSB group leader from the University Hospital Hamburg Eppendorf, uses a range of structural biology methods to study groups of proteins called secretion systems that certain types of bacteria such as Salmonella<\/em> and E.coli<\/em> use to infect their host. Wilmanns teamed up with Marlovits to study a secretion system found in the tuberculosis pathogen Mycobacterium<\/em>. Using a combination of small-angle X-ray scattering and electron microscopy techniques complemented by biochemical and biophysical studies, the groups were able to reveal the unusual shape of the system and the unexpected position of the complex within the Mycobacterium<\/em> cell membrane. \u201cThe results advance our knowledge of how tuberculosis pathogens function,\u201d says Wilmanns. \u201cIt shows how powerful interdisciplinary studies can be for infection research.\u201d<\/p>\n\n\n\n CSSB is a joint initiative of ten research partners from northern Germany, including three universities and six research institutes.\n\n\n\n
\u201cCSSB is unique in that researchers have access to a simply breath-taking range of different techniques to study the structural details of molecules and cells at different scales of resolution,\u201d L\u00f6w continues. \u201cWe have the tools to zoom in to the position of an individual atom within a cellular protein using X-ray crystallography and electron microscopy. We are also able to zoom out and see how components interact within cells and organisms using the latest fluorescence microscopy methods. We want to piece all this information together to get a complete picture of what happens during infection across time and resolution scales.\u201d<\/p>\n\n\n\n
State-of-the-art<\/strong><\/h2>\n\n\n\nCSSB will use bioinformatics analyses to interpret those snapshots within the context of how infections operate within a host. And the new building is perfectly situated to make use of the immense research infrastructures on its doorstep. \u201cThe parallel X-ray beams provided by the EMBL beamlines at the PETRA III synchrotron on campus are extremely intense and precise \u2013 ideal for studying tiny delicate crystals of large proteins,\u201d explains Wilmanns. \u201cThe development of the CSSB will enable structural biologists to further focus their collective expertise in order to get the most out of these incredible infrastructures.\u201d<\/p>\n\n\n\n
The Centre for Structural Systems Biology (CSSB), located on the DESY campus in Hamburg<\/figcaption><\/figure><\/div>\n\n\n\nThe building will also host four core facilities using state-of-the-art technologies and equipment. Protein characterisation and crystallisation facilities at EMBL next door have been expanded and upgraded in order to serve both EMBL and CSSB. An advanced light and microscopy facility will be run in cooperation with leading microscope manufacturer Leica microsystems. A protein production facility is in the process of being set up. In addition, an in-house electron-microscopy facility will also be available, with four microscopes set to come online before the end of the year.<\/p>\n\n\n\n
Interdisciplinary collaboration<\/strong><\/h2>\n\n\n\nL\u00f6w is fascinated by membrane transporters. These large protein complexes sit astride the cell membrane and regulate the traffic passing in and out of the cell \u2013 letting important nutrients in and keeping nasty invaders out. Their size and shape mean they are tricky to study using methods such as X-ray crystallography alone. L\u00f6w has spent the last few years optimising methods for handling these proteins for crystallography experiments. \u201cNow we understand how to work with these proteins we will help other CSSB groups optimise their protocols as well as widening our horizons to look at how they are regulated and interact within the cell,\u201d he explains. Working together with CSSB group leader Tim Gilberger of the Bernhard-Nocht-Institute for Tropical Medicine, L\u00f6w plans to investigate a membrane complex that allows the malaria parasite to invade the red blood cells of a human host.<\/p>\n\n\n\n
\u201cThis membrane complex is fascinating,\u201d L\u00f6w explains. \u201cIt sits across multiple layers of the pathogen cell membrane and is very large. To visualise its atomic structure in high-resolution, we will use multiple techniques including crystallography and electron microscopy supported by Kay Gr\u00fcnewald of the Heinrich Pette Institute. The membrane complex is crucial for the survival of the malaria parasite, so a complete understanding of its structure and biology would enable us to design small molecules to block it, thereby halting the disease,\u201d says L\u00f6w.<\/p>\n\n\n\n
Even before groups moved into the building, interdisciplinary collaboration within the network developed during the CSSB\u2019s formation started bearing fruit. Thomas Marlovits, CSSB group leader from the University Hospital Hamburg Eppendorf, uses a range of structural biology methods to study groups of proteins called secretion systems that certain types of bacteria such as Salmonella<\/em> and E.coli<\/em> use to infect their host. Wilmanns teamed up with Marlovits to study a secretion system found in the tuberculosis pathogen Mycobacterium<\/em>. Using a combination of small-angle X-ray scattering and electron microscopy techniques complemented by biochemical and biophysical studies, the groups were able to reveal the unusual shape of the system and the unexpected position of the complex within the Mycobacterium<\/em> cell membrane. \u201cThe results advance our knowledge of how tuberculosis pathogens function,\u201d says Wilmanns. \u201cIt shows how powerful interdisciplinary studies can be for infection research.\u201d<\/p>\n\n\n\n CSSB is a joint initiative of ten research partners from northern Germany, including three universities and six research institutes.\n\n\n\n
The building will also host four core facilities using state-of-the-art technologies and equipment. Protein characterisation and crystallisation facilities at EMBL next door have been expanded and upgraded in order to serve both EMBL and CSSB. An advanced light and microscopy facility will be run in cooperation with leading microscope manufacturer Leica microsystems. A protein production facility is in the process of being set up. In addition, an in-house electron-microscopy facility will also be available, with four microscopes set to come online before the end of the year.<\/p>\n\n\n\n
![\"CSSB](\"https:\/\/news.embl.de\/wp-content\/uploads\/2017\/11\/Kosinski_EMBL_620x380-1.jpg\")
![\"\"](\"https:\/\/news.embl.de\/wp-content\/uploads\/2017\/10\/Curiosity_150x150.jpg\")
Curiosity is a profoundly human trait. We start asking questions almost as soon as we learn to speak and continuously redefine our understanding of the world by questioning it. This is the driving force behind science, technology, engineering and maths. As part of our curiosity editorial theme, we are exploring what EMBL is curious about.<\/p>\n