The Leukemia and Lymphoma Research has awarded a pilot-project grant to Dr Erika Mancini. The aim of the project is to try and estabish proof of principle for new structure-based, inhibitory molecule-mediated approaches to inhibit oncogenic protein-protein interactions in T-cell acute lymphoblastic leukemia. For more about Dr. Mancini's research, go to the Mancini Group's page.
David Bitto, a Strubi DPhil student in Dr. Juha Huiskonen's group and co-supervised by Dr. Kay Gruenewald, was awarded the 2012 Mary Goodger Scholarship. Goodger Scholarships are awarded to assist research into the causes and prevention of disease in its early stages. For more about Dr. Huiskonen's research, go to the Huiskonen Group's page.
Strubi is proud to announce that the Medical Research Council has awarded a three-year grant to Drs. Juha Huiskonen and Thomas Bowden to study the structure, entry and egress mechanism of severe hemorrhagic fever causing viruses. The aim of the project is to decipher molecular interactions that could be targeted by antiviral drugs. For more about Dr. Huiskonen's research, go to the Huiskonen Group's page.
Strubi is proud to announce that Dr. Christian Siebold has been awarded a Cancer Research UK Senior Cancer Research Fellowship to support his work on the molecular mechanisms of cell surface morphogen signalling. For more about Dr. Siebold's research, go to the Siebold Group's page.
Professor David Stuart, Director of the Division of Structural Biology and of the Instruct network, talks to the Times Higher Education Supplement about pan-European access to national cutting-edge biology facilities. Read more
The immune complement system in blood kills microbes by making ‘membrane-attack complex’ pores in cell membranes. This paper reveals the step-wise structural built-up of the pore and the host-cell protection from bystander damage. The data show how C6 captures C5b, which initiates the lytic process on cells recognized by complement. C7, C8αβγ and C9 dock sideways onto C6 aligning their barrel-forming domains in an arc. Vitronectin and clusterin enwrap the membrane perforating segments and block polymerization of C9. This intricate formation and regulation process provides mammals better control over this lethal weapon, than the related but simpler bacterial toxins. Read more
Work performed in the Stuart and Jones groups was highlighted in the recently released Hollywood film, ‘Contagion’. The recent emergence of the Nipah virus in South East Asia inspired the scientific background for the storyline. Our structure of the Nipah virus attachment glycoprotein, in complex with one of its functional entry receptors, ephrinB2, was included in the film to demonstrate the molecular basis for viral attachment and entry into its human target cell. The trailer for the film, which includes this structural data, can be seen here. Read more
Researchers in the Division of Structural Biology have used electron tomography to analyze the three-dimensional structure of HSV1 particles during anterograde axonal transport. Their data support the 'separate model' for HSV1 egress: that progeny herpes viruses are being transported along axons as subassemblies and not as complete virions within transport vesicles. Read more
Figure: Surface rendering of a tomogram showing secondary envelopment of capsids. Capsid (light blue), tegument (orange), glycoproteins (yellow), actin (red), plasma membrane and vesicle membrane (blue).
The human protein perforin is central to 'immune surveillance' whereby white blood cells patrol the body. These 'natural killer' cells use perforin to deliver a signal to virally infected and potentially cancerous cells, causing them to initiate a suicidal response. Researchers in the Division of Structural Biology studying perforin have discovered that in addition to forming pores in cell membranes, the protein can cause a unique form of 'endocytosis' (cell eating) whereby the suicidal signal is taken inside target cells without damaging the outer cell membrane. Read more
Figure: backgrond is a cryo-electron microscope image of a membrane being in-folded by perforin; foreground anticlockwise from top left live cell imaging of perforin's action on cells, a fluorescent microscope image of perforin's action on membranes, and an image of the perforin pore.
Strubi is proud to announce that Charlotte Coles, a freshly graduated DPhil student in the Division, has been awarded an NDM Graduate Prize for her doctoral work on the role of heparan and chondroitin sulfate proteoglycans in receptor protein tyrosine phosphatase sigma-mediated nerve regeneration. This resulted in a first author paper in Science. For more about this story, go to the NDM Prize Student profile page.
Radu Aricescu's and Yvonne Jones' groups have a new paper out in Science! Coles et al. report new results on the role of heparan and chondroitin sulfate proteoglycans in receptor protein tyrosine phosphatase sigma-mediated nerve regeneration. These results lead to a model where proteoglycans can exert opposing effects on neuronal extension by competing to control the oligomerization of a common receptor.
Coles et al. 2011. Proteoglycan-specific molecular switch for RPTPσ clustering and neuronal extension. Science, 332 (6028), pp. 484-488. 
Workshop on Mammalian Expression Technologies, Oxford, 3-8 April 2011, sponsored by P-CUBE. Organisers: Yvonne Jones, Radu Aricescu, Susan Daenke, Christian Siebold, Karl Harlos, Margaret Jones, Benjamin Bishop, Amber Clayton, Veronica Chang, Weixian lu, Tom Walter and Yuguang Zhao.
The course was designed primarily for structural biologists with prokaryotic expression experience who would like to use the mammalian expression system for more challenging targets. During the course, aside from lectures, all the participants had hands-on experience of mammalian cell culture, small and large scale transient gene expression and protein purification. Most of the participants brought their own plasmids for small scale expression, and all got their results by Western Blot analysis. Four participants brought their own constructs for large scale protein production, all of whom were able to purify their proteins with good yields. Three participants carried out crystallization screening with their purified proteins. One of the proteins crystallized immediately, and conditions were optimised to increase crystal size.
Students, postdocs and experienced scientists from 11 different countries (Germany, Denmark, Belgium, UK, France, Austria, Spain, Greece, Czech, Sweden, Switzerland) participated in the successful event and were happy to take advantage of the trans-national access offered by P-CUBE.
Juha Huiskonen in the Division has recently been awarded with a 4 year (2010-2014) Academy of Finland) research grant.
