BEGIN:VCALENDAR VERSION:2.0 PRODID:-//CERN//INDICO//EN BEGIN:VEVENT SUMMARY:Short Talk 5\, Ronnie Berntsson - Structural insight into Gram-pos itive Type 4 Secretion Systems DTSTART;VALUE=DATE-TIME:20191010T074000Z DTEND;VALUE=DATE-TIME:20191010T080000Z DTSTAMP;VALUE=DATE-TIME:20260526T135934Z UID:indico-contribution-137-761@lindico453.srv.lu.se DESCRIPTION:Speakers: Ronnie Berntsson (Umeå University)\nMultidrug resis tance in bacteria\, originating from conjugative gene transfer\, is an inc reasingly common problem\nin today’s world. The majority of bacteria tha t causes hospital infections are of gram-positive origin\,\nbut so far ver y little is known about their conjugation systems. To remedy this\, we aim to determine the\nmolecular structure and function of conjugation complex es belonging to Type IV Secretion Systems (T4SSs)\nfrom gram-positive bact eria. This will lead to a deeper insight into one of the main processes re sponsible for\nhorizontal gene transfer events\, including the spread of a ntibiotic resistance genes in bacteria.\nWe study the proteins involved in forming the T4SS biochemically\, structurally and biophysically. Since gr ampositive\nT4SSs are very dissimilar from their gram-negative counterpart s\, little can be deduced from the few\ngram-negative systems so far studi ed. Furthermore\, they occur in a number of pathogens\, such as enterococc i\,\nstreptococci and staphylococci. Another aspect that makes gram-positi ve T4SSs interesting is that they are\nused to efficiently transfer not on ly antibiotic resistance\, but also virulence factors.\nThese megadalton s ized systems are built up by i) extracellular adhesion proteins\, ii) memb rane channel proteins\nand iii) intracellular DNA processing proteins. Her e\, I will present our current understanding of the\nT4SS originating from the conjugative plasmid pCF10 of Enterococcus faecalis. Our work on this system\ncombines molecular biology\, biochemistry\, X-ray crystallography and Electron Microscopy. This has so far\nallowed us to determine structur es and understand some of the functions of the adhesion proteins as well a s\npart of the DNA processing proteins\, which will highlight both major d ifferences and similarities between the\ngram-positive and gram-negative s ystems.\n\nhttps://lindico453.srv.lu.se/event/125/contributions/761/ LOCATION:Kulturen Auditorium URL:https://lindico453.srv.lu.se/event/125/contributions/761/ END:VEVENT BEGIN:VEVENT SUMMARY:Keynote 4\, Prof. Yvonne Jones: From structure to mechanism in the assembly and modulation of cell surface signalling complexes. DTSTART;VALUE=DATE-TIME:20191010T070000Z DTEND;VALUE=DATE-TIME:20191010T074000Z DTSTAMP;VALUE=DATE-TIME:20260526T135934Z UID:indico-contribution-137-760@lindico453.srv.lu.se DESCRIPTION:Speakers: Yvonne Jones (Univ. of Oxford\, UK)\nIn my laborato ry we combine crystallographic\, biophysical\, electron and light microsco py based approaches into integrated structural biology analyses to study t he assembly and modulation of cell surface signalling complexes involved i n development and tissue homeostasis. We aim to generate mechanistic insig hts\, at atomic resolution\, which can be tested by functional studies in vitro and in vivo. I will discuss some of the recent results we have gener ated by applying this approach to the signalling mechanism of the semaphor in-plexin cell guidance system and to the extracellular modulation of sign alling by the morphogen Wnt. Published examples of our work on these two s ystems include the following:\n\nD. Rozbesky*\, R.A. Robinson\, V. Jain\, M. Renner\, T. Malinauskas\, K. Harlos\, C. Siebold\, and E.Y. Jones*. (20 19) Diversity of oligomerization in Drosophila semaphorins suggests a mech anism of functional fine-tuning. Nature Commun. 10\, 3691.\n\nY. Kong=\, B .J.C. Janssen=\, T. Malinauskas\, V.R. Vangoor\, C.H. Coles\, R. Kaufmann\ , T. Ni\, R.J.C. Gilbert\, S. Padilla-Parra\, R.J. Pasterkamp* and E.Y. Jo nes* (2016) ‘Structural basis for plexin activation and regulation.’ N euron 91\, 548-560\n\nS. Kakugawa=\, P.F. Langton=\, M. Zebisch=*\, S. How ell\, T.-H. Chang\, Y. Liu\, T. Feizi\, G. Bineva\, N. O'Reilly\, A.P. Sni jders\, E.Y. Jones* and J.-P. Vincent*. (2015) ‘Notum deacylates Wnts to suppress signalling activity.’ Nature 519\, 187-192\n\nhttps://lindico4 53.srv.lu.se/event/125/contributions/760/ LOCATION:Kulturen Auditorium URL:https://lindico453.srv.lu.se/event/125/contributions/760/ END:VEVENT BEGIN:VEVENT SUMMARY:Keynote 5\, Prof Liz Carpenter: Using Structural biology of human membrane proteins to understand the causes of genetic diseases DTSTART;VALUE=DATE-TIME:20191010T080000Z DTEND;VALUE=DATE-TIME:20191010T084000Z DTSTAMP;VALUE=DATE-TIME:20260526T135934Z UID:indico-contribution-137-762@lindico453.srv.lu.se DESCRIPTION:Speakers: Liz Carpenter (University of Oxford\, UK)\nThe human genome project and subsequent sequencing efforts of thousands of patients and healthy individual provides a wealth of associations between variants in genes and diseases. At the SGC our aim is to create a step-change in d rug development by providing tools (proteins\, structures\, assays and bou nd small molecules)\, for proteins that are have associations with genetic disease. We focus in particular on proteins that are associated with neur opsychiatry\, cancer\, rare and metabolic disease\, as well as inflammator y conditions. These “Target Enabling Packages” or TEPs\, are made free ly available to advance our understanding of the biology of disease and to assist in the design of therapeutics. The Carpenter group focuses on inte gral membrane proteins\, including ion channels\, solute carriers\, ABC tr ansporters and enzymes. Here\, I will discuss three examples of genetic hi ts\, PKD2 in kidney disease\, TMEM16K in ataxia and DPAGT1 in congenital m yasthenia\, for which we have obtained structures\, and a wealth of additi onal improvement in our understanding disease biology. These examples of s tructures of genetic hits illustrate the power of structural biology\, as well as the need for extensive additional information\, to provide an unde rstanding of disease biology\, which is essential for development of thera peutics.\n\nhttps://lindico453.srv.lu.se/event/125/contributions/762/ LOCATION:Kulturen Auditorium URL:https://lindico453.srv.lu.se/event/125/contributions/762/ END:VEVENT END:VCALENDAR