BEGIN:VCALENDAR VERSION:2.0 PRODID:-//CERN//INDICO//EN BEGIN:VEVENT SUMMARY:Bismuth-NSAIDs as colorectal cancer chemopreventives DTSTART;VALUE=DATE-TIME:20181120T005000Z DTEND;VALUE=DATE-TIME:20181120T011000Z DTSTAMP;VALUE=DATE-TIME:20260510T120951Z UID:indico-contribution-632-2588@events01.synchrotron.org.au DESCRIPTION:Speakers: Tara Brown (University of Wolloongong)\nTo date\, ep idemiological studies\, animal studies and clinical trials have indicated the potential of non-steroidal anti-inflammatory drugs (NSAIDs) for the ch emoprevention of colorectal cancer (CRC) [1]. Unfortunately\, the use of N SAIDs for CRC chemoprevention is significantly limited due to the severe g astrointestinal (GI) side effects that have been associated with their lon g term use [1]. It is hypothesised that the coordination of NSAIDs to bism uth\, a heavy metal with proven gastrointestinal sparing properties [2]\, may allow the use of NSAIDs as chemopreventives for CRC while also combati ng their associated GI side effects. The present study investigates the in teractions of bismuth-coordinated NSAIDs (BiNSAIDs) with eukaryotic membra ne mimics with the aim of establishing the possible uptake mechanisms of t hese compounds. This knowledge will be extended by investigating the behav iour of BiNSAIDs in more complex systems\, including CRC cells and a CRC a nimal model.\n\nQCM-D studies involving biological membrane mimics compose d of POPC or POPC/cholesterol demonstrated that BiNSAIDs and their parent NSAIDs interact with biological membranes [3]. Neutron reflectometry was a lso used to study the membrane interactions of BiNSAIDs and provided furth er evidence of the membrane interactions of BiNSAIDs\, suggesting that pas sive diffusion is a likely method of uptake of these compounds [3]. These strength of these membrane interactions was an indicator of BiNSAID cytoto xicity against CRC cells.3 A CRC animal study has recently been completed with aspirin\, which has promising preliminary results. In conclusion\, th e aforementioned studies continue to highlight the potential of BiNSAIDs a s candidates for further investigations into their potential for the chemo prevention of CRC. \n\nReferences\n1. M. J. Thun\, S. J. Henley\, C. Patro no\, “Nonsteroidal Anti-inflammatory Drugs as Anticancer Agents: Mechani stic\, Pharmacologic\, and Clinical Issues”\, J. Natl. Cancer Inst.\, 94 \, 252-266 (2002)\n2. P. J. Sadler\, H. Li\, H. Sun\, “Coordination chem istry of metals in medicine: target sites for bismuth”\, Coord. Chem. Re v.\, 185-186\, 689-709 (1999)\n3. T. Brown\, “Bismuth-NSAIDs as colorect al cancer chemopreventives: Insights into their membrane interactions and uptake mechanisms”\, Bachelor of Medicinal Chemistry Advanced (Honours) Dissertation\, University of Wollongong\, (2016)\n\nhttps://events01.synch rotron.org.au/event/84/contributions/2588/ LOCATION:AINSE Conference Centre New Illawarra Road Lucas Heights NSW 2234 Australia URL:https://events01.synchrotron.org.au/event/84/contributions/2588/ END:VEVENT BEGIN:VEVENT SUMMARY:HIERARCHICAL ARCHITECTURE OF CELLULOSE AND ITS INTERACTION WITH OT HER PLANT CELL WALL POLYSACCHARIDES DTSTART;VALUE=DATE-TIME:20181120T011000Z DTEND;VALUE=DATE-TIME:20181120T013000Z DTSTAMP;VALUE=DATE-TIME:20260510T120951Z UID:indico-contribution-632-2347@events01.synchrotron.org.au DESCRIPTION:Speakers: Elliot Gilbert (ANSTO)\nPlant cell walls (PCWs) are extremely complex structures in which cellulose microfibrils are hierarchi cally assembled and embedded in a multi-component matrix. While the cellul ose microfibrils represent the basic building unit providing mechanical st rength [1]\, the matrix components are able to tune the properties of each specific tissue [2-3]\, increasing the flexibility or limiting the transp ort of moisture\, for instance.\n\nThe synthesis of cellulose hydrogels by means of bacterial fermentation is an efficient approach to mimic the cel l wall biosynthesis process and investigate the interactions established b etween cellulose and matrix polysaccharides by incorporating the latter in to the culture medium. We have characterised cellulose hydrogels and their composites with PCW polysaccharides by means of SANS and SAXS\, combined with complementary techniques such as X-ray diffraction\, spectroscopy and microscopy. Furthermore\, the production of partially deuterated cellulos e hydrogels by using a deuterated glucose-based feedstock is presented as a strategy to enhance the neutron scattering length density contrast [4].\ n\nThe application of a multi-technique characterisation approach enabled elucidation of the complex hierarchical architecture of cellulose hydrogel s and led to the development of a multi-scale model based on core-shell st ructures [4-8]. The model describes the multi-phase structure of cellulose microfibrils and ribbons\, as well as the essential role of water at the different structural levels. In addition\, USANS experiments are presented as a promising method to characterise the structure of native cellulose i n the longitudinal direction\, providing information on the microfibril le ngth and ribbon twisting periodicity.\n\nPCW polysaccharides such as xylog lucan\, arabinoxylan\, mixed linkage glucans and pectins during cellulose synthesis have a distinct structural role and interaction mechanism with c ellulose (interfering with the crystallisation process and strongly intera cting with the cellulose microfibrils\, or establishing interactions at th e ribbons’ surface level).\n\nThese results highlight the ability of sma ll angle scattering techniques to provide valuable insights on cellulose b iosynthesis and interactions with PCW polysaccharides.\n\nhttps://events01 .synchrotron.org.au/event/84/contributions/2347/ LOCATION:AINSE Conference Centre New Illawarra Road Lucas Heights NSW 2234 Australia URL:https://events01.synchrotron.org.au/event/84/contributions/2347/ END:VEVENT BEGIN:VEVENT SUMMARY:Using neutrons to elucidate the molecular details of enzyme isofor m selectivity by small molecule inhibitors. DTSTART;VALUE=DATE-TIME:20181120T000000Z DTEND;VALUE=DATE-TIME:20181120T003000Z DTSTAMP;VALUE=DATE-TIME:20260510T120951Z UID:indico-contribution-632-2293@events01.synchrotron.org.au DESCRIPTION:Speakers: Zoë Fisher (European Spallation Source ERIC)\nHuman carbonic anhydrase IX (CA IX) expression is activated by hypoxic conditio n in aggressive\, metastatic tumors. Cancer patietns positive for CA IX ha ve generally a poor prognosis. CA IX has emerged as an important cancer ta rget\, but efforts to develop isoform selective inhibitors are complicated by the presence of 14 other CA isoforms that share high sequence and stru ctural similarity. This leads to off-target inhibitor binding and side eff ects. Recent studies showed that saccharin (SAC) already shows some isofor m discrimination\, and that conjugating SAC to a glucose molecule (Sacchar in-Glucose Conjugate\, SGC) further improves the Ki against CA IX by 2-fol d. \nLigand binding to proteins are mediated through numerous interactions \, including: H-bonding directly and/or through intervening waters\, elect rostatic interactions with charged or polar amino acid side chains\, metal coordination\, energetic changes through water displacement\, aromatic ri ng stacking\, or other hydrophobic interactions. As neutrons scatter stron gly from atomic nuclei of light atoms 1H (Hydrogen)\, and its isotope 2H ( Deuterium)\, it is possible to use neutron protein crystallography (NPX) t o “see” the light atoms and any interactions they are involved with. ( e.g. H-bonds). \nWe used joint X-ray and neutron crystallography methods t o determine the crystal structures of a CA IX mimic alone and in complex w ith SAC and SGC\, respectively. Our analyses reveal the molecular details of solvent displacement upon ligand binding\, the H-bonding between the li gands and the proteins\, involvement of water-mediated H-bonds\, and the r emodeling of H-bonds to accommodate ligand binding. The structures and ana lysis also provide an explanation for the observed CA isoform selectivity of the ligand under study.\n\nhttps://events01.synchrotron.org.au/event/84 /contributions/2293/ LOCATION:AINSE Conference Centre New Illawarra Road Lucas Heights NSW 2234 Australia URL:https://events01.synchrotron.org.au/event/84/contributions/2293/ END:VEVENT BEGIN:VEVENT SUMMARY:Understanding the interaction between the Proteus mirabilis Scs pr oteins using neutron scattering DTSTART;VALUE=DATE-TIME:20181120T003000Z DTEND;VALUE=DATE-TIME:20181120T005000Z DTSTAMP;VALUE=DATE-TIME:20260510T120951Z UID:indico-contribution-632-2348@events01.synchrotron.org.au DESCRIPTION:Speakers: Andrew Whitten (ANSTO)\nCorrectly forming disulphide bonds is critical to the folding of a wide variety of proteins. Bacterial virulence factors are one class of proteins containing disulfide bonds\, thus\, an approach to disarm virulent bacterial might involve shutting dow n the machinery involved in the formation of disulfide bonds. The suppress or of copper sensitivity (Scs) proteins form part of the disulfide bond fo rming machinery in bacteria\, and it is hoped that determining the structu re of molecules such as this may lead to the development of new classes of antibiotics. There are four Scs proteins (ScsA\, B\, C and D) present in numerous Gram-negative bacteria\, and few have been structurally character ised. In this work\, we have created cysteine variants of PmScsC and PmScs B to produce a stable complex and using small-angle X-ray and neutron scat tering with contrast variation\, we have determined the low-resolution str ucture of the PmScsC–PmScsB complex.\n\nhttps://events01.synchrotron.org .au/event/84/contributions/2348/ LOCATION:AINSE Conference Centre New Illawarra Road Lucas Heights NSW 2234 Australia URL:https://events01.synchrotron.org.au/event/84/contributions/2348/ END:VEVENT END:VCALENDAR