Gordon Research Conferences
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Conference Program
 
Multi-Drug Efflux Systems
From Molecular Mechanisms to Pharmacological Modulation
June 12-17, 2011
Les Diablerets Conference Center
Les Diablerets, Switzerland

All living cells use special membrane transport proteins to keep their interiors free from toxic products of cellular metabolism and a variety of environmental toxins. A single multi-drug resistance (MDR) transporter might handle literally hundreds of structurally diverse compounds. This substrate promiscuity makes MDR transporters a fascinating subject of research. By the same token, however, it renders some of them a serious impediment to human healthcare, since many of their substrates are clinically useful drugs used to fight cancer and various infections caused by fungi, parasites and bacteria. Three previous Gordon Research Conferences on Multi-Drug Efflux Systems firmly established this series of meetings as an open and stimulating forum for scientific exchange in all basic and applied aspects of polyspecific membrane efflux transporters. By bringing together investigators pursuing studies of distinct but evolutionary and mechanistically overlapping efflux systems, the conference facilitates cross-fertilizing ideas and insights in the field which is crucial for our ability to successfully combat both cancer cells and microbial pathogens. Since its inception the conference reinforced its international aspect by alternating between US and European venues. The 4th meeting on Multi-Drug Efflux Systems will be held in the heart of the beautiful Swiss Alps.

The 2011 meeting will focus on recent advances in unraveling molecular mechanisms of transport and multi-drug recognition based on biochemical, genetic and structural studies. Special emphasis will be made on new methods and techniques to study membrane proteins. Many other aspects such as the cellular mechanisms regulating activity of MDR transporters, the physiological functions of MDR transporters in various organisms and their pathophysiological functions in humans will be also covered by leading scientists and representatives of pharmaceutical companies from all over the world. Various strategies of pharmacological modulation of function of MDR transporters to improve the clinical outcomes of chemotherapy will be discussed at large. It is expected that the broad range of topics combined with intense informal scientific interactions in the pleasant setting at Les Diablerets will result in many new ideas and approaches.


Contributors

SUNDAY
4:00 pm - 8:00 pmArrival and Check-in (Check-in Desk Closed 6:00 pm - 7:45 pm)
6:00 pmDinner
7:30 pm - 7:35 pmWelcome / Introductory Comments by GRC Site Staff
7:35 pm - 7:40 pmOlga Lomovskaya & Anthony George, Co-Chairs for Conference
Introductory Comments & Conference Welcome
7:40 pm - 9:30 pmKeynote Session
7:40 pm - 7:50 pmDiscussion Leader: Shimon Schuldiner (Hebrew University, Jerusalem, Israel)
7:50 pm - 8:30 pmPiet Borst (University of Amsterdam, Amsterdam, Netherlands)
"Drug efflux transporters and their role in cancer cell resistance and survival"
8:30 pm - 8:40 pmDiscussion
8:40 pm - 9:20 pmHiroshi Nikaido (University of California, Berkeley, USA)
"Capture and transport of diverse substrates by transmembrane and cismembrane MDR pumps"
9:20 pm - 9:30 pmDiscussion
MONDAY
7:30 am - 8:30 amBreakfast
9:00 am - 12:30 pmSignificance of Efflux in Multi-Drug Resistance
9:00 am - 9:10 amDiscussion Leader: J.V. Piddock (University of Birmingham, UK)
9:10 am - 9:30 amPatrice Courvalin (Institute Pasteur, Paris, France)
"Efflux and Antibiotic Resistance in Acinetobacter"
9:30 am - 9:40 amDiscussion
9:40 am - 10:00 amDominique Sanglard (Vaudois University, Lausanne, Switzerland)
"Participation of ABC transporters in drug resistance and virulence in the human pathogen Candida glabrata"
10:00 am - 10:10 amDiscussion
10:10 am - 10:40 amCoffee Break
10:40 am - 11:00 amPatrick Plesiat (Hôpital Jean Minjoz, Besancon Cedex, France)
"Active efflux as part of the stress response in Gram negative bacteria"
11:00 am - 11:10 amDiscussion
11:10 am - 11:30 amSusan Bates (National Cancer Institute, Bethesda, USA)
"Efflux Transporters and Drug Penetration: An Unproven Link" [Lecture in Honor of Dr. Gary Kruh]
11:30 am - 11:40 amDiscussion
11:40 am - 12:00 pmFrancoise van Bambeke (Catholic University of Louvain, Brussels, Belgium)
"How do antibiotics play with efflux transporters in mammalian and bacterial cells?"
12:00 pm - 12:10 pmDiscussion
12:10 pm - 12:25 pmFrederica Theodoulou (Rothamsted Research, Harpenden, UK)
"ABC transporters in plants: multiple, broad or narrow substrate specificity?"
12:25 pm - 12:30 pmDiscussion
12:30 pmGroup Photo / Lunch
1:30 pm - 4:00 pmFree Time
4:00 pm - 5:30 pmPoster Session
5:30 pm - 7:30 pmDiversity of Biological Functions
Discussion Leader: Attilio Di Pietro (CNRS Lyon, France)
5:30 pm - 5:50 pmMichelle Haber (Children's Cancer Institute for Medical Research, Australia)
"Multidrug transporters as potential oncogenes"
5:50 pm - 6:00 pmDiscussion
6:00 pm - 6:20 pmRobert Tampe (Frankfurt University, Germany)
"Mechanism of ABC transporters in immunity"
6:20 pm - 6:30 pmDiscussion
6:30 pm - 6:50 pmDavid Fidock (Columbia University, New York, USA)
"Recent insights into antimalarial resistance mediated by Plasmodium falciparum multidrug efflux pumps"
6:50 pm - 7:00 pmDiscussion
7:00 pm - 7:20 pmJesús Blázquez (National Center for Biotechnology, Spanish Research Council - CSIC)
"Role of MATE efflux pumps on oxidative damage protection and antimutation"
7:20 pm - 7:30 pmDiscussion
8:00 pmDinner
TUESDAY
7:30 am - 8:30 amBreakfast
9:00 am - 12:30 pmStructure and Mechanism of Multi-Drug Efflux Pumps 1
9:00 am - 9:10 amDiscussion Leader: Robert Ford (University of Manchester, UK)
9:10 am - 9:30 amMarkus Gruetter (University of Zurich, Zurich, Switzerland)
"Structure and mechanism of heterodimeric ABC transporters"
9:30 am - 9:40 amDiscussion
9:40 am - 10:00 amSuresh Ambudkar (National Cancer Institute, Bethasda, USA)
"The mechanism of action of P-glycoprotein (ABCB1)"
10:00 am - 10:10 am Discussion
10:10 am - 10:40 amCoffee Break
10:40 am - 11:00 amFrances Sharom (University of Guelph, Ontario, Canada)
"Probing the drug-binding pocket and drug transport mechanism of P-glycoprotein (ABCB1)"
11:00 am - 11:10 amDiscussion
11:10 am - 11:30 amRichard Callaghan (University of Oxford, Oxford, UK)
"Molecular mechanisms associated with multidrug resistance mediators"
11:30 am - 11:40 amDiscussion
11:40 am - 12:00 pmLutz Schmitt (Heinrich Heine University Duesseldorf, Germany)
"X-ray meets flexible membrane transporters - pitfalls, challenges and insights"
12:00 pm - 12:10 pmDiscussion
12:10 pm - 12:25 pmAlice Rothnie (Aston Triangle, Birmingham, UK)
"Detergent free purification of ABC transporters using SMA polymer"
12:25 pm - 12:30 pmDiscussion
12:30 pmLunch
1:30 pm - 4:00 pmFree Time
4:00 pm - 5:30 pmPoster Session
5:30 pm - 7:30 pmNew Methods to Study Membrane Transporters
Discussion Leader: Helen Zgurskaya (Oklahoma University, Norman, USA)
5:30 pm - 5:50 pmFraser MacMillan (University of East Anglia, Norwich, UK)
"Watching membrane proteins move using EPR spectroscopy"
5:50 pm - 6:00 pmDiscussion
6:00 pm - 6:20 pmAnna Seelig (University of Basel, Switzerland)
"New methods to monitor P-glycoprotein activity: Microphysiometry and NMR in living cells"
6:20 pm - 6:30 pmDiscussion
6:30 pm - 6:50 pmArnaud Ducruix (Paris Descartes University, Paris, France)
"Structural and Dynamical Insights into the Opening and assembly Mechanism of P. aeruginosa efflux pumps"
6:50 pm - 7:00 pmDiscussion
7:00 pm - 7:20 pmXiao-Hong Nancy Xu (Old Dominion University, Norfolk, USA)
"Nanoassay for Real-Time Molecular Probing of Multidrug Membrane Transporters"
7:20 pm - 7:30 pmDiscussion
8:00 pmDinner
WEDNESDAY
7:30 am - 8:30 amBreakfast
9:00 am - 12:30 pmStructure and Mechanism of Multi-Drug Efflux Pumps 2
9:00 am - 9:10 amDiscussion Leader: Martin Pos (University of Frankfurt, Germany)
9:10 am - 9:30 amHendrik van Veen (University of Cambridge, UK)
"Mechanisms of drug and ion transport by the MFS multidrug transporter LmrP"
9:30 am - 9:40 amDiscussion
9:40 am - 10:00 amEitan Bibi (Weizmann Institute of Science, Rehovot, Israel)
"Molecular aspects of secondary multidrug transport"
10:00 am - 10:10 amDiscussion
10:10 am - 10:40 amCoffee Break
10:40 am - 11:00 amHassane S. Mchaourab (Vanderbilt University, Nashville, USA)
"Structural Dynamics of Multi-Drug Transporters"
11:00 am - 11:10 amDiscussion
11:10 am - 11:30 amPaolo Ruggerone (University of Cagliari, Italy)
"Molecular modeling of antibiotic translocation coupled to functional rotation in AcrB"
11:30 am - 11:40 amDiscussion
11:40 am - 12:00 pmEdward Yu (Iowa State University, Iowa, USA)
"Crystal structures of the CusA efflux pump"
12:00 pm - 12:10 pmDiscussion
12:10 pm - 12:25 pmUte Andrea Hellmich (Goethe University Frankfurt, Germany)
"Extensive conformational changes throughout the ATP hydrolysis cycle of the ABC multidrug transporter LmrA"
12:25 pm - 12:30 pmDiscussion
12:30 pmLunch
1:30 pm - 4:00 pmFree Time
4:00 pm - 5:30 pmPoster Session
5:30 pm - 7:30 pmControl of Gene Expression / Modulation of Activity
Discussion Leader: Karl Kuchler (Medical University Vienna, Austria)
5:30 pm - 5:50 pmWilliam Shafer (Emory University School of Medicine, Georgia, USA)
"Genetic control of drug efflux pump gene expression in Neisseria gonorrhoeae: implications for pathogenesis"
5:50 pm - 6:00 pmDiscussion
6:00 pm - 6:20 pmScott Moye-Rowley (University of Iowa, Iowa City, USA)
"Regulation of Multidrug Resistance in Fungi"
6:20 pm - 6:30 pmDiscussion
6:30 pm - 6:50 pmGert Fricker (University of Heidelberg, Heidelberg, Germany)
"Regulation of ABC drug transporters by nuclear receptors"
6:50 pm - 7:00 pmDiscussion
7:00 pm - 7:20 pmToshihisa Ishikawa (RIKEN, Yokohama, Japan)
"Pharmacogenomics of human ABC transporters"
7:20 pm - 7:30 pmDiscussion
7:30 pm - 8:00 pmBusiness Meeting
Nominations for the next Vice Chair; Fill out Conference Evaluation Forms; Discuss future Site & Scheduling preferences; Election of the next Vice Chair
8:00 pmDinner
THURSDAY
7:30 am - 8:30 amBreakfast
9:00 am - 12:30 pmApproaches to Overcome/Modulate Multiple Drug Resistance
9:00 am - 9:10 amDiscussion Leader: Susan Bates (National Cancer Institute, Bethesda, USA)
9:10 am - 9:30 amZhe-Sheng (Jason) Chen (St. John's University, New York, USA)
"PDE5 inhibitors as modulators of ABC transporter mediated multidrug resistance in cancer"
9:30 am - 9:40 amDiscussion
9:40 am - 10:00 amHeidrun Potschka (Ludwig Maximilian University, Munich, Germany)
"Targeting regulation of P-glycoprotein: a novel approach to overcome drug resistance"
10:00 am - 10:10 amDiscussion
10:10 am - 10:40 amCoffee Break
10:40 am - 11:00 amGergely Szakacs (Institute of Enzymology, Budapest, Hungary)
"Exploiting the paradoxical hypersensitivity of MDR cells: hitting cancer's Achilles' heel"
11:00 am - 11:10 amDiscussion
11:10 am - 11:30 amCharles Thompson (University of British Columbia, Vancouver, Canada)
"Chemical inactivation of drug efflux systems to increase the activities of clinically proven antibiotics against Mycobacterium tuberculosis"
11:30 am - 11:40 amDiscussion
11:40 am - 12:00 pmJean-Michel Bolla (School of Medicine, Marseille, France)
"Competitive- and noncompetitive inhibition of efflux pumps: from a natural source to the synthesis of new compounds"
12:00 pm - 12:10 pmDiscussion
12:10 pm - 12:25 pmShort Talk (TBA)
12:25 pm - 12:30 pmDiscussion
12:30 pmLunch
1:30 pm - 4:00 pmFree Time
4:00 pm - 5:30 pmPoster Session
5:30 pm - 7:30 pmPolyspecific Transporters in Drug Discovery, Development and Response
Discussion Leader: Wright Nichols (AstraZeneca, Waltham, USA)
5:30 pm - 5:50 pmCharles Dean (Novartis, Cambridge, USA)
"Efflux and Gram negative antimicrobial drug discovery: always the twain shall meet"
5:50 pm - 6:00 pmDiscussion
6:00 pm - 6:20 pmMark Warren (Optivia Biotechnology, Menlo Park, USA)
"Transporting Drug Development Past Roadblocks on the Critical Path"
6:20 pm - 6:30 pmDiscussion
6:30 pm - 6:50 pmJoseph Polli (GSK, USA)
"What's all the flux about? Case studies of the importance of drug transporters in drug discovery and development"
6:50 pm - 7:00 pmDiscussion
7:00 pm - 7:20 pmWilliam Guggino (John Hopkins University, Baltimore, USA)
"Processing mutations in ABCG2, newly recognized as a urate efflux pump, are associated with high plasma urate and gout"
7:20 pm - 7:30 pmDiscussion
8:00 pmDinner
FRIDAY
7:30 am - 8:30 amBreakfast
9:00 amDeparture

Funding for this conference was made possible (in part) by R13 GM099085-01 from the National Institute of Mental Health. The views expressed in written conference materials or publications and by speakers and moderators do not necessarily reflect the official policies of the Department of Health and Human Services; nor does mention by trade names, commercial practices, or organizations imply endorsement by the U.S. Government.

 
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