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DNA Topoisomerases in Biology & Medicine
Gordon Research Conference

The Interplay of DNA Topoisomerases and DNA Topology in Biology - Emerging Technologies, Dynamics of Enzyme Function and Opportunities in Drug Discovery

Dates

August 7-12, 2016

Location

Grand Summit Hotel at Sunday River
Newry, ME

Organizers

Chair:
Mary-Ann Bjornsti

Vice Chair:
Yves G. Pommier

Meeting Description

The 2016 DNA Topoisomerases in Biology and Medicine Gordon Research Conference and Associated Gordon Research Seminar provides a forum for the presentation and discussion of recent scientific and methodological advances in the study of DNA topoisomerases and the development of therapeutics that target these enzymes. The meeting will attract scientists in academia and industry from a broad range of disciplines, including structural biology, mechanistic enzymology, biophysics, genetics, pharmacology, drug discovery, cell biology and medicine, with a fertile mix of ideas and approaches. The associated GRS provides an opportunity for graduate students, post-docs, and other early-stage investigators to come together to discuss their current research and build informal networks with their peers. The primary focus of the GRC meeting is to attract scientists with a broad range of backgrounds with the consequent exposure of delegates to different approaches and techniques. The first theme of the meeting will focus on technological innovations that allow the complex interplay of DNA topoisomerases and DNA topology to be tackled, including advances in nano-manipulation of enzyme-DNA complexes and molecular dynamics simulations. A second theme will focus on recent advances in the structural determinations of topoisomerases and exciting new insights gained into the molecular mechanisms of enzyme function. A third theme is on the development of novel microbial and cancer therapeutics that target topoisomerases, and how advances in imaging technologies and proteomics/genomics are enabling new insights into the cellular roles of topoisomerases and their significance in human cancers. The study of these enzymes in the context of cellular processes is of critical importance in research leading to the development of new chemotherapeutic agents. Collectively we aim to showcase new approaches and encourage the cross-fertilization of disciplines that will stimulate new perspectives and new thinking about the roles of topoisomerases in biology and medicine.

Related Meeting

This GRC was held in conjunction with the "DNA Topoisomerases in Biology & Medicine" Gordon Research Seminar (GRS). Refer to the associated GRS program page for more information.

Contributors

Final Meeting Program

Sunday
2:00 pm - 9:00 pmArrival and Check-in
6:00 pmDinner
7:30 pm - 7:40 pmWelcome / Introductory Comments by GRC Site Staff
7:40 pm - 9:30 pmKeynote Session: The Biological Impact of DNA Topology: What Have We Learned?
Discussion Leader: Stewart Shuman (Memorial Sloan Kettering Cancer Center, USA)
7:40 pm - 7:50 pmIntroduction by Discussion Leader
7:50 pm - 8:25 pmKarl Drlica (Rutgers University, USA)
"Quinolone-Mediated Cell Death"
8:25 pm - 8:40 pmDiscussion
8:40 pm - 9:15 pmJames Berger (Johns Hopkins University, USA)
"Structural and Biochemical Investigations of Type II Topoisomerases"
9:15 pm - 9:30 pmDiscussion
Monday
7:30 am - 8:30 amBreakfast
9:00 am - 12:30 pmDNA Topology and Biological Processes
Discussion Leader: Lynn Zechiedrich (Baylor College of Medicine, USA)
9:00 am - 9:10 amIntroduction by Discussion Leader
9:10 am - 9:40 amAndrzej Stasiak (University of Lausanne, Switzerland)
"DNA Topology and Chromosome Organization"
9:40 am - 9:55 amDiscussion
9:55 am - 10:25 amCoffee Break
10:25 am - 10:55 amJoaquim Roca (Molecular Biology Institute of Barcelona, CSIC, Spain)
"Chromosomal DNA Topology: Topoisomerases Handle Extremely Supercoiled, Catenated and Knotted Chromatin Conformations"
10:55 am - 11:10 amDiscussion
11:10 am - 11:40 amMichelle Wang (Cornell University, USA)
"DNA Supercoiling and Its Regulation of Transcription"
11:40 am - 11:55 amDiscussion
11:55 am - 12:05 pmSelected from Poster Abstracts: Jonathan Fogg (Baylor College of Medicine, USA)
"Structural Diversity of Supercoiled DNA"
12:05 pm - 12:10 pmDiscussion
12:10 pm - 12:20 pmSelected from Poster Abstracts: Kevin Lang (University of Washington, USA)
"Topological Barriers at Replication-Transcription Conflicts"
12:20 pm - 12:25 pmDiscussion
12:25 pm - 12:30 pmGeneral Discussion
12:30 pmLunch
1:30 pm - 4:00 pmFree Time
4:00 pm - 6:00 pmPoster Session
6:00 pmDinner
7:30 pm - 9:30 pmSingle Molecule Analyses of DNA Topoisomerizations
Discussion Leader: Dagmar Klostermeier (University of Münster, Germany)
7:30 pm - 7:40 pmIntroduction by Discussion Leader
7:40 pm - 8:10 pmStephen Kowalczykowski (University of California, Davis, USA)
"Functions of Topoisomerases and Motor Proteins in DNA Branch Migration"
8:10 pm - 8:25 pmDiscussion
8:25 pm - 8:55 pmJohn Marko (Northwestern University, USA)
"Biophysical Studies of DNA Compaction and Topology Control: From Single Molecules to Chromosomes and Nuclei"
8:55 pm - 9:10 pmDiscussion
9:10 pm - 9:20 pmSelected from Poster Abstracts: Kathryn Gunn (Northwestern University, USA)
"Concurrent MT-TIRF Studies of Type IA Topoisomerases"
9:20 pm - 9:25 pmDiscussion
9:25 pm - 9:30 pmGeneral Discussion
Tuesday
7:30 am - 8:30 amBreakfast
9:00 am - 12:30 pmBacterial Topoisomerases as Drug Targets: Opportunities and Challenges
Discussion Leader: Yuk-Ching Tse-Dinh (Florida International University, USA)
9:00 am - 9:10 amIntroduction by Discussion Leader
9:10 am - 9:40 amCharles Dorman (Trinity College Dublin, Ireland)
"DNA Topology and Bacterial Species Determination"
9:40 am - 9:55 amDiscussion
9:55 am - 10:25 amCoffee Break
10:25 am - 10:55 amAnthony Maxwell (John Innes Centre, United Kingdom)
"New Ways to Target DNA Gyrase: A Well-Validated Target for Antibacterial Chemotherapy"
10:55 am - 11:10 amDiscussion
11:10 am - 11:40 amDavid Hooper (Massachusetts General Hospital, USA)
"Plasmid-Mediated Resistance to Topoisomerase-Targeting Agents"
11:40 am - 11:55 amDiscussion
11:55 am - 12:05 pmSelected from Poster Abstracts: Thomas Germe (John Innes Centre, United Kingdom)
"New Allosteric Inhibitors of DNA Gyrase Reveal a Stepwise Re-Ligation Mechanism"
12:05 pm - 12:10 pmDiscussion
12:10 pm - 12:20 pmSelected from Poster Abstracts: Valakunja Nagaraja (Indian Institute of Science, India)
"Targeting Topology Modulator HU and Topoisomerase I of Mycobacterium tuberculosis with Small Molecule Inhibitors"
12:20 pm - 12:25 pmDiscussion
12:25 pm - 12:30 pmGeneral Discussion
12:30 pmLunch
1:30 pm - 4:00 pmFree Time
4:00 pm - 6:00 pmPoster Session
6:00 pmDinner
7:30 pm - 9:30 pmTopoisomerases: Structure, Protein Interactions and Enzyme Mechanism
Discussion Leader: Keir Neuman (National Institutes of Health, USA)
7:30 pm - 7:40 pmIntroduction by Discussion Leader
7:40 pm - 8:10 pmRam Madabhushi (Massachusetts Institute of Technology, USA)
"Upon Stimulation, Neurons Take Breaks"
8:10 pm - 8:25 pmDiscussion
8:25 pm - 8:55 pmClaudine Mayer (Institut Pasteur, France)
"Structural Insights into Unusual Type II Topoisomerases"
8:55 pm - 9:10 pmDiscussion
9:10 pm - 9:20 pmSelected from Poster Abstracts: Valerie Lamour (Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), France)
"Improvement of the 3D Model of DNA Gyrase from Cryo-Electron Microscopy Data"
9:20 pm - 9:25 pmDiscussion
9:25 pm - 9:30 pmGeneral Discussion
Wednesday
7:30 am - 8:30 amBreakfast
8:30 amGroup Photo
9:00 am - 12:30 pmTopoisomerases and Genomic Stability
Discussion Leader: John Nitiss (University of Illinois, USA)
9:00 am - 9:10 amIntroduction by Discussion Leader
9:10 am - 9:40 amSrinivasan Yegnasubramanian (Johns Hopkins University, USA)
"The Double Edged Sword of TOP2B-Mediated Double Strand Breaks in Prostate Cancer"
9:40 am - 9:55 amDiscussion
9:55 am - 10:25 amCoffee Break
10:25 am - 10:55 amMarc Drolet (Université de Montréal, Canada)
"Interplay Between Type 1A Topoisomerases and R-Loops"
10:55 am - 11:10 amDiscussion
11:10 am - 11:40 amHannah Klein (New York University School of Medicine, USA)
"Multiple Roles of Topoisomerase I in Limiting Genome Instability Due to Misincorporated Ribonucleotides in DNA"
11:40 am - 11:55 amDiscussion
11:55 am - 12:05 pmSelected from Poster Abstracts: Tomas Aparicio (Columbia University Medical Center, USA)
"Repair of Topoisomerase 2-DNA Adducts by the MRN-CtIP-BRCA1 Pathway"
12:05 pm - 12:10 pmDiscussion
12:10 pm - 12:20 pmSelected from Poster Abstracts: Natassja Bush (John Innes Centre, United Kingdom)
"Quinolone-Induced Antimicrobial Resistance"
12:20 pm - 12:25 pmDiscussion
12:25 pm - 12:30 pmGeneral Discussion
12:30 pmLunch
1:30 pm - 4:00 pmFree Time
4:00 pm - 6:00 pmPoster Session
6:00 pmDinner
7:00 pm - 7:30 pmBusiness Meeting
Nominations for the Next Vice Chair; Fill in Conference Evaluation Forms; Discuss Future Site and Scheduling Preferences; Election of the Next Vice Chair
7:30 pm - 9:30 pmDNA Topoisomerase-Induced DNA Damage and Repair
Discussion Leader: Yves Pommier (National Cancer Institute, NIH, USA)
7:30 pm - 7:40 pmIntroduction by Discussion Leader
7:40 pm - 8:10 pmScott Keeney (Memorial Sloan Kettering Cancer Center, USA)
"Biochemical and Structural Studies of Spo11, a 'Broken' Topoisomerase"
8:10 pm - 8:25 pmDiscussion
8:25 pm - 8:55 pmIvan Marazzi (Icahn School of Medicine at Mount Sinai, USA)
"Topoisomerase I Inhibition Protects Against Pathogen-Induced Lethal Inflammation"
8:55 pm - 9:10 pmDiscussion
9:10 pm - 9:20 pmSelected from Poster Abstracts: Lorena Infante (Vanderbilt University, USA)
"'Oligonucleotide-Topoisomerase Inhibitors' Enhance Site-Specific DNA Cleavage Mediated by Human Type II Topoisomerases"
9:20 pm - 9:25 pmDiscussion
9:25 pm - 9:30 pmGeneral Discussion
Thursday
7:30 am - 8:30 amBreakfast
9:00 am - 12:30 pmDNA Topoisomerases in Cancer Therapy: Discovery and Development
Discussion Leader: Scott Kaufmann (Mayo Clinic, USA)
9:00 am - 9:10 amIntroduction by Discussion Leader
9:10 am - 9:40 amPeter Houghton (Greehey Children's Cancer Research Institute, USA)
"Camptothecins in Pediatric Oncology"
9:40 am - 9:55 amDiscussion
9:55 am - 10:25 amCoffee Break
10:25 am - 10:55 amDaniel Santi (ProLynx, LLC / University of California, San Francisco, USA)
"A PEG-SN-38 Pro-Drug that Releases SN-38 with Ultra-Long Half-Life, Low Cmax and Low Liver Exposure: From Concept to Clinical Trials"
10:55 am - 11:10 amDiscussion
11:10 am - 11:40 amNeil Osheroff (Vanderbilt University School of Medicine, USA)
"Human Topoisomerase II as a Target for Anticancer Drugs and Chemopreventative Compounds"
11:40 am - 11:55 amDiscussion
11:55 am - 12:05 pmSelected from Poster Abstracts: Laura Baranello (National Institutes of Health, USA)
"Direct Regulation of DNA Topology by the Transcription Machinery"
12:05 pm - 12:10 pmDiscussion
12:10 pm - 12:20 pmSelected from Poster Abstracts: Kostantin Kiianitsa (University of Washington, USA)
"Characterization of the DNA Trapped Proteome of the Human Cell"
12:20 pm - 12:25 pmDiscussion
12:25 pm - 12:30 pmGeneral Discussion
12:30 pmLunch
1:30 pm - 4:00 pmFree Time
4:00 pm - 5:30 pmPoster Session
5:30 pm - 7:30 pmCellular Responses to Topoisomerase-Targeted Therapies
Discussion Leader: Robert Van Waardenburg (University of Alabama at Birmingham, USA)
5:30 pm - 5:40 pmIntroduction by Discussion Leader
5:40 pm - 6:10 pmSue Jinks-Robertson (Duke University Medical Center, USA)
"Top1-Mediated Genetic Instability in Yeast"
6:10 pm - 6:25 pmDiscussion
6:25 pm - 6:55 pmPeter McKinnon (St. Jude Children's Research Hospital, USA)
"ATM, TDP1 and Topoisomerase Regulation in the Nervous System"
6:55 pm - 7:10 pmDiscussion
7:10 pm - 7:20 pmSelected from Poster Abstracts: Matthew Schellenberg (National Institute of Environmental Health Sciences, NIH, USA)
"ZATT SUMO Ligase Licenses Direct Reversal of Topoisomerase 2 DNA-Protein Crosslinks by Tdp2"
7:20 pm - 7:25 pmDiscussion
7:25 pm - 7:30 pmGeneral Discussion
8:00 pmDinner
Friday
7:30 am - 8:30 amBreakfast
9:00 amDeparture
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