Venomics: Drug Discovery from Nature's Deadliest

Venomics: Drug Discovery from Nature's Deadliest

Monday, November 4, 2013

The New York Academy of Sciences

Presented By

 

Spiders, snakes, scorpions, sea snails and leeches are not what come to mind when thinking of the products that stock a doctor's office or your local pharmacy. However, these animals produce a staggering number of compounds in their venom that are directly applicable for novel drug discovery. Encouraged by the substantial medicinal and fiscal success of the Bristol-Myers Squibb ACE-inhibitor and hypertension remedy, Captopril, and Elan's analgesic, Prialt® (Ziconotide) and their use to alleviate chronic pain in HIV and cancer patients, many pharmaceutical companies are now investing heavily in venom-based drug discovery programs. Due to ease of access, the majority of currently approved products were developed from snake venom proteins with distinct cardiovascular specificities, particularly those that target thrombin, fibrinogen and integrin receptors. However, rapid advances in proteomics, genomics and transcriptomics have leveled the playing field, providing affordable technology platforms that enable mining of venom proteins/peptides for drug discovery from species such as predatory marine snails and spiders, which produce venom in very small quantities yet are estimated to contain more than 10 million compounds available for drug discovery and development. New analgesics, anti-tumor agents and even agricultural pesticides await discovery and can be realized through an integrated approach combining genomic, proteomic, and transcriptomic data, which is being referred to as 'venomics'. Drug discovery and development activity will likely continue to rise as largely unstudied venomous animal lineages are investigated for novel lead compounds. This symposium will investigate integrated strategies necessary to harness the cornucopia of venom compounds using mass spectrometry, nucleotide sequencing, and synthetic chemistry.

Networking reception to follow.

This event will also be broadcast as a webinar. Please note:
Transmission of presentations via the webinar is subject to individual consent by the speakers. Therefore, we cannot guarantee that every speaker's presentation will be broadcast in full via the webinar. To access all speakers' presentations in full, we invite you to attend the live event in New York City where possible.

Registration and Webinar Pricing

Member$30
Student/Postdoc Member$15
Nonmember (Academia)$65
Nonmember (Corporate)$85
Nonmember (Non-profit)$65
Nonmember (Student / Postdoc / Resident / Fellow)$45

Silver Sponsor



Mission Partner support for the Frontiers of Science program provided by Pfizer

Agenda

* Presentation titles and times are subject to change.


Monday, November 4, 2013

8:30 AM

Registration and Continental Breakfast

9:00 AM

Welcome and Introduction
Jennifer Henry, PhD, The New York Academy of Sciences and
Mandë Holford, PhD, Hunter College, CUNY / American Museum of Natural History

9:15 AM

Keynote Presentation: Conus Venom Peptides and Constellation Pharmacology
Baldomero M. Olivera, PhD, University of Utah

10:00 AM

What Cyanobacteria Can Teach Us about Inhibiting Viral Infections
Carole A. Bewley, PhD, National Institute of Diabetes and Digestive and Kidney Diseases, NIH

10:30 AM

Coffee break

11:00 AM

Seeing the Woods for the Trees: Understanding Venom Evolution as a Guide for Biodiscovery
Bryan Fry, PhD, The University of Queensland, Australia

11:30 AM

Rapid MS-Based Methods for the Discovery of Venom Components
Beatrix Ueberheide, PhD, NYU Langone Medical Center

12:00 PM

Networking lunch

1:00 PM

Discovery and Delivery of Novel Therapeutic Peptides from Venomous Marine Snails
Mandë Holford, PhD, Hunter College, CUNY / American Museum of Natural History

1:30 PM

Mapping Neurocircuits with Genetically Encoded Membrane-Tethered Venom Toxins
Inés Ibañez-Tallon, PhD, The Rockefeller University

2:00 PM

The Atomic Structure of a K Channel–Scorpion Toxin Complex
Anirban Banerjee, PhD, National Institute of Child Health and Human Development, NIH

2:30 PM

Coffee break

3:00 PM

Evolutionary Leech Venomics
Mark E. Siddall, PhD, American Museum of Natural History

3:30 PM

Large-scale Venom-based Drug Discovery in the 21st Century: the VENOMICS Project and Beyond
Pierre Escoubas, PhD, VenomeTech

4:00 PM

Panel Discussion: Venomics: An Industry Perspective
Moderated by Steven S. Gross, PhD, Weill Cornell Medical College
Panelists include Yvonne M. Angell, PhD, Ipsen; Les P. Miranda, PhD, Amgen; Hazel H. Szeto, MD, PhD, Stealth Peptides Inc.

5:00 PM

Networking reception

6:00 PM

Close

Speakers

Organizers

Mandë Holford, PhD

Hunter College, CUNY / American Museum of Natural History

Dr. Mandë Holford is as an Assistant Professor in Chemistry at Hunter College and CUNY-Graduate Center, with a scientific appointment at the American Museum of Natural History. Her dual appointment reflects her interdisciplinary research, which combines chemistry and biology to discover, characterize, and deliver novel neuropeptides from venomous marine snails (cones snails, terebrids, and turrids) as tools for manipulating cell signaling in the nervous system. She has received funds from the National Science Foundation (NSF), the National Institutes of Health (NIH), and Alfred P. Sloan Foundation to support her independent research. Dr. Holford received her PhD in Synthetic Protein Chemistry from The Rockefeller University. In 2013 she was recently award the prestigious Camille Dreyfus Teacher-Scholar Award. In 2011 she was awarded an NSF CAREER Award, and named a 21st Century Chemist in the NBC-Learn, Chemistry Now series. She is an inaugural member of the World Academy of Young Scientist (WAYS), an organization sponsored by UNESCO and The Academy of Sciences for the Developing World (TWAS). She served on the Advisory Committee for Term Members of the Council on Foreign Relations and the Junior Council at the American Museum of Natural History. She is also a member of AAAS, The American Chemical Society, the American Peptide Society, and the New York Academy of Sciences.

Steven Gross, PhD

Weill Cornell Medical College

Steven S. Gross is Professor of Pharmacology, Director of the Mass Spectrometry Core Facility and Director of Advanced Training in Pharmacology at the Weill Cornell Medical College. The American Chemical Society recently awarded Dr. Gross with a 2011 award for "Achievements in Mass Spectrometry". His primary research interest is in cell–cell communication, with a focus on nitric oxide (NO) and reactive molecules as mediators of cell signaling. In the late 1980s, Dr Gross and colleagues made the initial identification of L-arginine as the precursor of NO in blood vessels. They were also first to establish that NOS inhibition elevates blood pressure in animals, demonstrating that NO plays a physiological role in controlling blood pressure and vascular tone. Since then, research efforts have been directed toward elucidating the enzymes and mechanisms that regulate NO synthesis in cells. His basic studies have provided fundamental insights into the therapeutic control of NO synthesis, resulting in core technologies for the creation of ArgiNOx Inc., a biotech start-up that seeks to develop novel NO-based drugs. Dr. Gross' research is supported in part by a MERIT Award from the NHLBI. He is a founder and Board Director of the Nitric Oxide Society and chairs the Steering Committee of the Biochemical Pharmacology Discussion Group (BPDG) at NYAS. Dr Gross received his PhD in Biomedical Science from the Mount Sinai School of Medicine in New York City.

Jennifer Henry, PhD

The New York Academy of Sciences

Keynote Speaker

Baldomero M. Olivera, PhD

University of Utah

Baldomero (“Toto”) Olivera was born in Manila and received his undergraduate degree in Chemistry from the University of the Philippines (summa cum laude).  He came to Caltech in Pasadena, California to do graduate work on the Biophysical Chemistry of DNA and did postdoctoral work in Biochemistry at Stanford. He returned to the Philippines to a faculty position at the Department of Biochemistry, University of the Philippines Medical School. In 1972, he moved to the University of Utah where he is presently a Distinguished Professor of Biology. His early research contributions include the discovery and biochemical characterization of E. coli DNA ligase, a key enzyme of DNA replication and repair that made the recombinant DNA revolution in Biology possible.

Dr. Olivera initiated the identification and characterization of biologically-active peptides found in the venoms of the predatory cone snails. A large number of peptide neurotoxins ("conopeptides") are present in these venoms, and their characterization led Olivera’s research group to a broad involvement with molecular neuroscience. Conus venom components are used to investigate the function of individual molecular components of nervous systems, particularly a class of protein complexes known as ion channels. In addition, the cone snail project has raised wide-ranging biological questions, from mechanisms of protein folding and post-translational modification, to gene organization and mechanisms of speciation. Several peptides discovered in Olivera’s laboratory have been developed by Biotech and Pharmaceutical companies as therapeutic drugs, three have reached human clinical trials and one (Prialt) has been approved by the FDA in the U.S. for the treatment of intractable pain. Additional applications of these compounds as therapeutics for heart attacks, strokes, epilepsy and other neuropathologies are actively being explored.

Speakers

Anirban Banerjee, PhD

National Institute of Child Health and Human Development, NIH

Anirban Banerjee got his MSc in Chemistry from the Indian Institute of Technology, Kanpur where he did research in supramolecular chemistry and total chemical synthesis of fullerene fragments. As a graduate student in Greg Verdine's lab in the Department of Chemistry and Chemical Biology at Harvard University, he combined tools and techniques from synthetic oligonucleotide chemistry, biochemistry and crystallography to study the problem of how a particular class of DNA repair proteins locate rare sites of damaged bases in DNA and discriminate between undamaged and damaged DNA. In his postdoctoral studies in the laboratory of Rod MacKinnon at The Rockefeller University, he focused his attention on various aspects of voltage-dependent K+ channels (Kv channels), including the mechanism by which small peptide toxins from the venom of poisonous animals target this important class of ion channels. In 2012, he started as an Earl Stadtman Investigator in the Cell Biology and Metabolism Program at the Eunice Kennedy Shriver National Institute of Child Health and Development (NICHD) in the Bethesda campus of the NIH. He is a recipient of the ACS Nobel Laureate Signature Award in Graduate Education, a post doctoral fellowship from the Damon Runyon Cancer Research Foundation and the NIH Director's Challenge Award in 2013.

Carole A. Bewley, PhD

National Institute of Diabetes and Digestive and Kidney Diseases, NIH

Dr. Carole Bewley received her PhD from Scripps Institution of Oceanography in Marine Natural Products Chemistry/Oceanography in 1996, and carried out postdoctoral research in the Laboratory of Chemical Physics at the National Institutes of Health. She joined the faculty of the Laboratory of Bioorganic Chemistry, NIDDK, NIH, in 2000 where she is currently a Senior Investigator and Chief of the Natural Products Chemistry Section and Deputy Chief of the Laboratory of Bioorganic Chemistry. She leads a multidisciplinary research program that focuses on discovery and structural studies of natural products and protein inhibitors that have therapeutic potential in the areas of antibiotics and viral entry inhibitors. For this work, she has been the recipient of the NIH Director's Award, the Paul Dowd Lectureship, and the Maryland Chemical Society, and is an inventor on numerous patents for discoveries in the area of anti-infectives. One of the most gratifying aspects of her job includes mentoring scientist/co-workers, especially in the chemical sciences. Dr. Bewley is an active member and reviewer for the American Chemical Society, and is currently a member of the Chemical Sciences Roundtable for the National Academy of Sciences, and an editorial advisory board member for the Journal of Organic Chemistry, Natural Product Reports, and Current Anti-Infectives.

Pierre Escoubas, PhD

VenomeTech

Dr. Pierre Escoubas is President and CEO of VenomeTech, a Biotech startup company located in the Sophia-Antipolis French research cluster. Dr. Escoubas obtained his PhD in Chemical Entomology at University Pierre and Marie Curie (Paris) in 1988, and worked as a post-doctoral associate at the University of Georgia (USA) before moving to Japan in 1989 as a research associate for the Japan Research and Development Corporation. In 1993, he joined the Suntory Institute for Bioorganic Research (SUNBOR) in Osaka to work on peptide toxins from animal venoms. He returned to France in 1998 to join the group of Prof. M. Lazdunski at the CNRS Institute of Molecular and Cellular Pharmacology in Sophia Antipolis, and as an Associate Professor at the University of Paris and University of Nice Sophia Antipolis until 2009.

He has also received business and entrepreneurship education at HEC Paris (Challenge+) and EM Lyon business schools. He founded VenomeTech in 2009 and has since been leading the company towards the development of innovative drugs from animal venom peptides.

He has implemented and is leading the FP7 European project VENOMICS (2011-2015, budget 6m€/8m$), a large-scale endeavor aiming at the development of novel drugs from animal venom peptides. Dr. Escoubas research interests include the discovery of novel peptide toxins from various venomous animals, biological mass spectrometry, peptide engineering and folding, ion channel molecular pharmacology, and the development of novel peptide therapeutics. He has organized symposia, workshops, training courses and lectures in peptide biochemistry and biological mass spectrometry. Dr. Escoubas has authored 78 research papers, and holds 8 patents.

Bryan Fry, PhD

The University of Queensland, Australia

Associate Professor Bryan Grieg Fry has published widely on venomous animals including cephalopods, centipedes, jellyfish, reptiles, scorpions, spiders, slow lorises and even vampire bats. His fieldwork has taken him to all of the continents, including collecting venomous octopuses in Antarctica. His discoveries include that the iconic Komodo Dragon is actually venomous. His research has led to the discovery of compounds useful as medicines, such as patenting taipan snake venom peptides for use in treating congestive heart failure.

Mandë Holford, PhD

Hunter College, CUNY / American Museum of Natural History

Dr. Mandë Holford is as an Assistant Professor in Chemistry at Hunter College and CUNY- Graduate Center, with a scientific appointment at the American Museum of Natural History. Her dual appointment reflects her interdisciplinary research, which combines chemistry and biology to discover, characterize, and deliver novel neuropeptides from venomous marine snails (cones snails, terebrids, and turrids) as tools for manipulating cell signaling in the nervous system. She has received funds from the National Science Foundation (NSF), the National Institutes of Health (NIH), and Alfred P. Sloan Foundation to support her independent research. Dr. Holford received her PhD in Synthetic Protein Chemistry from The Rockefeller University. In 2013 she was recently award the prestigious Camille Dreyfus Teacher-Scholar Award. In 2011 she was awarded an NSF CAREER Award, and named a 21st Century Chemist in the NBC-Learn, Chemistry Now series. She is an inaugural member of the World Academy of Young Scientist (WAYS), an organization sponsored by UNESCO and The Academy of Sciences for the Developing World (TWAS). She served on the Advisory Committee for Term Members of the Council on Foreign Relations and the Junior Council at the American Museum of Natural History. She is also a member of AAAS, The American Chemical Society, the American Peptide Society, and the New York Academy of Sciences.

Inés Ibañez-Tallon, PhD

The Rockefeller University

Dr. Ines Ibañez-Tallon is Visiting Associate Professor at the Rockefeller University and Group leader at the Max Delbruck Center for Molecular Medicine, Berlin. She studied Biology at the University of Barcelona, obtained her PhD in Genetic Sciences from the University of Milan and carried out postdoctoral studies at the Rockefeller University.

Mark E. Siddall, PhD

American Museum of Natural History

Mark Siddall, Curator, Division of Invertebrate Zoology Mark Siddall's research has focused on the evolutionary biology of a wide range of parasites, from single-celled microbes to leeches. Dr. Siddall now concentrates on researching Darwinian selection and diversity of hemotoxic venom proteins of leeches like Tyranobdella rex (T. rex), recently described from the Amazon. Siddall has led numerous field expeditions for the American Museum of Natural History. He is a professor in the Museum's Richard Gilder Graduate School and is principal investigator in the Museum's Sackler Institute for Comparative Genomics. In addition to serving as vice president of the American Society of Parasitologists, Siddall is also the curator of the Museum's exhibition Picturing Science: Museum Scientists and Imaging Technologies, and co-curator of the Irma and Paul Milstein Family Hall of Ocean Life and The Power of Poison opening in November of 2013. He received his PhD in Zoology from the University of Toronto.

Beatrix Ueberheide, PhD

NYU Langone Medical Center

Dr. Ueberheide joined the faculty of NYU as Assistant Professor in the Department of Biochemistry and Molecular Pharmacology and Director of the Proteomics Core. She has extensive experience in biological mass spectrometry, especially method development, mapping of post translational modifications, de novo sequencing, 'Bottom Up' and 'Top Down' strategies, as well as comprehensive protein characterization in complex mixtures. Dr. Ueberheide contributed to a wide range of studies from analyzing chromatin, characterizing venoms, to sequencing of complex antibody mixtures. She received her PhD in chemistry at the University of Virginia in the lab of Dr. Donald Hunt where she focused on the study of histone post translational modifications using classical 'Bottom Up' and also 'Top Down' strategies. She joined Rockefeller University in 2006 for her postdoctoral training with Dr. Brian Chait. There she developed de novo sequencing strategies for analysis of venom components and established techniques to study antibodies isolated from HIV infected long-term non-progressors. The current focus of her research is to develop advanced mass spectrometric techniques for the characterization, de novo sequencing and quantitation of proteins and their post translational modifications.

Panelists

Yvonne M. Angell, PhD

Ipsen

Yvonne Angell is Director of Chemistry at Ipsen. Yvonne earned her BS in Pharmacy and PhD in Medicinal Chemistry degrees at the University of Wisconsin-Madison. She completed her post-doctoral work at the University of Minnesota. Yvonne has 15 years of experience in the pharmaceutical industry. Past experience includes designing novel, constrained peptide libraries to inhibit protein-protein interactions as a scientist at Eli Lilly and Co., design and development of bead-based binding assays to identify new hits aimed at inhibiting protein-protein interactions at Genetics Institute (now Pfizer), and hit-to-lead optimization on several peptide therapeutic projects as a senior scientist at Affymax. Her current work at Ipsen is focused on discovery, design and engineering of novel, potent, selective lead peptide and peptide chimeric compounds for oncology and endocrinology targets. She has led several cross-functional project teams from early discovery through preclinical development.

Les P. Miranda, PhD

Amgen

Les Miranda is Director of Research in Therapeutic Discovery at Amgen, Inc. A graduate of the University of W. Sydney (Australia), he obtained his Ph.D. in synthetic peptide and protein chemistry from the University of Queensland (Australia). Les held a research position at the Carlsberg Laboratory (Denmark), and then served as an Associate Director at Gryphon Therapeutics (South San Francisco, USA) with Professor Stephen B.H. Kent, where he contributed to the development of methods for the total chemical synthesis and medicinal optimization of protein therapeutics. At Amgen, he is responsible for peptide and related hybrid discovery, and has supported numerous preclinical and early development programs. Les has led several cross-functional teams through various stages of drug discovery and development. During his career, Les has authored more than 50 publications and contributed to more than 10 issued patents.

Hazel H. Szeto, MD, PhD

Stealth Peptides Inc.

Dr. Szeto is a Professor of Pharmacology at Weill Cornell Medical College and Director of the Research Program in Mitochondrial Therapeutics. Dr. Szeto has extensive expertise in peptide-based drug design, pharmacokinetics, and preclinical drug development. She has developed a number of highly potent and selective opioid peptide analogs that are metabolically stable and can readily cross the blood-brain barrier. In 2004, Dr. Szeto made the original discovery that certain cell-permeable aromatic-cationic tetrapeptides selectively target and concentrate in the inner mitochondrial membrane. She recently discovered that these peptides target cardiolipin on the inner mitochondrial membrane, promote electron transfer through cytochromce c, enhance ATP production and reduce ROS generation. Dr. Szeto then evaluated their efficacy in protecting and restoring mitochondrial bioenergetics in numerous preclinical models of age-associated complex diseases, including cardiorenal diseases, metabolic diseases, neurodegenerative diseases, skeletal muscle weakness, and chronic pain. In 2006, Dr. Szeto founded Stealth Peptides International to take these “first-in-class” cardiolipin therapeutics from bench to bedside. The first drug candidate (Bendavia) has completed Phase 1 studies with intravenous and oral formulations, and is currently in Phase 2 clinical trials for acute cardiorenal ischemic injury and heart failure. An ophthalmic formulation is scheduled to enter clinical trial in early 2014. Dr. Szeto remains a full-time faculty member at Weill Cornell Medical College while serving as Scientific Consultant to Stealth Peptides. She received her MD and PhD in Pharmacology from Cornell University Medical College in 1977.

Sponsors

Silver Sponsor

Promotional Partners

International Society on Toxinology (IST)

Journal of Venom Research

Medicinal Chemistry

The Metabolomics Innovation Centre (TMIC)

MetaboNews

Nature

Toxicon

  • Technology Networks

Mission Partner support for the Frontiers of Science program provided by Pfizer

Abstracts

Keynote: Conus Venom Peptides and Constellation Pharmacology
Baldomero M. Olivera, University of Utah

The >10,000 species of venomous marine snails (superfamily Conoidea) have evolved sophisticated chemical strategies to interact with other animals in their environment. The venom from each Conoidean species contains more than 100 unique peptides, all honed by natural selection to interact with a specific molecular target in prey, predators or competitors of that species, resulting in >106 different venom peptides. Conoidean venoms contain multiple sets of peptides that act in concert on different molecular targets to achieve specific types of physiological perturbations, such as neuromuscular paralysis or excitotoxic shock. These functionally coupled sets of peptides are known as "cabals." Each cabal targets a cognate "constellations" of receptors and ion channels in a physiological circuit: different components of the "motor cabal" target specific components of the neuromuscular circuitry, including Ca channels in motor neurons, Na channels and nAChRs in muscle. The elucidation of venom-peptide cabals and receptor/ion channel constellations has inspired a new pharmacological paradigm called "Constellation Pharmacology", which we believe has the potential to transform both the discovery of novel pharmacological agents and the development of therapeutic drugs.
 

What Cyanobacteria Can Teach Us about Inhibiting Viral Infections
Carole A. Bewley, National Institute of Diabetes and Digestive and Kidney Diseases, NIH

Cyanobacteria, commonly referred to as blue-green algae, are ubiquitous on Earth and suggested to be one of the first life forms. Decades' of study on these unique bacteria has shown that they are veritable incubators for structurally complex natural products and proteins. Although some of these molecules are highly toxic in nature, others show promise for the treatment of cancer, neurological diseases and bacterial infections. An oddity among many groups of cyanobacteria includes the presence of novel sugar binding proteins that generally do not exist in other bacteria and eukaryotes. We have taken a multidisciplinary approach to thoroughly define the 3-dimensional structures of a number of these cyanobacterial proteins, and to determine the ways in which they can engage surface displayed glycan receptors. These traits endow these proteins with potent antiviral activities that will also be discussed.
 

Seeing the Woods for the Trees: Understanding Venom Evolution as a Guide for Biodiscovery
Bryan Fry, PhD, The University of Queensland, Australia

Natural compounds have been utilized for medicinal purposes since ancient times. The toxic secretions of venomous animals have evolved over millions of years of evolutionary time to induce paralysis and systematic breakdown of homeostasis in prey, in addition to aiding in defense against predators. In the process, a remarkable arsenal of biochemical components has been developed, including toxins with astonishing specificity and affinity for various types of cells and receptors, many of which participate in essential physiological pathways. Hence, venoms and toxins have been perceived as rich sources of novel biochemical compounds for use in drug design and development. Although biased towards a narrow range of taxa, modern toxinological research has focused on utilizing these fascinating biochemical compounds not only in elucidating the intricate mechanisms of life but also to aid in the development of lifesaving pharmaceutical drugs. Understanding the complex evolutionary mechanisms shaping different venom components is essential for the development of highly effective drugs. A multidisciplinary approach, spanning methods such as transcriptomics, proteomics, bioactivity testing and molecular evolution analyses has the potential to unravel the true biodiversity of toxins and provide invaluable information for drug design and development.
 

Rapid MS-Based Methods for the Discovery of Venom Components
Beatrix Ueberheide, NYU Langone Medical Center

Spiders are the most successful venomous predators on earth, with more than 42,000 species known – almost half of the species of all venomous animals. These venoms are one of nature's great diversity libraries of bioactive molecules and are very complex mixtures of proteinaceous and organic molecules, numbering in the hundreds, which target various receptors, channels and other molecular targets with varying degrees of specificity. This makes venom a very appealing source for potential therapeutics and insecticides. However, the extraordinary complexity of crude venoms and the lack of DNA databases for many of the organisms of interest and the limited venom amounts for many species present major analytical challenges. Here, we describe a combination of chemical modifications of spider toxins with orthogonal mass spectrometric fragmentation and an interactive search algorithm for the elucidation of primary toxin sequences directly from crude venom.
 

Discovery and Delivery of Novel Therapeutic Peptides from Venomous Marine Snails
Mandë Holford, Hunter College, CUNY / American Museum of Natural History

The pharmacological and biological diversity of peptide toxins from venomous marine snails present a vibrant and largely unexplored repository for investigating ion channels and receptors. To date the majority of snail peptide toxins characterized are from cone snails, conopeptides, however, more recent efforts have identified the peptide toxins of terebrids and turrids as equally viable for investigating the mechanics of the neuronal circuit. Dr. Holford's research applies inventive tools from chemistry and biology to: (1) identify disulfide rich peptide toxins from a venom source, (2) develop high-throughput methods for characterizing structure-function peptide interactions, and (3) produce novel peptide targets for therapeutic development.
 
Dr. Holford's presentation will highlight a dissociative peptide-drug delivery system applicable for investigating neuronal disorders such as pain. The first marine snail drug, ziconotide (Prialt®), used to alleviate chronic pain in HIV and cancer patients, is a major breakthrough that caused a paradigm shift in analgesic drug development. Despite ziconotide being a breakthrough drug, widespread application of ziconotide is limited due to its size (25 amino acids) and delivery method, an intrathecal delivery is required as ziconotide does not cross the blood brain barrier (BBB). The Holford lab has developed an alternative to intrathecal application of ziconotide by encapsulating it in a viral capsid nanocontainer for delivery across the BBB.
 

Holford lab website: raisenyc.org/Holford/Home.html
 

Mapping neurocircuits with genetically encoded membrane-tethered venom toxins
Inés Ibañez-Tallon, The Rockefeller University

We have developed a novel strategy for circuit mapping in the mouse nervous system using genetically encoded membrane-tethered toxins (t-toxins) that block the activity of ion channels and receptors in genetically defined neuronal cell types. These genetic tools are valuable both to determine the functions of these molecules in identified neurons, and to understand the contributions of specific cell types to circuits controlling behavior. For instance, t-toxin genetic inactivation of the voltage gated sodium channel Nav1.8 in nociceptive neurons has allowed us to determine that this ion channel is required for perception of noxious cold temperatures, while t-toxin selective blockade of the voltage gated calcium channel Cav2.2 has confirmed that this channel mediates inflammatory and neuropathic pain transmission. More recently, we have designed a universal Cre-mediated viral strategy to silence neurotransmission with t-toxins selective for Cav2.1 and Cav2.2 presynaptic calcium channels that mediate neurotransmitter vesicle release. This simplified system is effective for long-term silencing of neurotransmission and is now in use by more than 30 research groups for circuit mapping.
 

The Atomic Structure of a K Channel–Scorpion Toxin Complex
Anirban Banerjee, National Institute of Child Health and Human Development, NIH

Pore-blocking toxins from the venoms of poisonous animals inhibit voltage-dependent K+ channels (Kv channels) by plugging the ion-conduction pathway. MacKinnon and Milller suggested more than 20 years ago that these peptidic toxins electrostatically perturb ion-binding sites in Kv channels by presenting a positively charged residue close to it. Since then a large body of mutagenesis data has accumulated that has reinforced the initial hypothesis, yet there are no crystal structures of any Kv channel in complex with a pore-blocking toxin. We have solved the first crystal structure of a pore-blocking toxin in complex with an eukaryotic Kv channel, which is also the first crystal structure of any K+ channel in complex with a pore-blocking toxin. We faced a unique problem that arose from the symmetry properties of tetrameric potassium channels and we used synthetic peptide chemistry to solve it. The structure led to novel insights into the macromolecular recognition of Kv channels by these toxins and provides atomic rationale to a large body of experimental data. We solved the structure of the channel-toxin complex with different ions in the selectivity filter of the channel and these led insights into the unique properties of the selectivity filter of K+ channels.
 

Evolutionary Leech Venomics
Mark E. Siddall, American Museum of Natural History

Leeches depend on a diet of blood in each of freshwater, marine and terrestrial environments and one a variety of vertebrate host types. Bloodfeeding in leeches has long been of interest to biologists and medical practitioners alike. Their dependence on a diet of fresh blood has entailed an evolutionary history both of innovation and transformation of the hemotoxic venom profile of these remarkable annelids. While several isolated peptides have been subject to considerable stucy (e.g., hirudin, eglin, orgelase) only recently have the anticoagulant repertoires of a more comparative diversity of leeches been examined more comprehensively. Transcriptomic profiles of the venom glands of leeches are evolutionarily revealing only when considered across all major blood-feeding families, as opposed to a simple focus on commercially important or model organisms. In addition to mapping the historical patterns of evolutionary novelties, when furnished with a well-supported phylogentic hypothesis, patterns of Darwinian and purifying selection emerge at the molecular level.
 

Large-scale venom-based drug discovery in the 21st century: the VENOMICS project and beyond
Pierre Escoubas, VenomeTech

Animal venoms are large combinatorial libraries of biologically active peptides that encompass a wide variety of structures and pharmacological activities. As such, they represent an immense and largely untapped resource of novel molecules that can be developed as therapeutics and drug models. Exploration of the pharmacology and molecular diversity of venoms is now rapidly uncovering novel drug leads but the obstacles of physical size and venom complexity are daunting. Many venomous species are of microscopic size and venoms may be comprised of up to 1000 different peptides. As classical biochemical work based on bioassay-guided purification and chemical characterization cannot properly address those issues, novel paradigms had to be developed.
 
They have been implemented by VenomeTech in VENOMICS, the largest venom-based drug discovery program to date, funded under the European 7th Framework Program. The project, led by VenomeTech, involves eight partners from five countries. In VENOMICS, next-generation sequencing of venom gland transcriptomes coupled to mass spectrometry for de novo sequencing of peptides permits the deconvolution of venom complexity. Based on sequencing data, recombinant and synthetic production of peptide librariesallows forin vitro replication of venom molecular diversity. These “synthetic venom libraries” will then be used in drug discovery programs, dramatically quickening the pace of new lead generation.
 
However, the magnitude of the venom exploration challenge may only be fully addressed whenDNA sequencing techniques will allow for rapid and deep mining of thousands of animal species. It is therefore proposed that other forward-looking venom research programs should be developed today, with the vision of applying technologies to be developed in the next 20 years.
 

Travel & Lodging

Our Location

The New York Academy of Sciences

7 World Trade Center
250 Greenwich Street, 40th floor
New York, NY 10007-2157
212.298.8600

Directions to the Academy

Hotels Near 7 World Trade Center

Recommended partner hotel

Club Quarters, World Trade Center
140 Washington Street
New York, NY 10006
Phone: 212.577.1133

The New York Academy of Sciences is a member of the Club Quarters network, which offers significant savings on hotel reservations to member organizations. Located opposite Memorial Plaza on the south side of the World Trade Center, Club Quarters, World Trade Center is just a short walk to the Academy.

Use Club Quarters Reservation Password NYAS to reserve your discounted accommodations online.

Other nearby hotels

Conrad New York

212.945.0100

Millenium Hilton

212.693.2001

Marriott Financial Center

212.385.4900

Club Quarters, Wall Street

212.269.6400

Eurostars Wall Street Hotel

212.742.0003

Gild Hall, Financial District

212.232.7700

Wall Street Inn

212.747.1500

Ritz-Carlton New York, Battery Park

212.344.0800