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INTRODUCTION |
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 TOP INTRODUCTION American Society for...SymposiaAmerican Society for...SymposiaSpecial Sessions |
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A sampling of the sessions appears below. The Program and Abstract issue of The FASEB Journal contain additional details and are mailed to preregistrants in the U.S. and Canada before the meeting convenes. For up-to-date information, visit http://www.faseb/meetings.
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American Society for Biochemistry and Molecular Biology |
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TOPINTRODUCTIONAmerican Society for...SymposiaAmerican Society for...SymposiaSpecial Sessions |
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The efficacy, toxicity and duration of action of most drugs and other exogenous compounds consumed by man are determined by the activity and integrity of the enzymes responsible for catalyzing the biodegradation of these xenobiotics. In general, these enzymes convert lipid soluble compounds to water-soluble compounds that are subsequently excreted. Participants will discuss recent advances in the molecular mechanism of induction of drug metabolizing enzymes such as cytochrome P450 and flavin-containing monooxygenases as well as the pharmacogenetics and the genomics of human and mouse cytochrome P450. The symposium will feature a presentation of the crystal structures of the reaction intermediates of cytochrome P450 camphor and the latest information about electron transfer pathways between cytochrome P450 and its redox partners.
New Vistas in Therapeutics: From Drug Design to Gene Therapy
Organizers: M. Morris, F.C. Bennett, P.A. Velletri, A.
Trainor, S. Skarlatos, and V.J. Dzau
Speakers will discuss advances in small molecule drug discovery technologies used in modern drug discovery and advances in gene-based therapeutics. Topics will include a history of medicinals, natural products, rational drug design, combinatorial chemistry, antisense oligonucleotides, and gene therapy. The meeting brings together scientists from the pharmaceutical and biotechnology industry and university and NIH laboratories. Adequate time has been allowed for speakers to develop their topics and to provide a forum for discussion of issues currently facing researchers.
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Symposia |
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TOPINTRODUCTIONAmerican Society for...SymposiaAmerican Society for...SymposiaSpecial Sessions |
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Gene expression in eukaryotes is an enormously complicated process controlled at many levels, including gene silencing, messenger RNA transcription, RNA processing and maturation, protein translation, and post-translational modification/degradation. Recent advances in genomic sequencing, the development of arrays with which to measure mRNA levels, and the ability to work with large macromolecular assemblies, have transformed this important area of biomedical research. Participants will present results that illustrate new paradigms for studying gene expression in the post-genomic era. Topics will include regulation of transcription initiation in yeast and mammalian cells, the role of histone acetylation in gene expression, and the contributions of structural biology.
The Final Stage of Gene Expression: Control of Cell Function by
Regulated Proteolysis
Chair: R. J. Deshaies
Biological processes are controlled not only by the expression of new proteins, but also by the controlled, highly selective elimination of pre-existing ones. Over the past few years, it has become increasingly apparent that proteolysis plays a key role in cellular regulation and in human disease. For example, the cell division cycle is coordinated by the intimate interplay of cyclin-dependent kinases (Cdk) and ubiquitin/proteasome-mediated proteolysis of Cdk regulators. In contrast, apoptosis is triggered by the regulated activation of a family of intracellular proteases known as caspases. Caspases are stored within the cell as zymogens, and upon cleavage to the active form they promote apoptosis by degrading a broad range of intracellular proteins. As has been shown for the sterol regulatory element binding protein (SREBP) and Notch, specialized membrane-bound proteases can effect signal transduction by liberating the cytoplasmic domains of transmembrane proteins, which then diffuse to the nucleus to regulate gene expression. The processing of Notch may have particular relevance for human disease, because it is promoted by the presenilins, which have been implicated in the pathogenesis of Alzheimer’s due to their ability to promote the cleavage of amyloid precursor protein to form amyloidogenic peptides. The symposium will highlight these and other examples of how power of proteolysis is harnessed to control diverse biochemical pathways.
Chromatin Structure/Remodeling
Chair: R.E. Kingston
Modulation of chromatin structure is important to transcriptional regulation. Much of this modification occurs at the level of the nucleosome, whose structure inhibits binding and function of numerous nuclear proteins. Nucleosome structure can be modified covalently, by complexes such as acetyltransferases or de-acetylases, or non-covalently via interactions with chromatin modifying complexes. These complexes can alter chromatin structure to help establish either an activated or a repressed state. This session will cover sequence-specifc binding factors that can bind to nucleosomes and that might serve to initiate a remodeling of local chromatin, complexes that use the energy of ATP hydrolysis to remodel nucleosomes, acetyltransferase complexes, and complexes that stabilize repressive chromatin.
mRNA Metabolism
Chair: M. Moore
Events in the lifetime of an eukaryotic mRNA include transcription, capping, splicing, polyadenylatin, nuclear export, translation, and decay. Of these processes, the mechanisms of mRNA export and decay are arguably leas understood at the molecular level. Although the molecular mechanisms of other mRNA metabolic events have been intensely studied in isolation, it is becoming increasingly clear that all these processes are likely linked mechanistically in intact cells. For example, the action of spliceosomes in the nucleus can increase the efficiency of mRNA export, the efficiency of mRNA translation, and the rate of mRNA decay. Participants will report recent advances in the study of mRNA decay, including mRNA degradation by RNA interference, as well as progress toward understanding the mechanisms by which pre-mRNA splicing alters subsequent mRNA fate.
THEME II—CELL GROWTH, METABOLISM AND DISEASE
Chemical Approaches to Modulating Cellular Processes
Chair: C. Bertozzi
Fundamental studies of complex cellular processes can benefit greatly from the tools of chemistry. Synthetic molecules modeled after biological structures can be used to modulate the organization of receptors on the plasma membrane, the expression of biomolecules, and the interactions of cells with each other and their surrounding matrix. Participants will concentrate on the use of synthetic molecules and chemical principles to engineer new cellular functions and probe biological interactions, with a focus on such applications in the field of glycobiology.
Membrane Lipids: Regulation and Function
Chair: C. Kent
Phospholipids and sterols, major membrane lipids of eukaryotes, present several interesting problems to the membrane biologist. The lipids themselves have important roles in the membrane other than simply being a bilayer. Phospholipids may act as chaperones by critically influencing the folding and insertion of resident proteins into the membrane. Cholesterol can function in the formation of membrane domains with specialized composition and function, and such domains are highly enriched in molecules of signal transduction. Because of their multiple roles, the synthesis of these lipids must be highly regulated, particularly by mechanisms that are sensitive to the composition of membrane surfaces. Once the lipids are synthesized, they must be transported to multiple locations in the eukaryotic cell. Speakers will discuss developments in these areas that are leading to an integrated view of the function and metabolism of membrane lipids.
Hormonal, Transcriptional, and Neural Control of Energy Metabolism
Chair: M.D. Lane
Obesity is the most prevalent nutritional disorder of Western societies. Half of the adult American population is now considered overweight. This condition of "energy imbalance" is a major risk factor for Type 2 diabetes, cardiovascular disease, and other disorders that lead to increased mortality. Over the past several decades, there has been much evidence indicating that body weight is under physiological control. Only recently, however, has insight into the molecular mechanisms of this control been forthcoming. Participants will offer exciting new findings on the hormonal, transcriptional, and neural control of energy metabolism. These findings could lead to the identification of therapeutic strategies for the control of appetite and body weight.
Cell Cycle and Checkpoint Control
Chair: H. Piwnica-Worms
Checkpoints are signal transduction pathways that monitor the integrity and replication status of the genetic material before cells commit to either replicate (in S-phase) or segregate (in mitosis) their DNA. Checkpoints ensure the accurate reproduction and dispersion of the cells genetic material and defects in checkpoint pathways contribute to the onset and progression of human cancers. The DNA damage checkpoint monitors the integrity of the genome and arrests the cell cycle either in G1 before DNA replication (termed the G1 DNA damage checkpoint) or in G2 before mitosis (the G2 DNA damage checkpoint). In some instances, the G1 DNA damage checkpoint induces apoptosis rather than cell cycle arrest. Important components of the DNA damage checkpoint are the phosphoinositide (PI) 3-like kinases, including ATM and ATR in humans and Rad3 in fission yeast. Downstream of the PI3-like kinases lay the p53 tumor suppressor protein and the Chk1 and Cds1 protein kinases. Participants will discuss checkpoint control and how components of the DNA damage checkpoint, including ATM, Chk1 and Cds1, signal the cell cycle machinery to delay cell cycle progression.
Oxidized Lipids as Cellular Messengers
Chair: S.M. Prescott
The unsaturated bonds in fatty acids are rapidly oxidized, and the products increasingly have been recognized as signaling molecules. Recent developments show that phospholipids oxidized in this way can be signals themselves, or the modified fatty acid can be released as a signal. Alternatively, the oxidized lipids can covalently modify proteins, which alters their functions. The symposium will cover enzymatic and non-enzymatic mechanisms for generating oxidized lipids, novel signaling pathways (including those involved in disease processes), and structural, immunological, and functional characterization of lipid-modified proteins.
THEME III—SIGNALING
Hydrogen Peroxide as an Intracellular Signaling Molecule
Chair: S.G. Rhee
Many cell types produce hydrogen peroxide in response to a variety of extracellular stimuli that include cytokines, peptide growth factors, and agonists of G-protein coupled receptors. Receptor-mediated generation of H2O2 has been linked to the activation of transcription factors, protein kinases, phospholipases, to the inhibition of protein tyrosine phosphatases, to the triggering of apoptosis, and to modulation of ion transport. Specific inhibition of the H2O2 generation was shown to result in a complete blockage of receptor-dependent signaling. Because H2O2 is a small, diffusible, and ubiquitous molecule that can be synthesized, as well as destroyed, rapidly in response to external stimuli, it fulfills the important criteria for an intracellular messenger. Very little is known about the mechanism by which H2O2 is generated in response to receptor stimulation in nonphagocytic cells and the molecules on which H2O2 acts to propagate the signal. This session will report progress in these areas of research.
Subcellular Localization of Signal Transduction Complexes
Chair: J.D. Scott
As the molecular mechanism of signaling pathways become better understood, it is clear that protein-protein interactions are the glue that maintains the integrity of macromolecular signal transduction complexes. At the core of these complexes, scaffolding proteins position successive members of a signaling cascade in close proximity to each other. These include anchoring proteins, which position kinase and phosphatases in proximity to preferred substrates. Participants will discuss phosphateses in proximity to preferred substrates and present recent advances in understanding multivalent anchoring proteins, emphasizing kinases phosphatase signaling complexes, neuronal signaling complexes, and scaffolding proteins that segregate various modules of mammalian MAP kinase cascades.
Modeling of Cellular Networks
Chair: M. Simon
The availability of the complete genomic structure of a variety of microorganisms provides a list of components that are necessary to assemble a cell or a functioning organism. Thus, we have an opportunity to understand how these parts come together to form regulatory mechanisms, information processing pathways, and how they elicit cellular behavior. Quantitative models combined with incisive experiments and predictions provide the ultimate reality test. This session will provide insight into the role of modeling in understanding regulatory pathways and signal transduction cascades in microorganisms and in eukaryotic cells.
Mechanisms of Tumor Suppressors
Chair: H. Sun
Many tumor suppressor genes are first identified as the disease genes responsible for certain inherited cancer syndromes. Somatic mutations in these genes are subsequently detected in a variety of cancers. Investigating the functions of tumor suppressor proteins have provided important insight into the mechanisms by which cells control proliferation, differentiation, or apoptosis. Participants will report progess in elucidating the roles of tumor suppressors in regulating signal transduction, cell cycle progression, apoptosis, genome integrity, and DNA repair, and will discuss the functions of tumor suppressors in animal development.
Programmed Cell Death
Chair: J. Yuan
Apoptosis is a genetically regulated cellular suicide mechanism. Genetic studies of C. elegans programmed cell death has led to the identification of the three key components of this program: the survival gene that is critical for cell survival, the killer genes that carry out cell executions, and the engulfment genes that remove the dying cell by a neighboring cell. This genetic program is highly conserved through evolution. Recent researches have identified their homologues in organisms from Drosophila to human. Participants will present results on the recent progress in understanding the mechanism of apoptosis. Topics include new insights into the mechanism of Bcl-2 family function, an endoplasmic reticulum specific caspase pathway, and engulfment mechanism in Drosophila.
THEME IV—MACROMOLECULAR STRUCTURE AND FUNCTION
Single Molecule Function and Mechanism
Chair: J. Gelles
Biochemists want to learn about the behavior of individual molecules, but conventional biochemical methods can examine only the population-averaged properties of large molecular ensembles. However, the last decade has seen the development of a new group of single-molecule optical techniques capable of directly detecting chemical and conformational changes in single, isolated protein and nucleic acid molecules. This symposium will highlight research in which single-molecule methods have contributed to the solution of long-standing mechanistic questions in diverse fields including RNA catalysis, protein and RNA folding, transcription and membrane bioenergetics.
Macromolecular Machines/Assemblies
Chair: C. Guthrie
The machine metaphor has provided a powerful organizing principle for understanding the design and performance of the macromolecular complexes that carry out the basic steps of gene expression. The ribosome has long been known as a large ribonucleoprotein machine charged with carrying out the critical tasks of accurate decoding, catalysis (peptide bond formation), and the mechanical movement of mRNA relative to tRNA (translocation). Recent breakthroughsin ultrastructural analysis now allow the possibility of determining how the machine carries out each of these functions. One exciting answer likely to be forthcoming is whether any protein is close enough to the 23S rRNA peptidyl transferase center to make a direct contribution to catalysis. The relatively stable structure of the ribosome stands in dramatic contrast to the highly dynamic spliceosome, which must assemble anew around each intron from five snRNPs. Insight into the rationale for this unexpected design principle comes from the identification of RNA-dependent ATPases, which may promote RNA rearrangements while functioning as kinetic clocks. As with the ribosome, an important unanswered question is whether the spliceosome is a ribozyme. Recent evidence for the involvement of a protein at the catalytic core will be presented. Finally, the strategies of these two machineries can be compared and contrasted with the "transcriptosome," which can now be viewed as a mega-machine that not only carries out transcription, but also coordinates the recuitment of the RNA processing apparatus. This puts the transcription apparatus in a position to directly influence the regulation of all steps in gene expression.
Membrane Proteins: Structure and Stability
Chair: D.C. Rees
Integral membrane proteins participate in many important biological processes by facilitating the flows of molecules and information across membranes. Despite their functional significance, membrane proteins have been much less extensively characterized than water-soluble proteins due to the experimental challenges of mimicking the surrounding membrane and aqueous environments. The presence of both aqueous and non-polar phases should have important consequences for the structures adopted by membrane proteins and how these structures are stabilized in the bilayer. This session will discuss recent developments in establishing the basic principles that govern the structure and stability of membrane proteins.
Enzyme Structure and Function
Chairs: D. Ringe and L. Hedstrom
The question of how function derives from structure remains the fundamental mystery of enzyme catalysis. This session will spotlight recent structural insights into how enzymes catalyze reactions. Examples include the case a single enzyme active site, which catalyzes multiple chemical reactions; the combination of structure and mechanism to develop inhibitors with therapeutic potential; the elucidation of the structural basis of inhibitor selectivity, and the mechanistic basis of substrate specificity.
Multimodular Catalysis and Regulation
Chair: C. Walsh
The coordinated interaction of protein-protein interactions is central to the function of many pathways, from signal transduction to enzymatic assembly lines for polyketide and nonribosomal peptide antibiotics. The antibiotic biosyntheses represent multi-modular catalysts using thio-templates for chain elongation. Speakers will present approaches and examples of the logic of initiation, elongation, and termination in these assembly lines, and new information on the dynamics of chain growth and the architecture of some of the key catalytic and carrier domains.
BIOCHEMICAL EDUCATION SYMPOSIA
Multimedia in Biochemistry and Molecular Biology Education
Chairs: J. G. Voet and C. Rhodes
The past year has seen a proliferation of multimedia resources for teaching biochemistry and molecular biology, from CD- and Web-based images, animations, tutorials, lecture and lesson outlines to on-line testing and feedback. Speakers will focus on the use and assessment of some of these new resources. The poster session that follows will allow hands-on trial of these tools.
How to Get a Job in Academia
Chairs: C. Drennan and J. Wilker
Landing your first academic position as an assistant professor is a harrowing and, seemingly, random process. This session will attempt to demystify the faculty search procedure and help candidates find their first job. Invited speakers—young faculty who have gone through the job search recently and established faculty who have sat on several search committees—will present the perspectives of the larger, research-oriented universities and the smaller liberal arts colleges. The session organizers have surveyed biochemistry, biology, and chemistry departments nationwide on opinions of what makes a strong faculty candidate and the factors affecting hiring decisions. Results from this survey will be discussed.
Innovations in Biochemical Education
Chairs: J.E. Bell and H.B. White, III
Participants will present two important themes in undergraduate education in biochemistry and molecular biology: integration of material from a variety of subdisciplines and from labs and lecture, and the role that mentoring and career advising play in the educational process. Speakers will present various approaches for integrating material both horizontally and vertically in biochemistry curricula and courses, focusing on Web-based approaches for such integration. The roles that mentoring and assessment can play in the educational process and in career development of the students will be specifically addressed, with particular attention involving the student directly in the educational process rather than simply being the "consumer."
Assessing Change in Course Presentation –Panel Discussion
Chair: T. Woodin
A panel of three faculty members who have changed the course presentation and organization of large introductory classes, discuss the results of their efforts. How do they determine the effects of that change, what information concerning outcomes do they gather, and what have they found as the result of their efforts?
Involvement of Scientist in K-12 Education –Panel Discussion
Chairs: M.H. O’Leary and E.M. Kean
Professional scientists can play a variety of important roles in the improvement of K-12 education in the sciences. Although an occasional guest lecture in a classroom can be rewarding to the scientist, more prolonged contact between scientist and teacher or students can provide a more meaningful and enriching experience on both sides. Panel members representing both universities and the private sector will present a variety of models for supporting teachers and students, from small-scale programs involving only a few teachers and students to large-scale programs for an entire school or a major organization. We will examine these issues as an interaction of several cultures: the culture of science, the culture of schools, the culture of teachers, and the culture of the community. Members of the audience will also have a chance to share their experiences.
Preparing Minority Students for Post-Baccalaureate Education
in Biochemistry and Molecular Biology
Chair: T.D. Landefeld
This session focuses on the preparation of under represented minority students for post-baccalaureate education programs in biochemistry and molecular biology. Speakers will address factors that promote successful entry into, and graduation from, these postgraduate programs. Examples include effective advising/counseling, mentoring, available resources, university/laboratory environment, and appropriate coursework. The speakers will discuss their experiences with successful individual, programmatic, and institutional efforts.
Moving Your Research Ideas Along Towards a Commercial Reality
Chair: A.S. Dahms
This workshop is designed for individuals who consider themselves ‘business unsophisticates’. It is intended for molecular life scientists, including graduate students, postdocs, and faculty. The workshop will focus on entrepreneurial development and the process of starting and managing new biotechnology and life science companies. Learn whether your invention/discovery can be shaped into a business opportunity and how to validate and evaluate your business opportunity. Understand the key elements of building a business plan for attracting capital to build your business. Determine the best strategies for managing growth.
Women Scientists’ Mentoring Session/Reception
Organizer: A.J. Wolfson
Although the number of women studying biochemistry at the undergraduate level now equals or exceeds that of men, women are still underrepresented in the professorial ranks. This panel and reception are being organized as a forum for discussion of personal histories and strategies for increasing access for women in biochemistry. Several senior women will discuss their own experiences, and the reception will provide opportunities for forming mentoring partnerships.
SPECIAL SESSIONS:
ASBME/ABRF Symposium—Molecular Interactions
Chair: E. Eisenstein
The quantitative study of the interaction of biological macromolecules with each other and with small ligands has reemerged as a frontier as the need increases to address the strength, rates, and stoichiometry of molecular recognition, and as advances continue to be made in the methodologies to investigate these reactions. This symposium will focus on how fresh approaches to analytical ultracentrifugation, mass spectrometry, andsurface plasmon resonance biosensors can be used to characterize the solution behavior of biological macromolecules. Speakers will highlight essential fundamentals neededin order to employ these techniques successfully, and illustrate the types of questions that can be addressed, especially by novices, by presenting some state-of-the-art, practical examples.
Research Funding by the American Cancer Society
Chair: C.C. Widnell
The American Cancer Society (ACS) has recently introduced a major change in its Extramural Grant Program: Research Scholar Grants, awarded up to a maximum of $1,000,000 over 4 years will replace the current Research Project Grants. Postdoctoral Fellowships, awarded up to a maximum of $96,000 over three years, remain the same. ACS Program Directors, members of the peer-review committees, and a recent awardee will discuss the submission and review of applications, together with the characteristics that result in an application receiving a rating of "outstanding."
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American Society for Pharmacology and Experimental Therapeutics |
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TOPINTRODUCTIONAmerican Society for...SymposiaAmerican Society for...SymposiaSpecial Sessions |
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Functional genomics is a timely topic as the complete sequence of the human genome is currently being revealed and only through a thorough understanding of the structure and function of the genome will lead to the development of novel and highly effective therapeutic entities. Pharmacologists will work closely in the future with molecular biologists and protein biochemists to elucidate the function of specific genes and how this function relates to disease progression or suppression. Particpants will discuss the current methodology being used to study the genomic database and how genomic information can be applied to the treatment and management of human disease.
RGS Proteins
Organizers: H. Dohlman and
P. Sternweis
This colloquium is about regulation of G-protein signaling. The field of G-protein-coupled receptors (GPCRs) represents possibly the largest segment of pharmacological research. RGS proteins are a newly discovered component of the G-protein signaling pathway, originally identified through genetic analysis in yeast and nematodes. RGS proteins are now known to act as GTPase activating proteins (GAPs) for heterotrimeric G proteins, and thereby attenuate the activity of second messenger producing enzymes and ion channels. They may also serve as novel effectors in heterotrimeric G-protein signaling. This colloquium will address the physiological implications and selectivity of these important regulatory proteins at the cellular and whole animal level.
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Symposia |
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TOPINTRODUCTIONAmerican Society for...SymposiaAmerican Society for...SymposiaSpecial Sessions |
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Speakers will explore the exciting advances that have been made in the past few years regarding the role of arylamine N-acetyltransferases in drug toxicity and in disease causation after dietary, environmental, and occupational exposures to aromatic and heterocyclic amines. New studies show an important role for the arylamineN-acetyltransferases in genetic predisposition to cancer. This symposium will honor Wendell W. Weber, who has long been recognized as the most important contributor to the pharmacogenetics of arylamaine N-acetyltransferases.
Understanding the Behavioral Consequences of Gene Manipulations:
Integration of Genetically Engineered Animal Models into Behavior
Pharmacology Research
Chairs: G. Elmer and J. Barrett
Participants will examine how recent advances in molecular biology have enabled the production of a staggering array of genetically engineered animal models. The promise of these ‘tools’ has been to address questions related to the neuropharmacological basis of complex behavior. The cascade of neurochemical events and behavioral alterations produced by gene manipulation is under the domain of three previously distinct disciplines: molecular biology, behavior genetics, and behavioral pharmacology. The purpose of this symposium will be to provide a timely, systematic orientation to issues important in the planning, analysis, and interpretation of behavioral effects consequent to genetic manipulation.
THEME II—CELL GROWTH, METABOLISM AND DISEASE
Drug Metabolism in Animal Models of Human Disease
Chair: D. Christ
This symposium will discuss how the development and use of sophisticated animal models is an essential part of investigating mechanisms and discovering treatments for human disease. Historically, these models have been produced by surgical or chemical alterations of mature animals, thus disrupting homeostasis. Although the effects on the target organ or system have been characterized extensively, less attention has been paid to the effects these alterations produce on drug disposition and the model per se. Understanding the altered physiological, biochemical, and cellular responses in both new and old models of disease, and their projected relevance to human disease, is critical to the proper use of these models as surrogates. This symposium bridges the changes in physiological responses to gene regulation, using primarily models of endocrine disorders and infection.
Melatonin Receptors: Role in the Regulation of Sleep and
Mood Disorders
Chairs: M. Dubocovich and D. Krause
This timely symposium concerns how melatonin is an important modulator of mechanisms operative in central nervous system functions, and is involved in pathways and mechanisms that could be used as targets for the discovery and development of novel therapeutic agents. The discovery of novel neuronal and molecular mechanisms of melatonin actions in mammals helps to understand their role in human neurophysiology and psychiatric disorders and to develop selective treatments for circadian and non-circadian disorders. Participants will address aspects related to molecular biology and pharmacology of melatonin receptor subtypes.
Glucuronidation and the UDP-Glycosyl-Transferases (UGTs) in Drug
Therapy and Disease
Chairs: P. Wells and J. Ritter
Speakers will discuss the biological relevance of UGTs. Interindividual UGT variability likely plays an important role in drug efficacy and xenobiotic toxicity, as well as in certain diseases, which in some cases may be amenable to therapeutic manipulations, including gene therapy. The published information concerning UGTs and their biological relevance has been expanding rapidly in the last few years, as has the number of new investigators working in this area. Pharmaceutical companies also are becoming more interested in UGT pathway as it relates to the efficacy and potential toxicity of their drugs.
COX-2 and Cell Growth: New Insights
Chairs: S. Lotersztajn and P.D’Oleans-Juste
In the past few years, the comprehension of the role of cyclooxygenases (COX) in physiology and physiopathology has greatly improved. In particular, the role of COX 2 isoform in cell growth, and its involvement in cancer, atherosclerosis and fibrosis is emerging. Participants will concentrate on the advances in the pharmacology of COX-2 inhibitors and their use as therapeutic agents in these pathologies.
Protein-Based Pharmacokinetic Antagonist for the Treatment of Drug
Abuse
Chair: S. Owens
Medications development for the treatment of drug abuse and chemical dependence is problematic. Successful therapy is often hindered by the lack of useful antagonists for many of these chemicals and by the extensive distribution of these chemicals out of the bloodstream. Recent advances in immunotherapy, enzymology, and large-scale production of biological reagents suggest these novel approaches could be beneficial in the treatment of drug abuse. These medications function as pharmacokinetic antagonists and are designed to reverse the effects of drug overdose and/or help blunt the reinforcing effects of drugs of abuse. Presentations will cover molecular design of antibodies, large-scale production of protein medications, pharmacokinetic and pharmacodynamic relations for optimizing therapeutic strategies, and preclinical testing of medications.
THEME III—SIGNALING
Accessory Proteins and GPCR Signaling
Chair: S. Lanier
This symposium will expand current thoughts concerning mechanisms of signal propagation by G-protein-coupled receptors. The seven-membrane span hormone receptor coupled to heterotrimeric G-proteins represents one of the most widely used systems for information transfer across the cell membrane. Signal processing via this system likely operates within the context of a signal transduction complex somewhat analogous to that observed upon binding of agonists to single membrane receptors.
Rho as a Mediator of GPCR Signaling
Chair: J. Brown
Presenters will consider mechanisms controlling Rho activation, the evidence that Rho is required for a variety of GPCR-induced responses, and recent insight into how Rho is activated by GPCR agonists. This growing research area is likely to define a previously unknown sequence of molecular interactions critical to the process of G-protein-mediated cell signaling.
Cannabinoids: A Neurotransmitter System with Multiple Functions
Chair: J. Moersbaecher
This symposium is on the current thinking regarding cannabinoid system function as studied in rodents, nonhuman primates, and humans. Presentations will address major issues concerning the discovery and functioning of the cannabinoid system by leaders in different phases of cannabinoid research. Topics include new information regarding mechanisms of receptor activation and inactivation as well as more potent ligands and antagonists; the role of the endogenous cannabinoid ligand anandamide; mechanisms of cannabinoid receptor signaling and synaptic modulation; at the behavioral and cognitive level, the consequences of cannabinoid receptor activation from studies in rodents, nonhuman primates; and effects in humans as assessed by performance and noninvasive brain imaging techniques.
Physiological Significance and Cross-talk of bHLH-PAS
Proteins
Chairs: L. Birnbaum and M. Santostefano
Scientists will share information and expertise on the cross-talk between bHLH-PAS signaling pathways and the effects on cell function and biological rhythms and information and expertise on the modulation of bHLH-PAS proteins and effects on cell function.
Signaling by G-Protein ß/
Subunits
Chairs: J. Garrison and M. Whiteway
Participants will present the status of our current and emerging
understanding of the function of the ß/ subunit in cell signaling.
Roles of Phospholipase D in Signal Transduction
Chairs: K. Meier and M. Frohman
Although recent advances in the molecular characterization of PLD isoforms have greatly expanded the scope of this area of research, many questions remain. Participants will discuss which isoforms of PLD are responsible for agonist-mediated effects and what are the roles of PLD isoforms in signal transduction.
Regulation of Adenylyl Cyclases
Chairs: J. Hanoune and P. Insel
This symposium is designed to update several new aspects of adenylyl cyclase regulation. Adenylyl cyclase is widely recognized as the critical catalyst in regulation of cyclic AMP formation.
Ecto-Nucleotidases: Molecular and Biochemical Properties and their
Impact on Nucleotide Receptor Signaling
Chairs: R. Nicholas and J. Boyer
Investigators who study the enzymatic and structural properties of ecto-nucleotidases and those who study the role of the ecto-enzymes in P2 receptor signaling, differentiation, and development will discuss recent advances in these areas.
THEME IV—MACROMOLECULAR STRUCTURE AND FUNCTION
Biology of 
2-Adrenergic Receptors
Chair: S. Liggett
Participants will consider how these receptors function, to drug design and discovery, to physiology. These receptors have presented a significant challenge in understanding structure/function relationships, regulation, signal transduction pathways, and the roles of the different subtypes in normal physiology, pathologic conditions and the response to therapeutic agents. Recent developments over the last few years include delineation of structural requirements for ligand binding, receptor trafficking, regulation by various kinases, coupling to multiple G-proteins and effectors, and successful ablation of each subtype in knockout mice.
Molecular and Cell Biology of the Opioid Receptors
Chair: H. Loh
This symposium will bring the audience up to date on the advances of the molecular and cell biology of the opioid receptor and will bring together various approaches to study the receptor function, from the molecular biological mutagenesis studies to the whole animal studies using transgenic animals.
Novel Concepts in Cardiac ß-Adrenergic Receptor Function
Chairs: F. Pecker and T. Hebert
This symposium will be devoted to developments in Cardiac ß-adrenoceptors. They serve as references to protein G-coupled receptors since specific tools and cellular or animal models have been developed for their study and that of the intracellular signaling pathways linked to their activation.
Regulation of Cardiac Calcium Channels by Arachidonic Acid and its
Metabolites
Chair: R. Rosenberg
This symposium will focus on the direct and indirect regulation of L-type and T-type cardiac calcium channels by arachidonic acid and its metabolites. A growing field of research interest is on the topic of ion channel regulation by arachidonic acid and its epoxygenase metabolites.
Toxins as Probes of Structure and Function of Ligand and
Voltage-Gated Channels
Chair: P. Taylor
This symposium will focus on how a wide variety of toxins in marine and terrestrial animals have yielded not only information on which subtype of receptor channel is the target, but also structural characteristics of the target site. The speakers will consider toxins from the cone snail, venomous snakes, sea anemones and coral, and show how these toxins have evolved, how they are biosynthesized from precursors, how minor variations in their structures affect pharmacologic activity, how they recognize in molecular terms their target sites and what can be learned in structural terms from the interactions at the target sites. Several cases have clinical uses and one speaker will discuss progress in the use of conantokins in the treatment of severe seizure disorder.
Public Affairs Symposia
Implications for Biomedical Research of Proposed
Changes to the NIH Peer-Review System
Chair: P. Taylor
The NIH peer-review process is undergoing a major overhaul. What will be the implications of this reorganization for the future of basic and clinical pharmacology, biochemistry, and molecular biology? Will the CSR reorganization effectively encourage important research into drug discovery and development? Can this reorganization help facilitate research that will continue to contribute advances in defining basic biological mechanisms at the molecular, cellular, organ, and clinical levels? Panelists will discuss these issues and participate in a question-and-answer session.
Safety Pharmacology: Functional Evaluation of New Chemicals
for Potentially Life-Threatening Effects
Chairs: A.S. Bass and L.B. Kinter
Safety Pharmacology is emerging as a critical discipline in the development of new pharmaceuticals as scientists realize that traditional methods of toxicity testing are inadequate for identifying all potentially life-threatening pharmacological effects of new compounds. Safety Pharmacology seeks to identify the effects of new chemicals on critical organ functions prior to first human exposure, or to understand a significant pharmacodynamic outcome observed in non-clinical or clinical trials, as a means of bringing a perspective of risk assessment to the safe use of a drug in man.
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Special Sessions |
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An internationally representative group of speakers will discuss training, networking, and other opportunities for postdoctoral fellows in the international community. Interested undergraduate and graduate students, postdoctoral fellows, mentors, and training program directors are invited to the convocation and the reception immediately following.
Teaching Institute 2000
Integrative Approach to Medical Education: Foundations,
Methods and Outcome Assessment
Chair: C. Davis
This program will deal with the integrative approach to medical education. Speakers will discuss specific learning behaviors relevant to undergraduate medical education, teaching methods and curricular designs that foster integrative learning behavior in undergraduate medical education in the basic sciences, and address the application of cognitive learning behaviors in the assessment of student’s problem-solving skills in the basic sciences.
A Balanced View of the Pharmacological Treatment of Menopause
Chair: L. Dwoskin
This session will be an overview of the various effects attributed to estrogen hormone replacement therapy, including the cardiovascular and neuroprotective effects of estrogen and recent studies on the role of estrogen therapy on cognitive function in postmenopausal women.
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