1998 ASBMB Annual Meeting May 16–20, 1998 Washington, D.C.

	INTRODUCTION

TOP INTRODUCTION Symposia Biochemical Education Symposia Satellite Sessions Special Sessions

	Symposia

TOP INTRODUCTION Symposia Biochemical Education Symposia Satellite Sessions Special Sessions

 
Theme I: Genomes
Predicting Function from Genomes
Chair: D.L. Brutlag

Predicting biological function from genome sequences is accomplished by using several methods. Translated open reading frames from genome studies are compared with existing proteins by sequence similarity methods such as FASTA, BLAST, or Smith-Waterman alignment. Novel open reading frames are also compared with whole families or superfamilies of proteins using consensus sequences, sequence blocks or probabilistic models such as profiles or hidden Markov models. All of these methods address the problem of maintaining a high sensitivity of genome search (i.e., find all possible biological functions) and a high specificity of the search (make no false predictions) simultaneously. Speakers will present the leading methods for detecting biological function in genome-size databases, minimizing false predictions and maximizing the biological information derived from genome sequences.

Predicting Function from Sequence
Chair: B. Honig

The vast quantity of full-length protein sequence date currently being produced by various genome projects poses new computational and theoretical challenges. A central goal is to identify function given a primary sequence. Methods of sequence comparison aimed at identifying related proteins of known function are undergoing continuous development and are being increasingly enhanced by the incorporation of three dimensional structure information. Recent attempts to organize proteins into sequence and structural families and the relationship between the two are providing functional insights not available from either type of data alone. In addition, physical and chemical properties of protein surfaces can reveal a new class of functional homology relationships that are just beginning to be exploited. This session will report progress in each of these areas and discuss the further integration of sequence and structure information into functional analysis.

Unstable DNA and Triplet Repeat Diseases
Chair: R.D. Wells

A veritable explosion is taking place in our understanding of the human genetics, biochemistry, and DNA structural issues related to human hereditary neurological diseases. Also, the non-Mendelian expansion process that elicits these disease manifestations (anticipation) is under intense investigation. The molecular basis of a dozen human genetic disorders (including fragile X syndrome, myotonic dystrophy, and Huntington's disease) have been partially established. The expansion of simple triplet repeats occur upon passage of an expanded repeat in the chromosome to offspring. Biochemical studies are providing important clues regarding the etiology of these devastating diseases.

Genome Structure and Evolution
Chair: J.C. Venter

The sequencing of H. influenzae ushered in the era of whole genome sequencing. The result is then to expand this field beyond human genome efforts to include the sequencing of microbial and plant organisms, thereby providing critical information to understand the most fundamental aspects of biology utilizing the field's most revolutionary tool. This session will provide an oversight of how genome-scale tools are used and the efforts applied in the areas of human, microbial, and plant genomics.

Theme II: Regulation of Gene Expression
Chromatin and Structure
Chair: T.J. Richmond

DNA in eukaryotic cells is organized as chromatin. The fundamental repeating unit of chromatin is the nucleosome, occurring approximately every 200 ± 40 bp throughout every eukaryotic genome. Nucleosomes, both in nucleofilaments and in higher-order-structure assemblies, are responsible for ordering and compacting DNA, and as a consequence, play an important role in the regulation of gene expression. Participants will present results that newly illuminate chromatin structure/function interdependencies. Topics will include the acetylation and deacetylation of the N-terminal histone tails emanating from nucleosomes; the characteristics of an ATP-driven, chromatin remodeling factor; and the high resolution X-ray structure and biophysical properties of the nucleosome core.

Mechanisms of Transcriptional Control
Chair: R. Roeder

The transcription of protein-encoding genes is mediated by RNA polymerase II and cognate accessory factors (basal transcription machinery) that function through common core promoter elements. Transcription is further regulated by gene- and cell-specific factors that bind to distal promoter or enhancer elements and, either directly or through newly described co-activators, enhance the function of the basal machinery on specific target genes. Recent biochemical and genetic studies have enhanced markedly our understanding of the structure and function of the eukaryotic transcriptional machinery, including the involvement of a complex array of RNA polymerase II accessory factors and coactivators and their assembly and function within large multicomponent complexes. Speakers will emphasize structural aspects of the basal transcription machinery and the identification and functional analysis of coactivators (or mediators) in both yeast and mammalian cells.

Repression and Activation
Chair: M. Levine

This symposium will focus on the role of upstream transcription factors, both activators and repressors, in the establishment of cell-specific patterns of gene expression in several different embryonic systems, including C.elegans, Drosophila, and mice. Speakers will emphasize the integration of complex regulatory information to generate simple, on/off patterns of gene expression. Topics will include recent studies on general corepressors and coactivators that are recruited to the DNA template by sequence-specific transcription factors, and mechanisms of repression.

Cell Cycle
Chair: D. Beach

The Machinery of DNA Replication
Chair: P.H. von Hippel

There is great progress in understanding the functional details of the processes and control of DNA replication in various organisms at the molecular level. This symposium will describe some of these advances. In the simpler (elongation) stages of the replication process, it is now clear that these systems contain three sub-assemblies that interact to drive and regulate the elongation phase in organisms at all levels. These sub-assemblies consist of two copies of the replication polymerase itself which, assisted by a single-stranded binding protein, catalyze the template-directed synthesis of the leading and lagging strands of new DNA. The processivity of the synthesis by these polymerases is controlled in part by a `sliding clamp' that holds the polymerase to the DNA at the primer-template junction and is loaded onto the DNA (and the polymerase) by an ATP-dependent clamp-loading complex. Finally, a primosome containing a primase to synthesis RNA primers for lagging strand synthesis and a helicase to catalyze opening of the `parent' DNA is also required in all organisms. The interactions of these three sub-assemblies in directing leading and lagging strand DNA synthesis will be discussed at several levels. In addition, progress at the molecular level is also being made as to understanding the more complex process of initiation of DNA replication at DNA origin sites.

Theme III: Signal Transduction
G Proteins
Chair: R. Iyengar

Understanding signal transduction through G proteins is currently at the level of molecular interactions between the signaling components. This symposium will highlight recent advances in our understanding of the molecular interactions that underlie the regulation of GTP hydrolysis and signal transfer from G protein subunits to effectors.

Virus Capture of Signal Transduction
Chair: C. Gerard

For viruses to propagate, they must contend not only with piracy of the host cells transcriptional apparatus but also with both the innate and acquired arms of the immune system. Pox viruses, herpes viruses, and retroviruses have all been shown to manipulate the host response to infection. In this symposium, presentations will underscore current knowledge as to the connection of the chemokines with viral pathogenesis, the stealth strategies of HIV, and the mechanics of cytomegalovirus control of gene expression.

Structural Basis for Transmembrane Signaling
Chair: J. Noel

The mechanism by which information is parsed from the outside to the inside of the cell across the plasma membrane or within the cell across intracellular membranes is of fundamental importance in the regulation of cell growth and activity. Participants will discuss structural approaches to understanding the molecular mechanisms of transmembrane signaling. In addition, new exciting work in the area of membrane processing will be presented. The goal of the symposium is to lend a molecular view to the ways in which cells have evolved to deal with a multitude of signals that ultimately must be converted or transduced into biochemical signals within the cell.

Integration of Signaling Pathways
Chair: B. Errede

Signaling Responses to Stress
Chair: G. Johnson

Cells have developed strong defense mechanisms to protect themselves against stresses including changes in osmolarity, temperature, toxins, and irradiation. Among the responses to stress stimuli are the activation of specific signal transduction pathways. These signals include protein and lipid kinases that are involved in the control of cellular proliferation, metabolism, and apoptosis. The integration and magnitude of these intracellular signal responses can contribute to cellular damage, the activation of repair mechanisms, and the decision to live or die. The participants in this session will describe different signaling systems used by the cell to respond to different stress stimuli. The stress responses have been defined in cells and reconstituted in cell-free extracts. The characterization of the signal transduction pathways controlling cellular stress responses should provide new strategies in the future to prevent tissue damage after stress insults to the animal.

Theme IV: Molecular Structure and Function
Structural Analysis of Signaling Molecules
Chair: S. Sprang

The techniques of X-ray crystallography and NMR, combined with structure-function analyses, have now provided detailed views of signaling molecules in more than one functional state. Symposium participants will discuss the architectures and mechanisms of heterotrimeric G-proteins, SH2 domains, and Src-family tyrosine kinases. Emphasis will be on understanding how the structural modules of signaling molecules provide specificity and how dynamical aspects of the structures allow the molecules to respond quickly to changing input signals.

RNA Structure and Modeling
Chair: J.A. Doudna

Ribonucleic acid molecules are integral parts of the cellular machinery for protein biosynthesis, RNA processing, chromosome end replication, and protein transport, and some RNAs are catalysts (ribozymes) in their own right. Due to this abundance of biologically important RNAs and the development of technical advances to study them, RNA structural biology has come of age. It is now clear that RNAs are capable of a level of structural complexity that was once thought to be confined to proteins. Learning the rules for RNA structural assembly and folding is key to understanding the multitude of biological functions of this versatile nucleic acid. Participants discuss recent RNA structure determinations, the kinetics and thermodynamics of RNA folding, and approaches to RNA structural modeling.

Protein Folding in Health and Disease
Chair: J.A. King

The full expression of the information encoded in genes depends on the linear amino acid sequences of newly synthesized polypeptide chains folding up into unique three dimensional protein structures. Failures in protein folding processes are emerging as an important locus of human disease as well as an aggravating problem in biomedical research and the biotechnology industry. Speakers in this symposium will report on human diseases due to protein misfolding, recent advances in chaperonin function, which aid protein folding processes, aspects of misfolded states which constrain protein folding pathways, and properties of partially folded intermediates in protein folding.

Membrane Protein Structure and Function
Chair: W. Kühlbrandt

Detailed knowledge about the three-dimensional structure of membrane proteins is the prerequisite for understanding cellular processes that involve biological membranes. Yet, only comparatively few membrane protein structures are known, due to the difficulty of growing crystals of these proteins suitable for X-ray crystallography or high-resolution electron microscopy. This symposium will focus on membrane proteins that adopt different conformations to perform their specific tasks. Connexins form gap junctions, which mediate cell-cell communication. Structural changes that accompany the opening and closing of the gap junction channel have been investigated by electron microscopy. Two different forms of the mitochondrial bc₁ complex that appear to be important for electron transport across the membrane have been determined by X-ray crystallography. Finally, electron crystallography of two-dimensional crystals has revealed a new conformation of a P-type ATPase that pumps protons through the plasma membrane. These three examples provide fascinating new insights into the molecular mechanisms of membrane transport and biological energy conversion.

Enzyme Mechanisms
Chair: G.L. Kenyon

The study of enzymic mechanisms has advanced remarkably in the last decade, largely due to concurrent advances in molecular biology and protein crystallography. Recombinant DNA techniques, such as cloning, overexpression, and site-directed mutagenesis, have provided for the first time substantial quantities of biochemically interesting proteins, for example. And new protein crystallographic techniques, such as the use of area detectors, synchrotron radiation sources, and low-temperature methods, have provided a plethora of high-resolution, three-dimensional structural information about these proteins. Combined with these techniques have been steady and important advances in the mechanistic use of enzyme kinetics, both steady-state and pre-steady-state, and in sophisticated mechanistic uses of isotope effects, viscosity effects, and various forms of spectroscopy. Most recently, the field of informatics, specifically using sequence alignments of open reading frames (ORFs) available from various genome projects, has begun to have a profound effect on mechanistic enzymology. These sequence alignments alone can provide important clues as to the likely mechanistic relationships among sets of related proteins. The symposium will illustrate how these approaches have permitted new levels of insight into some mechanistic problems.

Viral Structure and Assemblies
Chair: C. Carter

Homo- and heteromeric protein associations control many processes that are fundamental to biology. Viral assemblies offer unequalled opportunities to identify determinants of protein association and dissociation because they often 1) can be reversibly assembled in vitro under both physiological and non-physiological conditions; 2) recombinant or authenic subunits can be used, and 3) these subunits can be genetically manipulated. Several viral capsids are now understood in atomic detail because they possess these tractable features. Examination of viral assemblies displaying quasi equivalence has suggested that the individual subunits and the subunit associations display conformational polymorphisms that depend on some type of molecular switching mechanism, a property shared with proteins involved in signal transduction. Incipient characteristics of these switches are multicomponent and sensitive to the assembly/disassembly environment. Participants will discuss structures of viral capsids and the influence on subunit interactions of segments of the capsid subunit, ions, nucleic acids and cellular proteins.

	Biochemical Education Symposia

TOP INTRODUCTION Symposia Biochemical Education Symposia Satellite Sessions Special Sessions

 
Inside and Outside the Large Class Setting: Teaching and Learning Biochemistry
Cochairs: C. Rhodes and J. E. Bell

Workshop: Introduction to Problem-based Learning in Undergraduate Biochemistry
Cochairs: H.B. White, III and D.E. Allen

Problem-based learning in undergraduate courses is attracting attention as a way to get students to think critically by analyzing and developing solutions to real world problems. Students work together in small groups during class time and seek relevant information between classes in a variety of resources beyond their textbooks. This approach to learning addresses many of the perceived deficiencies of traditional education.

Undergraduate Study Abroad in Biochemistry and Molecular Biology
Chair: J.E. Bell

This roundtable session will highlight many established study abroad programs that provide opportunities for undergraduates in biochemistry and molecular biology to out of the cuontry, and often incorporate some research experience during their stay. The discussion will also focus on how such opportunities can be created and what the student and home institutions gain from such programs

New Ways of Assessing
Cochairs: T. Woodin and A.J. Wolfson

Students and faculty are beginning to reap the benefits of faculty time and creative effort invested in the design of courses that help students gain solid concepts and skills in biochemistry and molecular biology. The challenge now is to validate that effort with assessment strategies that give students and faculty a sense of what is being learned and that reflects the way students are taught. This session will concentrate on a variety of methods that are being developed. There will be specific examples and time to experiment with them.

Student Research in Undergraduate Institutions: How, When and Why?
Cochairs: J.E. Bell and M. Koszalka

Participants will discuss ways in which student research can be incorporated into undergraduate programs: How research groups can be accommodated into busy teaching schedules, how collaborative research interactions can foster interest in research and potentiate the learning experience of undergraduates, and how research ideas and projects can be incorporated into didactic teaching laboratories. Invited speakers will address specific issues such as Senior thesis research projects and the involvement of first-year students in research and funding opportunities to support student research in undergraduate institutions.

Career Options in Biochemistry and Molecular Biology
Chair: C. Drennan and C. Rohlman

This session will feature Ph.D. scientists who are employed in work other than academic research, including panelists from the fields of science writing, patent law, lobbying, government service, association management, and other avenues where having a science Ph.D. will stand one in good stead.

The Role of Scientific Societies in the Changing Environment of Affirmative Action
Cochairs: T.D. Landefeld and M. George

This session focuses on an issue in higher education of special importance, given recent court decisions regarding affirmative action that have resulted in dramatic drops in the numbers of minority students enrolled in medical schools. Scientific societies can and do have a role to play in assuring that careers in science are open and available to all of our country's citizens. The keynote address will be based on David Burgess's article in The Chronicle of Higher Education entitled "Barriers to Graduate School for Minority Group Students" and will be delivered by Dr. Burgess.

	Satellite Sessions

TOP INTRODUCTION Symposia Biochemical Education Symposia Satellite Sessions Special Sessions

 
Molecular Characterization of Membrane Lipid Metabolism
Organizers: C. Kent and G.M. Carman

Keynote Addresses: C.R.H. Raetz and E.A. Dennis

Membrane lipids are key molecules that contribute to the structural definition of cells and that participate in the regulation of many cellular processes. Lipids serve as signaling molecules and as reservoirs of lipid second messengers. This symposium will discuss recent advances in understanding both the metabolism and function of membrane lipids, in particular 1) transcriptional regulation of genes involved in lipid metabolism, especially sterols and fatty acids; 2) elucidation of the functions of individual membrane lipids; 3) regulation of pathways of lipid biosynthesis, and (4) lipids as signal transducing molecules.

Signaling Molecules in Development
Organizer: N. Perrimon

Keynote Addresses: T. Jessel and P. A. Beachy

In this symposium, recent advances in how various signaling pathways control cell fate decisions and patterning will be presented. Specifically, signaling pathways that implicate molecules such as Hedgehog, Wnt, Notch, and Eph will be discussed. The use of model systems to identify molecules involved in specific signaling pathways, as well as to elucidate the biological functions of some of these pathways will be emphasized.

Specificity of Signal Transduction Events by Targeting and Anchoring
Organizers: A. Newton and J.D. Scott

Keynote Address: A.J. Pawson

Correct localization of signal transduction enzymes with their substrates is a key determinant in ensuring specificity in cellular signaling. This meeting will focus on how nature ensures that the right enzymes are in the right place at the right time, i.e., key advances in understanding how macromolecular interactions regulate signal transduction. Emphasis will be placed on recent advances in the study of enzyme targeting mechanisms and in presenting newly emerging scaffolding, anchoring or adapter proteins that provide platforms for enzyme targeting. Session one will target the molecular mechanisms of how modules are used to reversibly target proteins to membranes. Session two will concentrate on targeting mechanisms for two key signal transducers: kinases and phosphatases. Session three will address the structural basis for specificity, emphasizing how molecular determinants dictate protein:protein recognition. Session four will be devoted to how proteins are directed in and out of the nucleus.

Molecular Structure and Function in Drug Discovery and Design
Organizer: G. Johnson

Keynote Address: J. Broach

The bridge between basic biomedical research and drug discovery is accelerating rapidly. Many new technologies have been developed for use in high throughput screening, including the expression of human genes in model systems such as yeast and frog melanocytes. Also, highly sensitive reporter systems involving luminescence and fluorescence have made miniaturization of reporter systems possible, so that screening for novel compounds that alter the activity of the target protein can be done on a microchip. Combined with a revolution in combinatorial chemistry and differential display techniques, the ability to discover new lead compounds for therapeutic uses is accelerating quickly. The human genome project and defining disease genes adds to the excitement of drug discovery for the next decade. Participants will present recent advances in screening technologies and show how structural determination of receptors and enzymes can lead to the rational design of potent biologically active small molecule agonists and antagonists.

	Special Sessions

TOP INTRODUCTION Symposia Biochemical Education Symposia Satellite Sessions Special Sessions

 
Public Affairs
Peer Review 101: How an NIH Study Section Operates
Chair: H.K. Schachman

Present and Future of Biomolecular Mass Spectrometry
Cochairs: R.L. Niece and G. Siuzdak

Mass spectrometry is fast becoming an integral part of biological research mainly due to the development of two ionization techniques: matrix-assisted laser desorption/ionization (MALDI) and electrospray ionization (ESI). Both MALDI and ESI have greatly advanced our ability to characterize large, thermally labile molecules by mass spectrometry. They provide an efficient means of generating intact, gas phase ions and have significantly extended the applicability of mass spectrometry to a wide variety of biologically relevant compounds including peptides, proteins, carbohydrates, and oligonucleotides. Most significantly, MALDI and ESI have been used to gain important molecular weight information on biological samples with unprecedented speed, accuracy, and sensitivity. Recent developments in instrumentation and new sampling methods have not only allowed for these higher levels of sensitivity, increased mass range, and better mass accuracy, but also have led to an increasing number of mass spectrometry-based applications to the study of both the covalent and noncovalent structure of biopolymers. Here we will describe these technological advances and discuss their implications for biochemical research. This symposium will provide the potential user of mass spectrometry with a background on the kind of information this technology offers and how to prepare samples for mass spectrometry. A range of current and future applications of mass spectrometry to biochemical and molecular biology will be presented.

1998 Excellence in Science Lecture
The FASEB Board of Directors has approved the nomination of Eva J. Neer, M.D., for the 1998 Excellence in Science Award. Dr. Neer is a Professor of Medicine at Harvard Medical School and Senior Biochemist, Brigham and Women's Hospital.

Dr. Neer, who is a member of ASBMB, was nominated "in recognition of her pioneering contributions to the knowledge of cellular signal transduction mechanism, and of her leadership as mentor and educator in the biochemical and biomedical sciences."

She will present her lecture, "From Modified Molecules to Modified Mice: New Insights into Heterotrimeric G Protein Function," at ASBMB's annual meeting on Tuesday, May 19 at 8:30 a.m. See the Program for further details.

All women who are members of one or more of the FASEB Member Societies are eligible for the annual award, which is sponsored by Eli Lilly and Company.

View larger version (129K): [in this window] [in a new window]   Figure . Eva J. Neer

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