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February 3-6 Genes And The Environment: New Strategies For Research On Multiple Sclerosis Funded by: Accelerated Cure Project for Multiple Sclerosis Organized By: B. Greenberg, The Johns Hopkins Hospital, A. Mellor, Accelerated Cure Project for Multiple Sclerosis, H. Schmidt, Accelerated Cure Project for Multiple Sclerosis |
| The goal of this meeting was to explore what would be the ideal study for identifying gene-environment interactions involved in MS. Although associations with MS have been identified for a few risk factors such as the HLA-DR2 gene haplotype and cigarette smoke, very little progress has been made in explaining the specific biological role these factors play, and the manner in which risk factors interact in the development of MS. However, there are reasons to hope for faster progress in the coming years. High-throughput technologies such as genomic microarrays and new DNA sequencers are producing data in a much more cost-effective fashion than ever before and enabling new experimental strategies Participants in the meeting were drawn from a wide variety of research areas including MS clinical research, genetics, genomics, environmental toxicology, and epidemiology. |
 G. Weinstock, R. Gunsalus |
March 2-5 Living On Human Beings: Metagenomic Approaches And Challenges Funded by: Cold Spring Harbor Laboratory Corporate Sponsor Program Organized By: G. M. Weinstock, Washington University School of Medicine, E. F. DeLong, Massachusetts Institute of Technology, J. I. Gordon, Washington University School of Medicine |
| Traditional methods of studying microorganisms begin with the isolation of single cells from all those present in a sample, followed by their culture. This introduces the bias that only those organisms that can be cultured can be studied. By contrast, metagenomics is concerned with the characterization of the entire community of microorganisms in a sample. This can be done because new sequencing strategies can sequence gigabases of DNA and bioinformatics strategies can find sequences of interest in these gigabases of sequence. There are projects underway to examine the entire microbiota of environments such as the oceans, soil and air. Most excitingly, metagenoimics offers the possibility of treating the human body as a set of habitats and examining the microbial communities of each habitat, whether the mouth, skin or gut. This meeting was designed to define and suggest solutions to some of the conceptual and experimental challenges that this field faces. |
 R. Zorovic, K. Clapp, M. Bear |
March 9-12 Recent Advances And A Multilevel Analysis From FMRP Biology To Clinical Trials Funded by: NIMH Grant to the University of Illinois Organized By: W. T. Greenough, University of Illinois E. Klann, New York University, E. Berry-Kravis, Rush University Medical Center, P. W. Vanderklish, Scripps Research Institute, K. Clapp, FRAXA Research Foundation |
| Significant advances have been made in several areas of Fragile X research, particularly those that shed new light on underlying mechanisms. The meeting was designed to review these new findings and to encourage new ideas on the basic relationships between FMRP function, the neurobiological origins of symptoms, and potential treatments. In particular, participants discussed: FMRP function and regulation; proteomic and high-specificity FMRP target analyses; alterations in synaptic plasticity, structure, and signaling coupled to mGluR and non-mGluR pathways; mechanistic commonalities between Fragile X and other syndromic forms of mental retardation with autism as an endophenotype; systems level approaches to understanding Fragile X syndrome and autism; and clinical trials. |
 P. Mitra, R. Shrock |
March 16-19 Algebraic Statistics, Machine Learning And Lattice Spin Models Funded by: Clay Mathematics Institute Organized By: P. P. Mitra, Cold Spring Harbor Laboratory, D. A. Ellwood, Clay Mathematics Institute, J. Carlson, Clay Mathematics Institute |
| Recently, there have been exciting advances in the application of ideas and algorithms from commutative algebra and group theory to problems of data analysis and statistics, particularly in computational genomics. However, these ideas are not yet widely known to other communities of theorists who may benefit from these developments. The goal of this workshop was to bring together mathematicians working in algebraic statistics, with researchers in machine learning and statistical physics, for mutual pedagogy and for exploration of new research avenues opened up by the application of algebraic techniques to data. |
 A. Levine, J. Witkowski, C. Harley |
March 30-April 2 How Will We Be Able To Cure Most Cancers? Funded by: OSI Pharmaceuticals, Inc. Organized By: R. Weinberg, Whitehead Institute for Biomedical Research, A. Levine, Institute of Advanced Studies, C. Sawyers, Memorial Sloan-Kettering Cancer Center J. A Witkowski, Banbury Center, Cold Spring Harbor Laboratory |
| We have been carrying out research on cancer for over a century and, since the early 1970s, we havediscovered many of the genetic and biochemical changes that turn a normal cell into a cancer cell. Furthermore, our knowledge of the fundamental biology of cancer is likely to undergo another major increase as genome-based techniques begin to be used on a massive scale to characterize the full set of molecular changes in many tumor types. However, the number of cancers that can at present be cured effectively and efficiently remains small. Why is this? Do cancers vary so much that a treatment specific one patient's cancer may ineffective for another patient? What targets are currently available for drug therapy? What can be done to increase the number? What is the potential for combination therapies? What can be done to improve early detection? May we have to face the fact that many cancers may not be curable? |
 M. Capecchi, M. Rudnicki |
April 6-9 Molecular Mechanisms Modulating Skeletal Muscle Mass & Function Funded by: Privaet Support Organized By: A. Goldberg, Harvard Medical School D. Glass, Novartis Institutes for Biomedical Research |
| While many conferences have focused on the early development of skeletal muscle, the roles of satellite cells or contractile mechanisms, this conference reviewed the mechanisms for muscle homeostasis in the adult animal and human. As anyone who has had limb immobilized will appreciate, the loss of muscle can be rapid and very hard to replace. participants in the meeting considered questions such as: What are the molecular mechanisms that occur in response to increased exercise that result in hypertrophy and/or fiber-type switching, and how does inactivity lead to fiber atrophy? How are protein synthesis, proteolysis, and gene expression altered in skeletal muscle during the wasting (cachexia) induced by cancer, cardiac failure, sepsis and renal failure? How do cytokines and hormones influence the properties of muscle in normal and disease states? |
 sB. Shinn-Cunningham |
April 20-23 Theoretical And Experimental Approaches To Auditory And Visual Attention Funded by: The Swartz Foundation Organized By: J. H. Reynolds, The Salk Institute For Biological Studies J. B. Fritz, University of Maryland H. Cohen, The Swartz Foundation |
| Research in the human and macaque has provided a wealth of information on the neural mechanisms that mediate visual attention. Recent psychoacoustic and neurophysiological studies of attention in the auditory system, and research on interactions of visual and auditory attention, have added considerably to this picture. These studies have found parallels with visual attention mechanisms but have also raised new questions, such as the role of adaptive plastic changes in spectrotemporal receptive field shape during selective attention and the nature of the coordination of attention-driven changes at multiple processing levels from cochlea to cortex. The inherently temporal nature of auditory stimuli has also led to interesting insights into the temporal dynamics of auditory attention. The purpose of this workshop was to bring together experimentalists and theoreticians working in auditory and visual attention for a vibrant discussion of current research. |
 J. Watson, M. Raff |
April 27-30 To What Age Should We Be Expected To Work? Funded by: Oliver Grace Professorship Fund Organized By: T. B. L. Kirkwood, Newcastle University, R. N. Butler, International Longevity Center, M. D. Hurd, Center for the Study of Aging, RAND Corporation J. A Witkowski, Banbury Center, Cold Spring Harbor Laboratory |
| Biomedical research on aging is having an impact on two rather different areas that are not yet closely linked. On the one hand, considerable process has been made in elucidating some of the genetic changes and molecular processes that contribute to aging in experimental organisms such as C. elegans, the fruit fly and mice. These processes can be manipulated, prolonging the lifespan of these organisms. On the other, our lives are being extended through better lifestyles and better healthcare, so that we live longer but, it seems, our maximum life spans are unchanged. Is extending the human life span an achievable or desirable goal? Should we concentrate instead on maintaining the quality of life of the extra years we are gaining now? That is, can we live longer and still be healthy? And how what might be possible through applications of research interact with economic, political and ethical forces? |
 J. Schmahmann, H. Breiter |
May 4-7 The Architectural Logic Of Mammalian CNS Funded by: The William Keck Foundation Organized By: P. P. Mitra, Cold Spring Harbor Laboratory, L. W. Swanson, University of Southern California |
| This meeting was held to assess the progress of the Brain Architecture Project. The goals of the Project are to curate human neuroanatomical connectivity information from the existing literature into a knowledge base, and to build suitable user and web interfaces. To complement these literature curation efforts, and also to help shape the corresponding knowledgebase schemas and geometrical templates for the user interface, it would be of great benefit to have an "outline" version of the connectivity diagram of the mammalian brain, as well as a list of "rules" that the circuitry has been observed to follow. Participants were asked to present their overview of the architectural logic of the Mammalian CNS. These might take the form of circuit diagrams at a coarse level for the full system, more elaborate circuit diagrams for subsystems or substructures that have sufficient generality across species or across brain regions, or specific rules. In contrast with the more familiar morphological approaches to comparative neuroanatomy, the meeting was concerned with the logic of the "highway map." |
 D. Westaway, S. Prusiner, I. Baskakov |
May 11-14 Prion Strains: Origins, Mechanisms And Implications For Disease Funded by: NIAID and the Medical Research Council, United Kingdom Organized By: B. Caughey, NIAID Rocky Mountain Laboratories, C. Weissmann, Scripps Florida, J. Collinge, University College London, C. Soto, University of Texas Medical Branch |
| Multiple distinct strains of naturally occurring sheep scrapie can be passaged in mice. Such strains are classically distinguished by their biological properties: they produce distinct incubation periods and patterns of neuropathology in inbred lines of laboratory mice. Furthermore, strains can be re-isolated in mice after passage in intermediate species with different PrP primary structures. The widely accepted protein-only hypothesis, if correct, must be able to explain how a single polypeptide chain could encode multiple disease phenotypes. Clearly, understanding how a protein-only infectious agent could encode such phenotypic information is of wide biological interest and raises intriguing evolutionary questions. Do other proteins behave in this way? The novel pathogenic mechanisms involved in prion propagation may be of far wider significance and relevant to other neurological and non-neurological illnesses. |
 D. Bar-Sagi |
June 16-17 Identifying Kras-Targeted Therapeutic Approaches For Pancreatic Cancer Funded by: The Lustgarten Foundation Organized By: C. J. Der, University of North Carolina at Chapel Hill, N. Tonks, Cold Spring Harbor Laboratory Additional Organizers K. A. Johnke, The Lustgarten Foundation R. Hruban, Johns Hopkins Medical Institutions |
| KRAS mutations occur in 100% of pancreatic cancers, and this meeting focused on targeting the KRAS oncogene for novel therapeutics for pancreatic cancer treatment. Unfortunately, small GTPases such as Ras are not classically considered "druggable" targets, and earlier anti-Ras approaches have not been successful. Nevertheless, there is no doubt that anti-Ras therapeutics have huge potential in the treatment of pancreatic cancer. Two key uncertainties in such efforts are (1) what technologies will be most suitable for functional screens to identify targets for therapeutic intervention, and (2) what model cell/mouse systems should be utilized to apply these technologies. It is the goal of this meeting to identify the best technologies and systems, so that it will be possible to establish and apply genome-wide screens to identify novel modulators of KRAS-mediated pancreatic cancer growth. |
 S. Tingey, R. Martienssen |
Sept. 8-10 Plant Genetics And Gene Regulation Funded by: Cold Spring Harbor - Pioneer Collaborative Research Program Organized By: R. Martienssen, Cold Spring Harbor Laboratory S. Tingey, DuPont Experimental Station |
 J. Flynn, J. Schwartz |
September 14-17 How Can We Improve Our Brains? Funded by: The Charles A. Dana Foundation Organized By: E. R. Kandel, Columbia University W. T. Dickens, Russell Sage Foundation J. A Witkowski, Banbury Center, Cold Spring Harbor Laboratory |
| It is the hope of every parent that their child will be bright and intelligent. Parents work to help their children's brain work better through providing education and stimulation, and society as a whole makes a tremendous commitment to the education of its young people. Are there data emerging from cognitive neuroscience that such education programs should take into account? Are there learning regimes that might be more effective than those typically found in the classroom? At the other end of life, is the hope of all of us that the normal decline in cognitive skills that accompanies aging will be slow. Might "brain exercises" maintain our brains at a higher level of functioning? Is there evidence that such exercise work? Are there effective pharmacological agents? In short, how can we best use the resources of society to help our brains work better throughout our lives? |
 G. Coruzzi, D. Schachtman |
September 21-24 Nutrient Sensing In Plants: What Can Other Model Organisms Tell Us? Funded by: Cold Spring Harbor Laboratory Corporate Sponsor Program Organized By: D. P. Schachtman, Donald Danforth Plant Science Center, A. M. Jones, University of North Carolina, Chapel Hill |
| Nutrient sensing in response to mineral or carbon deficiency and enrichment is an important area of biological research in multicellular eukaryotes. However, the sensing mechanisms and the components of the signal transduction pathways that connect sensing to response are poorly elucidated. Recent progress has been made using different model organisms, but this is still an emerging and somewhat fragmented field of research. Therefore the aim of this meeting was to gather together experts in the plant field with experts using other model systems, to identify parallels among eukaryotes which will help advance nutrient sensing research across organisms. |
 J. Bertranpetit, B. Weir |
October 6-9 Who Are We?: Kinship, Ancestry And Social Identity Funded by: The Richard Lounsbery Foundation Organized By: A. Chakravarti, Johns Hopkins University School of Medicine, M. Foster, University of Oklahoma, J. A. Witkowski, Banbury Center, Cold Spring Harbor Laboratory |
| On the one hand, genetics provides a description of human beings that reflects their biological ancestry. On the other, cultural norms provide a description (often by self-identification) of social ancestry. These two descriptions need not be, and often are not, the same. However, clinical geneticists identify populations which are likely to be genetically more homogeneous by grouping individuals according to their ethnic characteristics. And in recent years, there has been a proliferation of companies offering DNA-based genealogies, established by examining a set of DNA markers, but discrepancies between ancestry revealed by genetic analysis and assumed by cultural descent may profoundly affect individuals views of themselves. The importance of the relationship between genetic and ethnic identities requires careful, rational and critical review. The advent of ever cheaper, high throughput genomic techniques together with the proliferation of companies offering DNA-based ancestry analysis, highlights the need to begin discussions of this topic. |
 E. Hoffman, S. Takeda |
October 14-17 Oligonucleotide-Directed Splicing: Therapeutic Strategies Funded by: Foundation to Eradicate Duchenne, Cure Duchenne Foundation, AVI, BioPharma, Inc., and Prosensa Organized By: E. P. Hoffman, Children's National Medical Center, A. Krainer, Cold Spring Harbor Laboratory, T. A. Partridge, Children's National Medical Center |
| While research and development of small sequence-specific oligonucleotides as small molecule drugs has been pursued for 25 years, it has been rather disappointing. However, very recent studies have shown that oligonucleotides can be used to modify the splicing patterns of pre-mRNAs in genetic disorders, so as to produce a functional mRNA. Such a strategy that might be widely applicable. In recent years, there have also been advances in nucleotide chemistry that have led to oligonucleotides that retain sequence-specific anti-sense activity, while showing little or no protein binding or associated off-target effects, while other developments have improved intracellular delivery in a larger variety of tissues and cells. In the light of these recent advances, this meeting was held to critically review progress on oligonucleotides as therapeutic agents. The goal was to end the meeting with a clearer understanding of the hurdles that remain in using oligonucleotides as therapeutic agents and to highlight research strategies that are likely to be fruitful. |
 K. Klinger, T. Jessell |
October 19-22-Nov. 2 Taking On New Complexities In SMA Biology Funded by: Spinal Muscular Atrophy Foundation Organized By: T. M. Jessell, Columbia University, C. E. Henderson, Columbia University, C. Joyce, SMA Foundation, M. Winberg, SMA Foundation, K. Chen, SMA Foundation |
| The goal of all those working on human genetic disorders is to develop therapies that will alleviate, if not cure, the symptoms of the disorder. This requires identifying therapeutic targets at different organizational levels and determining how best to reach those targets with current or new tools. To this end, the working sessions of this meeting were organized around three themes: Cellular targets (nerve muscle, glia, and their contacts); Molecular targets (SMN2 and downstream molecules); and Functional targets (SMA phenotypes in models and humans). The expectation was that the meeting would help identify and promote collaborative experiments, as well as stimulate rapid translation of research ideas into therapeutics development and clinical research. |
 R. Kingston, M. Ptashne, A. Bird |
December 7-10 Epigenetics: Mechanisms And Regulation Funded by: Cold Spring Harbor Laboratory Corporate Sponsor Program Organized By: S. Berger, Wistar Institute, R. Shiekhattar, Center for Genomic Regulation, A. Shilatifard, Stowers Institute for Medical Research |
| The term "epigenetics" has been used very loosely, to cover states ranging from dynamic, short-lived chromatin-mediated regulation to long-term alteration of chromatin and other extra-chromosomal proteins in non-replicating cells. Given that "epigenetics" now encompasses such a diversity of phenomena, it was felt that a discussion meeting was needed to reassess what phenomena are epigenetic. Themes of the meeting included: How shall "epigenetics" be defined - narrowly or broadly? What are the phenotypes associated with epigenetics? How are epigenetic states regulated? What are the links between epigenetics and human diseases? What are the understudied areas within epigenetics? |