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Albany 2013: Conversation 18

category image Albany 2013
Conversation 18
June 11-15 2013
©Adenine Press (2012)

Topics, Speakers, Chairs and Guests

The 18th Conversation, June 11-15, 2013 will be held at the State University of New York, Albany, NY 12222 USA. Participants will arrive on Tuesday June 11th, there is a reception that evening. The scientific program starts Wednesday morning June 12th and will end after lunch on Saturday June 15th at 2:00 PM. The conference will have roughly 50 lectures by leading scientists, in addition to several short lectures by young scientists who will be selected from abstracts submitted for poster presentations. We will have on display, throughout the conference, some 250 posters. We anticipate about 400 participants with diverse background from over 20 countries for these continuing conversations.

Young Scientists Lecture Program
The Organizing Committee has left 5.5 hrs of the Conversation time for the young scientists lecture program. Extraordinarily talented young professional researchers, at the rank of assistant professors, post-doctoral fellows and doctoral students, will be selected from the abstracts submitted for lecture + poster presentations to provide oral presentations which will be sandwiched between those by senior scientists. Go to link below.

Director
Ramaswamy H. Sarma, Department of Chemistry
State University of New York, Albany NY 12222 USA
ph: 518-456-9362; fx: 518-452-4955; email:rhs07@albany.edu

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Detailed Daily Program of Speakers and Events
After Deadline Unscheduled Abstracts & Posters
Abstracts: Requirements & Deadlines
Registration, Meals and Accommodation
Young Scientists Speaker Program
Financial Assistance
Albany 2013: The 18th Conversation Poster
Albany 2013: Book of Abstracts



Sponsored by:
University at Albany (pending)

    Department of Chemistry
    Department of Biology
    Office of the Dean, Arts and Sciences
    Office of the Vice President for Research
National Institutes of Health (pending)
JBSD and
Adenine Press



Keynote Address- Origin of Life and Evolution
The Albany Conversation traditionally holds evening lectures in areas of fundamental interest to structural biology. In 2013, on Wednesday June 12th 7:30 PM, Nobel Laureates Ada Yonath and Jack W. Szostak will provide back to back keynote lectures on the chemistry of the origin of life. Ada Yonath from the Weizmann Institute of Science, Israel, demonstrates that the universal cellular machines, the ribosomes, possess spectacular architecture accompanied by inherent mobility, allowing for their smooth performance as polymerases that translate the genetic code into proteins. The site for peptide bond formation is located within a universal internal symmetrical region. The high conservation of this region implies its existence irrespective of environmental conditions and indicates that it may represent an ancient RNA machine. It is the thesis of Jack Szostak, Harvard Medical School, that primitive cells may have consisted of a cell membrane and an encapsulated RNA genome, with the replication of both components driven by chemical and physical fluctuations in the environment. Understanding the pathways leading to the synthesis and replication of the primordial RNA genome remains a central challenge in origin of life studies. Jack will describe recent experimental progress in the area of non-enzymatic template-directed RNA replication.

Origin of Life and Evolution Continues
George E. Fox, University of Houston, will describe efforts to understand the origins and evolution of the protein synthesis machinery, treating ribosomes as common ancestors, and exploring the transition from the hypothetical RNA World to living systems. Analysis of the central translation machinery by Gustavo Caetano-Anollés, Univ. of Illinois, Urbana, revealed unanticipated views of the history of aminoacyl-tRNA synthetases, tRNA and the ribosome. In these studies, important clues about the origin of the genetic code and the functioning of early cells suggest crucial specificities unfolded gradually by coevolution of emerging proteins and nucleic acids. Phil Holliger, MRC, Cambridge, UK, will discuss progress in the engineering and evolution of improved RNA polymerase ribozymes with the aim of building modern-day “Doppelgangers” of the ancestral replicase to reconstruct and study life’s first genetic system. Irene Ann Chen, Harvard Medical School, seeks to understand the evolution of RNA sequences in the prebiotic world. Sequences evolve by climbing fitness 'peaks' in sequence space. Irene's talk will describe her efforts to delineate a fitness landscape for functional RNA and to understand mutational movement in sequence space without enzymes. Samanta Pino, University of Rome, Italy, ponders on the emergence of pre-genetic information; she proposes the theory that HCN/formamide could have afforded the precursors of the synthetic pathways eventually leading to RNA and to the key components of the central metabolic cycles. She will report on evidence of ribozymic activity of abiotically generated RNA. Linda McGown, RPI, has been studying the unique self-assembly properties of guanosine monophosphate (GMP) in the context of an RNA world on prebiotic Earth. Here she goes a step further to investigate the reversible phases formed by mixtures of GMP with each of the other RNA nucleotides (XMP). Linda's hypothesis is that the competition between reversible aggregation and covalent, abiotic polymerization directed RNA toward sequences that were best suited to life on early earth.  Günter Wächtershäuser, a German chemist turned patent lawyer, dwells on the possibility of metabolic reproduction by products promoting their own synthesis, and of metabolic evolution by products promoting the synthesis of others. Thus, early evolution occurs by high-probability feed-back and feed-forward ligand effects as an avalanche of concatenated metabolic self-expansions — a unique, complexity-increasing, directional process, pre-ordained in the universal laws of chemistry and definitely knowable. Primordial catalysts, the Urzymes, derived from the invariant cores of enzyme superfamilies, is the subject of discussion by Charlie Carter, Univ of North Carolina at Chapel Hill. Zakharia Frenkel University of Haifa, Israel, uses the text segmentation approach to reveal simple repeat "fossils" in genomic sequences. Sudha Rajamani, IISER, Pune, India, will present her studies on the synthesis of informational polymers by guided polymerization reactions in liquid crystalline matrices of lipids. Amphiphilic lipids spontaneously self-assemble to form orderly structures that concentrate reactants yet also permit diffusional mobility. Under prebiotically relevant conditions, monomers form highly ordered 2-dimensional films in these micro environments, thereby overcoming entropic barriers. These conditions also produce a chemical potential that reduces water activity. This shifts reaction equilibrium towards condensation thus promoting the formation of complex mixtures of oligomers under prebiotic conditions.

RNA and the complexities
Paul Schimmel, Scripps, dwells on new biology from ancient enzymes. The aminoacyl tRNA synthetases arose early in evolution to establish the genetic code during translation. Long thought of as cytoplasmic enzymes with a single defined function, an increasing number of studies have demonstrated their roles in nuclear and extracellular signaling pathways, where they regulate angiogenesis, inflammation, mTor signaling, tumorigenesis, and more. These novel functions are typically associated with novel domains added to higher eukaryote tRNA synthetases, and specific resected forms that are generated by alternative splicing and natural proteolysis. Shulamit Michaeli, Bar-Ilan Univ., Israel, will talk about the spliced leader RNA  silencing  pathway and regulation by non-coding RNAs; Trypanosoma brucei is the causative agent of African sleeping sickness. The parasite cycles between its insect (procyclic form) and mammalian hosts (bloodstream form). Trypanosomes lack conventional transcription regulation, and their genes are transcribed in polycistronic units that are processed by trans-splicing and polyadenylation. In trans-splicing, which is essential for processing of each mRNA, an exon, the spliced leader (SL) is added to all mRNAs from a small RNA, the SL RNA. Trypanosomes lack the machinery for the unfolded protein response (UPR), which in other eukaryotes is induced under endoplasmic reticulum (ER) stress. Trypanosomes respond to such stress by changing the stability of mRNAs, which are essential for coping with the stress. However, under severe ER stress that is induced by blocking translocation of proteins to the ER, treatment of cells with chemicals that induce misfolding in the ER, or extreme pH, trypanosomes elicit the spliced leader silencing (SLS) pathway. In SLS, the transcription of the SL RNA gene is extinguished, and tSNAP42, a specific SL RNA transcription factor, fails to bind to its cognate promoter. SLS leads to complete shut-off of trans-splicing.   Shula has recently revealed the mechanism of SLS and this will be described in her talk. Joachim Frank at Columbia Univ. has solved the structure of the T. brucei ribosome, using cryo-EM, homology modeling, ab initio modeling of several RNA expansion segments and protein extensions unique to Trypanosomes, and molecular dynamics flexible fitting.  Ribosomes from T. brucei and T. cruzi, studied earlier at lower resolution, share an unusual architecture distinct from that of other eukaryotes, characterized by very large RNA expansion segments and a unique processing of the large ribosomal subunit's rRNA into six pieces. The function of these specific features remains unclear but they are presumably linked to the need to adapt protein synthesis very rapidly to the alternating hosts. While much is known about the ribosome, there is much less known regarding ribosome assembly and how assembly impacts the functional capacity of ribosomes. The long-term goal of Gloria Culver, Univ. of Rochester, is to gain a detailed understanding of ribosome biogenesis in bacteria and thus reveal the impact of this dynamic process on fundamental aspects of cell physiology, such as growth regulation and antibiotic action. Pre-mRNA splicing of RNA polymerase II transcripts is executed in the cell nucleus within a huge (21 MDa) and highly dynamic RNP machine – the supraspliceosome. Supraspliceosomes also harbor other components of pre-mRNA processing, such as the RNA editing enzymes ADAR1 and ADAR2, cap-binding proteins, and 3'-end processing components. The structure of the native spliceosome, at a resolution of 20 Å, was determined by cryo-EM, and Ruth Sperling, Hebrew University of Jerusalem, will discuss a model, which is based on computational studies of the localization of spliceosomal sub-complexes of known structures within the native spliceosome, with respect to splicing and alternative splicing.

Exciting Developments
Molecular dynamics (MD) simulation has long been recognized as a potentially powerful tool for understanding the structural, dynamic, and functional characteristics of proteins at an atomic level of detail. Many biologically important phenomena, however, occur over timescales that have previously fallen far outside the reach of MD technology. David Shaw of Shaw Research and Columbia Univ. has constructed a specialized, massively parallel machine, called Anton, that is capable of performing all-atom simulations of proteins in an explicitly represented solvent environment at a speed roughly two orders of magnitude beyond that of the previous state of the art. Using novel algorithms developed within his lab, the machine has now simulated the behavior of a number of proteins for periods as long as two milliseconds -- approximately 200 times the length of the longest such simulation previously published. Such simulations have allowed to observe and analyze key characteristics of the dynamics of proteins (including central elements of the process of protein folding) that were previously inaccessible to both computational and experimental study. Frank Alber, Univ. of Southern California, presents an approach for the comprehensive integration of varied experimental data to study the spatial organization of genome architectures. To address the challenge of modeling highly variable genome structures, he introduces a population-based modeling approach and interprets the result in terms of probabilities of a sample drawn from a population of heterogeneous structures. Knowing the spatial probability distributions of individual genes provides insights into gene regulatory and replication processes, and also allows studying the basic principles of genome structure organization. David Deamer , Univ. of California, Santa Cruz, has carried out field studies in hydrothermal environments associated with volcanic activity in Kamchatka, Iceland, Hawaii and northern California. By understanding the complexity of these early Earth analogue  environments, he has constructed a laboratory simulation of prebiotic conditions. When mixtures of amphiphilic compounds and  mononucleotides are exposed to such conditions, a self-assembled multilamellar matrix of the amphiphiles promotes polymerization of the monomers into RNA-like molecules. Deamer will describe how single molecule nanopore analysis can be used to detect synthesis of the polymers.  Dima Kozakov, Boston Univ., addresses the mechanism of DNA denaturation by formaldehyde  with the aid of a computational mapping method, analogous to X-ray and nuclear magnetic resonance techniques for observing weakly specific interactions of small organic compounds with a macromolecule in order to establish important functional sites.  His results show that in B-DNA, cytosine amino groups are totally inaccessible for the formaldehyde attack, at the same time Hoogsteen (HG) base pair formation dramatically affects the accessibility for formaldehyde of cytosine amino nitrogens within WC base pairs adjacent to HG base pairs. The obtained data emphasize the significance of DNA HG breathing for formaldehyde reaction with DNA.

Enzyme Dynamics
In eukaryotes, cytosolic chaperonin CCT is essential for the correct and efficient folding of many cytosolic proteins, most notably actin and tubulin.  Structural studies of CCT have been hindered by the failure of standard crystallographic analysis to resolve its eight different, yet highly similar, subunits at low resolutions.  Here Michael Levitt, Stanford Univ., exhaustively assesses the fit of all possible CCT models to available crystallographic data with resolution of 3.8 Å.  This unbiased analysis, which relies solely on the side-chain signal of Levitt's models, finds the native subunit arrangement with overwhelming significance.  The resulting structures reveal that the CCT particle is clearly partitioned into an ATP-hydrolyzing side that is opposite to the substrate-binding side.  The successful retrieval of the strong side-chain signal at such resolutions indicates that similar statistical approaches could greatly expand the scope of low-resolution crystallography. The talk by Arieh Warshel, Univ. of Southern California, will start by establishing the meaning of the dynamical events in a unique logical way . Then advanced simulation approaches will be used, including modeling the coupling between catalysis and conformational changes in millisecond processes , to establish that dynamic effects cannot influence the rate of the chemical steps , unless one deals with ultrafast light induced reactions. The same analysis will then be applied to allosteric transitions and to the control of replication fidelity , reaching similar conclusions and showing that checkpoints and related concepts cannot influence the fidelity unless the conformational changes are rate limiting. In addition to the conceptual part of the talk, powerful demonstrations of Warshel's ability to actually predict and quantify catalytic effect and to explore different catalytic and functional proposals, will be provided. This will be done for both enzymatic processes and molecular motors that use chemical energy.

Protein Protein Interactions
Using a newly developed algorithm (PrePPI – Predicting Protein-Protein Interactions) Barry Honig, Columbia Univ., shows that three-dimensional structural information can be used to predict protein-protein interactions with an accuracy and coverage that are of comparable quality to high-throughput experiments. The surprising effectiveness of three-dimensional structural information can be attributed to the use of homology models combined with the exploitation of both close and remote geometric relationships between proteins. The results suggest that Structural Biology and molecular Systems Biology can be integrated at an extent that has not been possible in the past. Impact of cancer mutations on binding properties of proteins and their interaction networks is the subject of lecture by Anna Panchenko of NCBI. Many studies have shown that missense mutations might play an important role in carcinogenesis, however, the extent to which mutations might affect biomolecular interactions remains unclear. Anna presents an endeavor to map cancer mutations on the human protein interactome, model affected protein complexes and decipher the effect of mutations on protein interactions. Under the title "Plucking the High Hanging Fruit", Paramjit Arora, NYU, provides a systematic approach for targeting protein-protein interactions (ppi). Development of specific ligands for protein targets that help decode the complexities of protein-protein interaction networks is a key goal for the field of chemical biology.  Despite the emergence of powerful in silico and experimental high-throughput screening strategies, the discovery of synthetic ligands that selectively modulate protein-protein interactions remains a challenge.  Arora will discuss emerging principles for the rational design of ppi inhibitors. Udo Heinemann, MDC, Berlin, Germany, takes up ATPases which are associated with diverse cellular activities (AAA ATPases) and are hexameric proteins regulated by various adaptor proteins. Udo will provide structural insight into a novel mechanism of AAA ATPase regulation by adaptor-mediated hexamer disassembly.

Proteins: Interactions and Folding
George Rose, Johns Hopkins, takes up protein domains. Protein domains are conspicuous structural units in globular proteins, and their identification has been a topic of intense biochemical interest dating back to the earliest crystal structures.  Numerous disparate domain identification algorithms have been proposed, all involving some combination of visual intuition and/or structure-based decomposition.  Instead, George presents a rigorous thermodynamically-based approach that redefines domains as cooperative chain segments. Arieh Ben-Naim, The Hebrew Univ. of Jerusalem, Israel, claims that analysis of all the possible solvent induced contributions to the thermodynamic driving force for protein folding and protein-protein association reveals that, contrary to the commonly accepted paradigm, hydrophilic interactions might be more important than hydrophobic interactions. Arieh will present examples of hydrophilic interactions on solubility of proteins, protein folding, protein-protein association and molecular recognition. Robert Jernigan, Iowa State Univ., discusses extorting Dynamics Information from Multiple Structures. There is significant information that can be extracted from multiple experimental structures of the same, or closely related, protein or RNA. This dynamics information provides strong evidence for the plasticity of protein and RNA structures, and also suggests that these structures have a limited repertoire of motions. Some mutants exhibit normal dynamics and others show significantly perturbed dynamics. Shoshana Wodak, Hospital for Sick Children, Toronto, Canada, takes up backbone flexibility and new protein function. Local backbone flexibility along the chain was analyzed in pairs of monomer and homodimeric protein structures with identical sequence. Pairs where highly flexible regions (corresponding to prominent peaks in rmsd’s or crystallographic B-factor values) clearly ‘migrate’ to a new location along the polypeptide in the homodimer were identified. Several cases are presented where the new flexible region can be linked to the recruitment of a 3rd binding partner, and where this recruitment is not reported for the corresponding monomer. Conformational sampling of these systems over microsecond timescales further confirms the flexibility migration phenomenon. Compelling evidence is provided that altered backbone flexibility in the homodimer state enables specific recruitment of the heterologous binding partner through the process of conformational selection.

Intrinsically Disordered Proteins
Igor Lednev, University at Albany, will probe amyloid fibril polymorphism by advanced vibrational spectroscopy. Despite a significant biological and biomedical importance, the nature of the amyloid fibril polymorphism remains elusive. Igor's lab has utilized for the first time three most advanced vibrational techniques to probe the core, the surface and supramolecular chirality of fibril polymorphs.  Spontaneous refolding from one polymorph to another was discovered.Liz Rhoades, Yale Univ., attempts to define structure in disordered proteins. Intrinsically disordered proteins are involved in a range of functional roles in the cell, as well as being associated with a number of diverse diseases, including cancers, neurodegenerative disorders, and cardiac myopathies.  Single molecule fluorescence approaches have been used to characterize disordered proteins implicated in the progression of Parkinson's and Alzheimer's diseases. The goal is to understand how disease-associated modifications to these proteins alter their conformational and dynamic properties and to relate these changes to disease pathology. Vinod Subramaniam, University of Twente, The Netherlands, will provide nanoscale quantitative insights into alpha-synuclein amyloid oligomer structure, composition, and membrane interactions. Misfolding and aggregation of proteins into nanometer-scale fibrillar assemblies is a hallmark of many neurodegenerative diseases. A particularly relevant question is the role of early oligomeric aggregates in modulating the dynamics of protein nucleation and aggregation. The transient nature, inherent heterogeneity, and low numbers of early stage aggregates necessitate single molecule spectroscopy approaches that can detect distributions of structures in ensembles. The author has worked extensively on the conformational dynamics and self-assembly of the human intrinsically disordered protein alpha-synuclein, involved in the etiology of Parkinson’s disease. In this research talk, he presents single molecule fluorescence approaches to gain insights into the structure and composition of oligomeric aggregates of alpha-synuclein. Complementary fluorescence correlation, tryptophan fluorescence, and electron paramagnetic resonance spectroscopy experiments yield further insights into the interactions of these oligomeric species with lipid membranes.Sara Bondos, Texas A & M Health Science Center, will talk on generating context-specific functions with intrinsically disordered domains. Many transcription factors that direct animal development instigate different developmental pathways – and thus regulate different genes - in each tissue in which they are expressed.  For the Drosophila Hox transcription factor Ultrabithorax, interactions between the structured DNA binding homeodomain and large intrinsically disordered regions i) create DNA binding specificity ii) provide mechanisms to modulate this specificity in response to tissue-specific cues, and ultimately iii) coordinate DNA binding with other protein functions. Antonio del Sol, University of Luxembourg. The Luxembourg Centre for Systems Biomedicine (LCSB) in collaboration with the Systems Biology Institute in Tokyo (SBI) have developed a Parkinson's disease (PD) map composed of molecular networks made up of genes, proteins and small molecule reactions related to PD pathologies. Further, del Sol's group at the LCSB has analyzed such a map by using graph theoretical approaches to obtain a system level understanding of genotype-phenotype relationships- to identify key components in the disease regulation and to generate experimentally testable hypotheses for PD susceptibility and progression. These hypotheses will be used to design validation experiments and propose new treatment alternatives.

Recent Developments: Virus Structure & Function
Wes Sundquist, University of Utah, takes up ESCRT Pathway in HIV Budding and Cell Division. The Endosomal Sorting Complexes Required for Transport (ESCRT) pathway mediates intraluminal endosomal vesicle formation, budding of HIV-1 and other enveloped viruses, and the final abscission step of cytokinesis in mammals and archaea. The lecture will review the current understanding of the roles of different ESCRT factors in HIV budding and abscission. In particular, Sundquist will describe his experiments aimed at understanding how the filament-forming ESCRT-III subunits and the VPS4 ATPase assemble and function in membrane fission. Nikolai Ulyanov, NIH, will lecture on the conversion of the HIV-1 SL1 RNA dimer from its immature into mature form via the cruciform branch-point migration. A specialized nucleic acids modeling software, miniCarlo, is used to investigate structural transitions during maturation of the dimeric genomic RNA of HIV-1. The initial metastable dimer is established via interactions between the palindromic apical loops of stem-loop 1 of the 5’-untranslated region RNA; this dimer is then converted into a more stable extended form by the nucleocapsid protein. An atomic-resolution model will be presented for the conversion pathway via the migration of the cruciform branch-point formed between the homologous stems. Inhibiting the transactivation activity of Tat protein has long been proposed as a very attractive strategy to combat the emergence of HIV from latency and overcome resistance to current treatment, but molecules with sufficient potency and specificity to warrant pharmaceutical development have so far not been discovered. Gabriele Varani , University of Washington, will describe picomolar RNA-binding peptide mimetics that inhibit viral replication with activity comparable to current antivirals without cytotoxicity and efficient cell penetration. These lead structures specifically inhibit TAR-dependent reverse transcription as well as activation of transcription and repress replication of a wide variety of viral strains representing all the major HIV clades in primary human lymphocytes. Avi Minsky, Weizmann Institute, Israel, will present structural studies of the infection cycle of giant viruses. With a diameter of ~750 nm and a DNA genome of 1.2M base pairs, the recently discovered virus Mimivirus is the largest virus heretofore identified, blurring the established division between viruses and cellular organisms. These unusual parameters raise fundamental questions concerning the mechanisms that mediate entry of the huge Mimivirus genome into the host cell, virion assembly and genome packaging. The studies presented by Avi elucidate these transactions and indicate that they are exquisitely coordinated in time and space, thus providing an exciting case study in self-assembly. The talk by Dan Fabris, University at Albany, will describe how high-resolution mass spectrometry (MS) can be utilized in combination with structural probing to investigate the 3D structure of ribonucleoproteins both in vitro and in virions. It will also show how ion mobility spectrometry (IMS) could be used not only to investigate RNA structure/dynamics, but also to elucidate the effects of cognate proteins and small molecule ligands, which could be extremely helpful in drug discovery applications.

DNA-Protein Recognition
Richard Mann, Columbia Univ., attempts to understand transcription factor specificities in the context of animal development and he uses the fruit fly, Drosophila melanogaster, to understand transcriptional regulatory mechanisms in an in vivo context. Mann will discuss recent findings from his lab that provide new insights into how transcriptional cis-regulatory modules are spatially and temporally integrated into animal development. One topic will be how transcription factor specificities are generated, a second will be how transcription factor cascades are used in developmental pathways. Zhiping Weng, Univ. of Mass., will lecture on computational analysis of transcriptional regulation in the human genome. This will involve analysis of the ENCODE consortium to reveal the sequence and chromatin features of the regulatory regions in the human genome. While the lecture by Tali Haran, Technion, Israel, will center around super-transactivation sequences and gene regulation by p53, Yael Mandel-Gutfreund, again from the Technion, will delineate novel geometric approaches to uniquely characterize DNA binding interfaces. DNA binding proteins interact with DNA via distinct regions on their surface that are characterized by an ensemble of chemical, physical and geometrical properties. Novel geometry based approaches are presented to characterize and predict DNA surfaces on proteins. These approaches are successfully employed to distinguish DNA from RNA and protein binding interfaces in proteins which share similar folds. Barry Stoddard'slaboratory at Fred Hutchinson Cancer Research Center studies the structure, function and mechanism of homing endonucleases, rare-cutting endonucleases and gene targeting proteins such as TAL effectors. This talk will summarize the current state of the art in understanding the physical basis for DNA targeting and activity by LAGLIDADG homing endonucleases (also termed 'meganucleases') and TAL effectors, and the development of methods to retarget the specificity of those proteins for genome engineering and correction in a variety of applications.

Nanopores
Meni Wanunu, Northeastern Univ., will focus on the use of nanopores to probe nucleic acid structure, as well as to monitor DNA-processing enzyme kinetics using microscopy and nanopore measurements. Alexander Grosberg, NYU, will lecture on electrohydrodynamics of DNA capture into the pore and electric field driven translocation. When DNA is driven by the electric field, the field is undoubtedly strongest inside the pore, but it exists also outside the pore. Importantly, it is long ranged and not subject to Debye screening. These two facts have far reaching consequences.  The talk will explore the delicate interplay between electric and hydrodynamics forces as DNA approaches the pore, inserts its end into the pore, and then crawls. Murugappan Muthukumar, Univ. of Mass., dwells on the theory of DNA transport through protein channels and nanopores. How does DNA worms through protein channels and solid-state nanopores under an external electric field with the aid of polymer theory and modeling? The ubiquitous phenomenon of polymer translocation involves the polymer crossing a conformational  entropic barrier which is further modulated by protein-DNA interactions. The lecture will address the entropic barrier mechanism of polymer translocation by including polymer dynamics, electrolyte dynamics, hydrodynamics, and the confinement effects from the charge-decorated pores. Hagan Bayley, Univ. of Oxford, UK, will talk about single-molecule sequencing with protein nanopores. Single-molecule nucleic sequencing by nanopore technology is an emerging approach for ultrarapid genomics. Strand sequencing with engineered protein nanopores is a viable technology, which has required advances in four areas: nucleic acid threading, nucleobase identification, controlled strand translocation, and nanopore arrays. The latter remain a pressing need, and attempts to improve large arrays will be described. Liviu Movileanu, Syracuse Univ., will address the design of stiff protein nanopores for challenging tasks in biosensing. He will dwell on strategies for coupling protein engineering with refolding approaches to enhance the robustness of protein nanopores, which can be employed under harsh experimental circumstances. This methodology is relied upon native beta-barrel scaffolds present in the outer membranes of Gram-negative bacteria. Examples, pertinent to single-molecule protein detection and aptamer selection, will be discussed.

Ned Seeman's DNA Nanotechnology
As has been the tradition Ned Seeman, New York University, introduces and chairs the session on DNA nanotechnology. Paul Paukstelis, Univ. of Maryland, focuses on non-canonical base pairing motifs in DNA crystal design. Paul and his associates have demonstrated that two related homo-parallel base pairing motifs can be used to rationally design several DNA crystals with unique features. Highly porous crystals with solvent filled channels can be used to encapsulate protein enzymes to create biodegradable solid-state catalysts, while other crystals can function as adaptive biomaterials that change unit cell dimensions in response to pH. Their work also looks to expand the DNA construction kit by identifying new predictable non-canonical base pairing motifs. Hiroshi Sugiyama, Kyoto Univ., Japan, lectures on direct observation of single molecular event in DNA origami frame. Hiroshi and associates designed a DNA frame using DNA origami method, and directly observed the real-time behavior of DNA modifying enzymes by high-speed AFM. This is a  different imaging technique from the indirect fluorescence microscope-based single molecule analysis. Using DNA frame they can observe enzymatic reaction, chemical reactions, and DNA structural changes. Yan Liu, Arizona State Univ., will lecture on DNA nano-architectures for photonic applications.First Yan will describe a general strategy to achieve QD-DNA conjugation for DNA directed assembly with QD emissions from UV-vis to IR. Then she will report their new results in deterministic positioning of 20 and 30 nm AuNPs on DNA origami and their plasmonic interactions with fluorescent dyes. Tim Liedl, Ludwig Maximilians Univ., München, Germany, elaborates on sculpting light with DNA origami. Tim and coworkers used the DNA origami method for the fabrication of self-assembled nanoscopic material that has strong optical activity in the visible range. As a collective optical response emerging from nanostructures in solution, they detect pronounced circular dichroism originating from the plasmon-plasmon interactions in helices consisting of metal nanoparticles. Their results demonstrate the potential of DNA origami for assembly of plasmonic metafluids with optical properties defined by design. The background of the photograph on the left is an artistic rendering by David Goodsell of a 3-D crystal self-assembled in Ned Seeman's laboratory at New York University.

Genome Weak Links
Sergei Mirkin, Tufts Univ., introduces and chairs the session. Batsheva Kerem, The Hebrew University of Jerusalem, Israel, shows that fork stalling at AT-rich sequences and failure of origin activation lead to chromosomal instability at fragile sites. Perturbed DNA replication in early stages of cancer development induces chromosomal instability preferentially at fragile sites. However, the molecular basis for this instability is unknown. Batsheva and associates took two different approaches to study the basis for instability along fragile sites: 1. Analysis of the replication dynamics along two common fragile sites under normal and replication stress conditions. 2. Analysis of the ability of sequences from the fragile region to induce chromosomal fragility in an ectopic locus. The results of these experiments will be discussed. Susan Lovett, Brandeis Univ, demonstrates that DNA template-switching leads to genetic rearrangements and mutations as a response to replication difficulties. Frequent genetic mutations and rearrangements occur in the context of repetitive DNA sequences. Her work points to the role of strand misalignment during replication as a source for these events. They are using genetics to define the mechanisms of these events and the cellular processes that act to avoid these errors. Karen Vasquez, Univ of Texas, Austin, takes up DNA Structure-induced Genetic Instability in Mammals. DNA can adopt a variety of secondary structures that deviate from the canonical Watson-Crick B-DNA form, and the sequences that have the capacity to adopt such non-canonical structures have been implicated in many important biological processes. It has been found that an endogenous H-DNA-forming sequence from the human c-MYC promoter and a model Z-DNA-forming CpG repeat are mutagenic in human cells and in mice, implicating them in disease and evolution. The current studies are designed to determine the mechanisms of DNA structure-induced genetic instability; the roles of mammalian helicases, polymerases, and repair enzymes in H-DNA and Z-DNA-induced genetic instability will be discussed. Andrés Aguilera, University of Seville, Spain, focuses on Transcription and R-loops in genome instability. Genome instability is a cell pathology characterized by high levels of mutation, recombination or chromosome loss that is commonly associated with cancer and a number of genetic diseases. One key cellular process compromising genome integrity is transcription, which can contribute to genome instability via the formation of R-loops or by collisions with the replication machinery. Deciphering the factors and mechanisms responsible for transcription-associated instability is essential to understand genome dynamics and the molecular basis by which different gene expression steps, from transcription to RNA processing and export, can threaten genome integrity.

Chairs of Sessions
Tom Bishop, Louisiana Tech Univesity
Thomas Cheatham III, Univ. of Utah
Ernesto Di Mauro, Univ. of Rome, Italy






Maxim Frank-Kamenetskii, Boston Univ.
Angel Garcia, RPI
Helen Hansma, Univ. of Calfornia, Santa Barbara





Nick Hud, Georgia Institute of Technology
B. Jayram, IIT, Delhi, India
Prakash Joshi, RPI





Vsevolod Makeev, Vavilov Institute for Genetics, Moscow, Russia
Luis Marky, Univ of Nebraska Medical School
Wilma Olson, Rutgers Univ.





Juan Perez, UPC, Barcelona, Spain
Remo Rohs, Univ. of Southern California
Wolfram Saenger, Free Univ. of Berlin







Zippi Shakked, Weizmann Institute of Science, Rehovot, Israel
Jiri Sponer, IBP, Brno, Czech Republic
Edward Trifonov, Univ. of Haifa, Haifa, Israel





Tom Tullius, Boston Univ.
Vladimir Uversky, Univ. of South Florida
Victor Zhurkin, NIH



Speakers, Chairs and Guests
Abe, Namico, Columbia University
Aguilera, Andrés, Univ. of Seville, Spain
Alber, Frank, Univ. of Southern California
Aldersley, Michael, RPI
Alexandrov, Boian, LANL, Los Alamos
Arakelyan, Valerie, Yerevan State Univ., Armenia
Arora, Paramjit, NYU
Arya, Gaurav, UCSD
Aytenfisu, Asaminew, University of Rochester
Banavali, Nilesh, Wadsworth Labs
Bathaie, Zahra, Tarbiat Modares University, Iran
Bayley, Hagan, Univ. of Oxford, UK
Bellaousov, Stanislav, University of Rochester
Ben-Naim, Arieh, The hebrew Univ. of jerusalem, Israel
Belotserkovskii, Boris, Stanford
Beuning, Penny, Northeastren University
Bilotti, Katharina, Brown University
Bishop, Tom, Louisiana Tech Univ.
Bondos, Sara, Texas A & M Health Science Center
Bozkurt, Ayse Muge, Brown Univ.
Caetano-Anollés, Gustavo., Univ. of Illinois, Urbana
Carpenter, Michael, Univ of Minnesota
Carr, Stephen, Rutherford Appleton Laboratory, Oxon UK
Carter, Charlie., Univ. of North Carolina Medical School
Castor, Katherine, McGill Univ., Montreal, Canada
Cervan, Jiri, Univerzity of Ostrava, Czech Republic
Chandrasekaran, Arun Richard, New York Univ.
Cheatham III, Thomas, Univ. of Utah
Cheong, Vee Vee, Nanyang Technological University, Singapore
Chung, Wan Jun, Nanyang Technological University, Singapore
Chen, Irene, Harvard Medical School
Clauvelin, Nicolas, Rutgers Univ.
Conway, Justin, McGill Univ., Montreal, Canada
Cui, Feng, RIT
Culver, Gloria, Univ. of Rochester
Danilov, Victor, National Academy of Sci., Ukraine
Dantas Machado, Ana Carolina, Uni. of Southern California
Datta, Partha, IISER, Kolkata, India
Deamer, David, Univ. of calfornia, Santa Cruz
Delaney, Sarah, Brown University
Del Sol, Antonio, Univ. of Luxembourg
Di Mauro, Ernesto, Univ. of Rome, Italy
Dror, Iris, Univ. of Southern California & Technion, Israel
Duax, William, Hauptman Woodward MRI
Dupureur, Cynthia, Univ. Missouri St. Louis
Edgell, David, Univ. of Western Ontario, Canada
Edwardson, Tom, McGill Univ., Montreal, Canada
Eisenstein, Miriam, Weizmann
Endutkin, Anton, ICBFM, Novosibirsk, Russia
Engelhart, Aaron, Harvard
Fabris, Dan, Univ. at Albany
Faukstelis, Paul, Univ of Maryland
Fedoseyeva, Viya, IMG RAS, Moscow, Russia
Fedorova, Olga, ICBFM SB RAS, Novosibirsk, Russia
Fleming, Aaron, Univ. of Utah
Foster, Amanda, Carleton University, Canada
Fox, George., Univ. of Houston
Frank, Joachim, Columbia Univ.
Frank-Kamenetskii, Boston Univ.
Frenkel, Zakharia, Univ. of Haifa, Israel
Fu, Yinghan, University of Rochester
Gallego, Isaac, Georgia Tech
Galindo-Murillo, Rodrigo, Univ. of Utah
Garcia, Angel, RPI
Garipova, Margarita, Bashkirian State University, Ulf, Russia
Geng, Chun, Univ. of Maryland, College Park
Ghosh, Debjani, West Bengal Univ. of Technology, Kolkata, India
Ghosh, Soma, IISc, Bangalore, India
Gordan, Raluca, Duke Univ.
Greenblatt, Harry Mark, Weizmann
Grosberg, Alexander, NYU
Hamblin, Graham, McGill Univ., Canada
Hansma, helen, Univ. of Calfornia, Santa Barbara
Haran, Tali, Technion, Israel
Hazra, Saugata, Albert Einstein College of Medicine
Heinemann, Udo, MDC, Berlin, Germany
Holliger, Phil., Univ. of Cambridge, UK
Honig, Barry, Columbia Univ.
Huang, Ji, Brown University
Hud, Nick, Georgia Institute of Technology
Hur, Sun, Harvard Medical School
Ivanov, Alexander, Blokhin Cancer Res. Institute, Moscow, Russia
Jayram, B., IISc, Delhi, India
Jernigan, Robert, Iowa State Univ.
Jobe, Amy, Columbia Univ.
Joshi, Prakash, RPI
Jurecka, Petr, Palacky University, Czech Republic
Kaushal, Simran, Tufts University
Kiran Kumar Mustyala, Osmania University, India
Kerem, Batsheva, The Hebrew University of Jerusalem, Israel
Kompanichenko,Vladimir, RAS, Birobidzhan, Russia
Kontratiev, Maxim, Pushchino, Moscow, Russia
Koulgi, Shruti. CDAC, Pune Univ., India
Kozakov, Dima, Boston Univ.
Kührová, Petra, Palacky Unv. Olomouc, Czech Republic
Larkin, Joseph, Northeastern Univ.
Lazzarovici, Allan, Columbia
Lech, Christopher J, Nanyang Technological University, Singapore
Lednev, Igor, Univ. at Albany
Levitt, Michael, Stanford Univ.
Li, Pan, Univ. at Albany,
Li, Li, Harvard Univ.
Liu, Shu-Qun, Yunnan Univ., Kunming, China
Liu, Yan, Arizona Sate Univ.
Lomzov, Alexandr, ICBFM SB RAS, Novosibirsk, Russia
Lott, Britttany Burton, Univ. of Memphis
Lovett, Susan, Brandeis Univ.
Maglia, Giovanni, Univ. of Leuven, Belgium
Makeev, Vsevolod, Vavilov Institute for Genetics, Moscow, Russia
Mamajanov, Irena, Georgia Tech
Mande-Gutfreund, Yael, Technion, Israel
Mann, Richard, Columbia Univ.
Marky, Luis, Univ of Nebraska Medical School
Mastronardi, Emily, Carleton University, Canada
Maxim Frank-Kamenetskii, Maxim, Boston Univ.
McCauley, Micah, Northeastern University
McConnell, Erin, Carleton University, Canada
McGinty, Ryan, Tufts University
McGuinness, Kenneth, UMDNJ/Rutgers University
McGown, Linda., RPI
Medrano, Vilma, Brown University
Michaeli, Shulamit., Bar-Ilan Univ., Israel
Minsky, Avi, Weizmann Institute of Science, Israel
Miriam Eisenstein, Miriam, Weizmann Institute, Israel
Mirkin, Sergei, Tufts Univ.
Mishra, Deepak Kumar, NIT-Durgapur, India
Mishra, Seema, Univ. of Hyderabad, India
Morii, Takashi, Kyoto University
Morozov, Vladimir, Yerevan Univ., Armenia
Mousavi, M. F., Tarbiat Modares University, Iran
Movileanu, Liviu, Syracuse Univ.
Munikumar, Manne, Venkateswara Univ., India
Murugesapillai, Diva, Northeastern Univ.
Muthukumar, Murugappan, Univ. of Mass.
Norouzi, Davood, IASBS, Zanjan, Iran
Novikova, Olga, University at Albany
Ohayoon, Yoel, New York University
Olmon, Eric, Brown University
Olsen, Ole Hvilsted, Novo Nordisk A/S
Olson, Wilma, Rutgers Univ.
Ostermeir, Katja, Technische Univ. München, Germany
Padhi, Aditya, Iisc, Delhi, India
Panchenko, Anna, NCBI
Paukstelis, Paul, Univ. of Maryland
Pearson, Seth, University at Albany
Peretz, Mosshe, Weizmann Institute, Israel
Perez, Alberto, SUNY at Stony Brook
Perez, Juan, UPC, Barcelona, Spain
Petrov, Anton S, Georgia Tech
Petrov, Valery, RAS, Pushchino, Russia
Pino, Samanta, Univ. of Rome, Italy
Pless, Reynaldo, CACATA-IPN Queretro, Mexico
Popov, Alexander, ICBFM SB RAS, Novosibirsk, Russia
Pradhan, Dibya, Venkateswara Univ., Tirupati, India
Priyadarshini, Vani, Venkateswara Univ., Tirupati, India
Qu, Guosheng, Univ. at Albany
Rajamani, Sudha, Iiser, Pune, India
Ramakrishna Annabhimoju, Osmania University, India
Reiling, Calliste, Univ. of Nebraska, Omaha
Ren, Gang (Gary), LBL, Berkeley
Robbins, Timothy, Univ. of memphis
Rhoades, Liz, Yale Univ.
Rohs, Remo, Univ. of Southern Calfornia
Rojas, Ana, University of Rochester
Rose, George, Johns Hopkins Univ.
Rouzina, Ioulia, Univ. of Minnesota
Rozenberg, Haim, Weizmann Institute, Israel
Saenger, Wolfram, Free Univ. of Berlin
Salsbury Jr, Freddie, Wake Forest University
Sander, Stephanie, University at Buffalo
Sarita Rajender Potlapally, Osmania University, India
Schermerhorn, Kelly, Brown University
Schimmel, Paul., Scripps
Seeman, Ned, NYU
Sengupta, Jatati, CSIR-IICB, Kolkata, India
Sergeeva, Alina, Columbia Univ.
Sha, Rvojie, New York Univ.
Shakked, Zippi, Weizmann Institute of Science, Rehovot, Israel
Sharma, Umang, University at Albany
Shaw, David, Shaw Research and Columba Univ.
Shazman, Shula, Columbia Univ.
Sheng, Jia, Harvard Univ.
Singh, Guatam, Rutgers Univ.
Singh, Poonam, Central Drug Institute, Lucknow, India
Singh, Sanjeev, Alagappa University, India
Slaymaker, Ian, Univ. of Southern California
Sobolev, Vladimir, Weizmann Institute of Science, Israel
Somvanshi, Pallavi, Teri University, India
Soni, Anjali, IIT Delhi, India
Sperling, Ruth, Hebrew Univ. of Jerusalem, Israel
Spasic, Aleksandar, University of Rochester
Sponer, Judit E, Insti of Biophysics, Brno, Czech Republic
Sponer, Jiri, Institute of Biophysics, Brno, Czech Republic
Srivastva, Ashutosh, CCMB, Hyderabad, India
Stiltberg-Liberles, Jessica, Univ. of Wyoming
Stoddard, Barry, Fred Hutchinson Cancer Research Center
Subramanian, Hari, Boston Univ.
Subramaniam, Vinod, Univ. of Twente, The Netherlands
Sugiyama, Hiroshi, Kyoto Univ., Japan
Sundquist, Wes, University of Utah
Szostak, Jack., Harvard Medical School ---- Nobel Laureate
Tajmir-Riahi, H.A., Univ. of Quebec at Trois-Rivieres, Canada
Tarantino, Mary, Brown Univ.
Thakkar, Shraddha, Univ of Arkansas for Medical Sciences
Theimer, Carla, University at Albany
Thomashevski, Alexandr, RAS, Pushchino, Russia
Todolli, Stefjord, Rutgers Univ.
Tomasko, Martin, Institute of Biophysics, Brno, Czech Republic
Trifonov, Edward, Univ. of Haifa, Haifa, Israel
Tullius, Tom, Boston Univ.
Ulyanov, Nikolai, NIH
Uma Vuruputuri, Osmania University, India
Uversky, Vladimir, Univ. of Southern Florida
Varani, Gabriele, Univ. of washington
Vardevanyan, Poghos, Yerevan Sate Univ., Armenia
Vasquez, Karen, Univ. of Texas, Austin
Wächtershäuser, Günter., A Patent Lawer from Germany
Wang, Guliang, Univ. of Texas at Austin
Wang, Yongmei, Univ. of Memphis
Wanunu, Meni, Northeastern Univ.
Warshel, Arieh, Univ. of Southern Calfornia
Weng, Zhiping, Univ. of Mass.
Whitford, Paul, Northeastern Univ.
Williams, Loren, Gergia Tech
Williams, Mark, Northeastern University
Wodak, Shoshana, Hospital for Sick Children, Toronto, Canada
Yakubovskaya, Elena, Stony Brook Univ.
Yamana, Kazushige, Univ. of Hyogo, Japan
Yang, Lin, University of Southern California
Yonath, Ada., Weizmann Institute of Science, Israel ---- Nobel Laureate
Zgarbova, Marie, Palacky Univ., Czech Republic
Zhang, Shenglong, Harvard medical School
Xhang, XiaoJu, University of Rochester
Zhou, Tianyin, Univ. of Southern California
Zhuravlev, Yuri, RAS, Vladivostok, Russia
Zhurkin, Victor, NIH