Day 1 :
Keynote Forum
Lin Li
The University Of Texas At El Paso, USA
Keynote: Electrostatic interactions play key roles on the motions of molecular motors
Time : 09:15-09:55
Biography:
Lin Li completed his PhD at Huazhong University of Science and Technology in 2011. He worked as postdoctoral researcher at Clemson University from 2011 to 2016 and then worked as Research Assistant Professor at Clemson University from 2016 to 2017. Since 2017, he has been working as an Assistant Professor at the University of Texas at El Paso. His research focuses on Computational Biophysics. He has published over 30 peer-reviewed papers and has been serving as editorial board members of many journals. He has been invited to give presentations at many international conferences.
Abstract:
Dynein is an important molecular motor which transports cargos along microtubules in the cell. Dysfunction of dynein leads to many serious diseases. Therefore, many efforts have been contributed to investigating the mechanisms of dynein’s motilities on microtubules. However, the large size of the dynein and microtubule system makes it extremely challenging to study the atomic details of the dynein’s motilities. Several computational approaches are developed and applied to study the dynein at different levels. Our simulations demonstrate that the long-range electrostatic interaction plays several essential roles during dynein’s motion. The electrostatic forces control dynein’s binding position and orientation in each step. The electrostatic binding energy funnel is found at the binding pocket, with the diameter of about 30 angstroms. Meanwhile, strong evidence indicates that the electrostatic binding affinity is also a key factor to determine dynein’s velocity and run length.
Keynote Forum
Jun-ichi Kadokawa
Kagoshima University, Japan
Keynote: Enzymatic preparation of nanostructured supramolecular assemblies from biological macromolecules
Time : 09:55-10:35
Biography:
Jun-ichi Kadokawa received his PhD in 1992. He then joined Yamagata University as a Research Associate. From 1996 to 1997, he worked as a visiting scientist at the Max-Planck-Institute for Polymer Research in Germany. In 1999, he became an Associate Professor at Yamagata University and moved to Tohoku University in 2002. He was appointed as a Professor of Kagoshima University in 2004. His research interests focus on polysaccharide materials. He received the Award for Encouragement of Research in Polymer Science (1997) and the Cellulose Society of Japan Award (2009). He has published more than 200 papers in academic journals.
Abstract:
Biological macromolecules, such as polysaccharide and protein (peptide) exhibit specific in vivo functions in living systems, which are appeared by their controlled primary and higher-order assembled structures. Many kinds of conjugates, which are assembled from such biological macromolecules, are present as vital materials in nature. Therefore, artificial assemblies from biological macromolecules can be expected as new bio-based functional materials, which have a potential for practical applications in biomedical and tissue engineering fields. Polysaccharides are known to form nanostructured higher-order assemblies by non-covalent linkages such as hydrogen bonds. Accordingly, the construction of hierarchically assembled structures, so-called supramolecules, from polysaccharides has attracted much attention to obtain new polysaccharide-based functional materials. For example, amylose, which is a linear polysaccharide linked through a(1g4)-glycosidic linkages and well-known as a component of starch, forms regularly controlled assemblies, that is, inclusion complex and double helix, depending on whether guest compounds are present or not. Amylose with well-defined structure is synthesized by phosphorylase-catalyzed enzymatic polymerization using a-d-glucose 1-phosphate (G-1-P) and a(1g4)-oligoglucan (maltooligosaccharide) as monomer and primer, respectively. As the polymerization is initiated from the non-reducing end of the maltooligosaccharide primer, the enzymatic polymerization can be conducted using primers covalently linked to other polymeric materials (immobilized primers) at the reducing end, giving rise to amylose-grafted bio-based polymeric materials. By means of the property of spontaneously double helix formation from the enzymatically synthesized amylose, the phosphorylase-catalyzed enzymatic polymerization using the immobilized primers produces supramolecular assemblies comprising the double helix cross-linking points. For example, the phosphorylase-catalyzed enzymatic polymerization using the immobilized primers on chitin nanofibers was investigated to produce amylose-grafted chitin nanofiber assemblies. Owing to supramolecular network structure by the double helix cross-linking points, the product formed hydrogels, which were further converted into porous materials with controlled nano- and microstructures by lyophilization.
Keynote Forum
Denis Larrivee
Loyola University Chicago, USA
Keynote: Title: Regulation of global brain states: Orienting oscillatory trajectories
Time : 11:00-11:40
Biography:
Denis Larrivee is a Visiting Scholar at Loyola University Chicago and has held professorships at the Weill Cornell University Medical College in New York City and Purdue University, West Lafayette, Indiana. A former fellow at Yale University's Medical School and Department of Biology he received the Association for Research in Vision and Opthalmology's first place award for studies on photoreceptor degenerative and developmental mechanisms. He is the current editor of a text entitled Brain-Computer Interfacing and Brain Dynamics with InTech Publishing and an editorial board member of the journals Annals of Neurology and Neurological Sciences (USA) and EC Neurology (UK). An International Neuroethics Society Expert he is the author of more than 50 papers and book chapters in such varied venues as the Journal of Cell Biology, Journal of Neuroscience, and Journal of Religion and Mental Health, and IEEE Explore
Abstract:
Autonomy, the hallmark of advanced living systems, depends on how the brain and extended nervous system are self-regulated to accommodate the multiplicity of tasks and temporal sequencing that comprises cognitive operation. Directed to the good of the whole organism, self-regulation reveals both the need for and existence of global brain mechanisms that modulate local neural events and oversee their spatiotemporal organization. Hence, there is an implicit coupling between global and local scales that characterize large-scale, systemic operation, requiring that oversight mechanisms be regionally distributed for local activation. Existing evidence indicates that mediating control depends on a distribution of oscillatory, electropotential activity, that is, brain dynamical elements that exhibit repetitive and cyclical profiling. There is a broad consensus that oscillations detectable in EEG patterns, for example, can be grouped in frequency bands denoting different brain states. Because of their significance for human health, this paper considers underlying processes that activate and disengage such oscillatory mechanisms, and that is, therefore, responsible for modulating these states. Controlling such oscillatory networks globally is thought to be achieved through modulation of their frequency patterning, which may, for example, include synchronization, desynchronization, or cross-frequency coupling. Synchronization entails oscillatory overlap, which is thought to bind together various feature elements in cognitive representations, like those of emotions and sensory events; desynchronization, by contrast, entails oscillatory disengagement. Accordingly, the capacity for selectively engaging and disengaging oscillator activity is key to directing different brain states, that is, to mediating the orientation of bifurcations to different dynamical elements. This paper will explore the roles of two processes likely to be critical to inducing regulatory directionality, neural pulsing and neural noise. The two will be considered in the special case of memory circuits, which will be used here as a general model for achieving global brain regulation.
Keynote Forum
Iftikhar Ahmed
University of Southampton, UK
Keynote: Title: Volatile organic metabolites as a novel, non-invasive diagnostic biomarkers in inflammatory bowel disease
Time : 11:40-12:20
Biography:
Iftikhar Ahmed is a consultant gastroenterologist at University Hospital Southampton NHS Foundation Trust and visiting consultant at East Sussex Hospitals NHS foundation trust Eastbourne He is also an Hon. Senior clinical lecturer at the University of Southampton UK. His research interests include investigating the changes in the smell of faeces and breathe in order to understand the pathophysiological mechanisms of GI disorders and to develop a non-invasive biomarker. Through formal laboratory research, he studied the faecal volatile metabolomics profiles of patients with Liver disease ( NAFLD), IBD and irritable bowel syndrome (IBS) in comparison with healthy individuals, and was awarded the degree of Doctorate of Medicine (MD) by the University of the Bristol in 2012. He has collaborative research experience with international colleagues, presented his work at both national and international conferences, and was awarded travel grants and prizes for the best abstracts and oral presentations on various occasions. He is on the reviewer panel of several national and international journals, including Gut, PLoS One, Journal of Gastrointestinal and Liver Disease
Abstract:
The diagnosis of inflammatory bowel disease (IBD) requires extensive and often invasive investigations including colonoscopy and histology and places a heavy burden, both on healthcare resources, because of the cost, and on the individual, in times of disease-related disability and poor quality of life. Recently, there has been increasing interest in non-invasive biomarkers to diagnose IBD and to monitor the disease activity. There is growing scientific interest in the investigation of volatile metabolites and numbers of studies have focused on the utilization of non-invasive biomarkers in the diagnosis of GI disease. The development of sophisticated analytical techniques has enabled the study and interpretation of changes in the faecal and breath volatile organic metabolites (VOMs) and its correlation with the pathophysiological mechanisms in IBD. VOMs are the chemicals that are the products and intermediates of metabolism and may be altered during the diseases process. Changes in the signature of VOMs could potentially provide diagnostic information about health and disease. Multiple studies have reported the differences in VOM profiles of healthy controls vs. patients with IBD other GI disorders. VOM profiles have been used to segregate patients by disease activity and the type of disease. The correlation of VOMs with microbiota is interesting and supports the hypothesis of gut microbial dysbiosis in the etiology of IBD. This provides an important platform to explore the role of dysbiosis in IBD and other GI disorders pathogenesis and development of novel therapeutic targets. In future, further understanding of faecal VOMs may lead to the development of a rapid and simple point of care diagnosis and monitoring of IBD
Keynote Forum
Vaughn Smider
Scripps Research Institute, USA
Keynote: Title: Cow antibodies: Unusual biology and new opportunities
Time : 12:20-13:00
Biography:
Vaughn Smider received his MD and PhD degrees from Stanford University School of Medicine. He is currently on the faculty of the Scripps Research Institute in the Cell and Molecular Biology Department and is also the Chief Scientific Officer of Sevion Therapeutics. His research focuses on both basic biology and applied technology in the antibody field, including antibody genetics, structure, engineering, and development.
Abstract:
Typical mouse or human antibodies have CDR H3 loop lengths of 10-15 amino acids, which often form a flat binding surface for contact with antigen. In contrast, cows can form CDR H3 regions of over 70 amino acids, which form novel ‘stalk’ and ‘knob’ domains that protrude far from the antibody surface. These antibodies utilize an unusual diversity generating system that alters cysteine positions and disulfide bonding patterns in the knob. The functional importance of this antibody system is illustrated by recent experiments showing that cows, unlike other species, can make a broad and potent neutralizing antibody response to spike antigens of HIV.
- Systems and Synthetic Biology | Biochemistry and Enzymology |Antibody Engineering & Therapeutics | Pharmaceutical Biochemistry | Mass Spectrometry in Proteomics |Computational Systems Biology
Location: Colombard
Session Introduction
Hailong An
Hebei University of Technology, China
Title: Identification of the calcium-dependent gating and targeted-drug discovery of calcium-activated chloride channels
Time : 14:00-14:30
Biography:
Hailong An received his PhD degree in Biophysics in Hebei University of Technology in 2005. After that, he was appointed to the faculty in Institute of Biophysics, Hebei University of Technology. From 2006 to 2008, he worked in Hebei Medical University under supervision by Prof. Hailin Zhang as a postdoc. Awarded by China Scholarship Council, he spent 20 months in Prof. Diomedes E. Logothetis’ Lab as a visiting scholar. He focuses on understanding the structure-function relationship of ion channels, the relationship between ion channels and major diseases and drug screening targeting at ion channels. More than 50 papers have been published in academic journals such as Scientific Reports, Journal of Biological Chemistry, British Journal of Pharmacology etc., and more than 40 papers were included in the SCI (total impact factor: 126.52), the paper was cited more than 200 times.
Abstract:
Calcium-activated chloride channels (CaCCs) play vital roles in a variety of physiological processes. Transmembrane protein 16A (TMEM16A) has been confirmed as the molecular counterpart of CaCCs which greatly pushes the molecular insights of CaCCs forward. However, the detailed mechanism of Ca2+ binding and activating the channel is still obscure. To identify the calcium binding site, the authors presented a computational approach which combined the fragment homology modeling with molecular dynamics simulation. Our data show that the first intracellular loop serves as a Ca2+ binding site including D439, E444, and E447. The experimental results indicate that a novel residue, E447, plays a key role in Ca2+ binding. Compared with WT TMEM16A, E447Y produces a 30-fold increase in EC50 of Ca2+ activation and leads to a 100-fold increase in Ca2+ concentrations that is needed to fully activate the channel. It is well established that TMEM16A is a drug target in many diseases, including cystic fibrosis, hypertension, asthma, and various tumors. Therefore, identifying potent and specific modulators of the TMEM16A channel is crucial. Here, the authors identified two modulators from the traditional Chinese medicine, an activator, Ginsenoside Rb1 (GRb1) which can increase the amplitude and frequency of contractions in an isolated guinea pig ileum assay in vivo and serve as a lead compound for the development of novel drugs for the treatment of diseases caused by TMEM16A dysfunction, an inhibitor, matrine which can dramatically inhibit the growth of lung adenocarcinoma tumors in xenografted mice, and may function as an anti-lung adenocarcinoma drug targeting at TMEM16 channels
Dagmar Heinová
University of Veterinary Medicine and Pharmacy in Košice, Slovak Republic
Title: Bird and mammalian lactate dehydrogenase isoenzymes
Time : 14:30-15:00
Biography:
Dagmar Heinová has completed her PhD at the age of 30 years from the University of Veterinary Medicine in Košice, Slovak Republic. She is an Associate Professor in Biochemistry with the special focus in enzymology. She is a tutor of Clinical Biochemistry at the University and supervisor of students final thesis. In the area of lactate dehydrogenase isoenzymes studies, she published seven papers. She also developed a colorimetric method for determination of pepsin activity which was published and patented
Abstract:
Lactate dehydrogenase (EC 1.1.1.27, LDH) is an enzyme widely distributed in cells of living systems. It is involved in carbohydrate metabolism catalyzing the interconversion of lactate and pyruvate with nicotinamide adenine dinucleotide as coenzyme both in the cytoplasm as well as in mitochondria. LDH exists in several isoenzymatic forms that differs each other in their kinetic characteristics (Km, kcat), physicochemical properties (different net charge), response to the inhibition by substrate (pyruvate), and immunological response. Their different net charge predetermines their different migration rate in the electric field that is used in separating of these enzymes in research as well as in diagnostic practice. Five somatic LDH isoenzymes are detected in serum and tissues of vertebrates with heart, skeletal muscle and liver being the LDH richest organs. A buffer system of the pH values 8.6 to 8.8 is commonly used for the separation of these isoenzymes enabling to distinguish five LDH molecules in mammals. In the case of bird LDHs, the observation of all five isoforms under this pH condition is very difficult as they produce only one rather diffuse enzymatic zone. Isoelectric focusing technique in the pH range of 3 to 9 was shown to be a convenient method for bird LDH isoenzyme separation producing a good and clear resolution of all five LDH fractions in chicken (adult as well as embryonic), turkey, pheasant, and pigeon. Different pI values of LDHs of bird and mammalian origin with the similar catalytic properties probably reflect the different phylogenesis of bird and mammalian LDH molecules.
Mehmet Gokhan Habiboglu
Turkish-German University, Turkey
Title: Glycopeptides by quantum chemistry and artificial intelligence
Time : 15:00-15:30
Biography:
M. Gokhan Habiboglu has his expertise in mathematical and computational modelling of biological systems. He had interest in modelling especially the population dynamics of cell cultures and emergent structures of aromatic amino acids. Recently, he shifted his focus on deep neural networks and combined his knowledge in this area with the quantum chemistry calculations to estimate some quantum properties of carbohydrates.
Abstract:
Glycation destroys or impairs the biological function of peptides and proteins. The bacteria cell wall polymers consist of GlcNAc, which is cross-linked with oligopeptides. While glutamine is a nonessential amino acid that can be derived from glucose, some cancer cells primarily depend on glutamine for their growth, proliferation, and survival. Numerous types of cancer also depend on asparagine for cell proliferation. Thus, glucose and asparagine interactions are at the center of cancer. Moreover, Semliki Forest virus grown in mosquito cells consist of asparagine-linked oligosaccharides. Dengue virus envelope protein (E) consists of two N-linked glyscosylation sites asparagine-67 and asparagine-153. N-linked oligosaccharide side chains on flavivirus E proteins have been associated with viral morphogenesis, infectivity, and tropism. Virologically, ZIKV consists of a single-stranded, positive-sense RNA while the genome encodes three structural proteins including an E protein. Both cryo-electron microscopy and crystallization measurements supported the role of asparagine as a glycosylation site for host cell attachment. Recent studies have shown that ZIKV attacks parts of the adult brain that are central to learning and memory. Furthermore, an observable change in the brain is impaired glucose metabolism within Alzheimer´s disease progression, assessed using positron emission tomography to monitor {18F}-2-deoxy-2-fluoro-glucose uptake within the brain of Alzheimer´s disease patients. The exact molecular mechanism between O-GlcNAc and Aβ remains elusive at the atomic level. Here, we present the structures and energetics of Glc-Asn and GlcNAc-Asn complexes in an aqueous solution medium at the electronic level using quantum chemical calculations linked with artificial intelligence studies. To the best of our knowledge, this study represents the first investigations of aqueous glycopeptides usng quantum chemistry associated with artificial intelligence.
Orkid Coskuner Weber
Turkısh-German University, Turkey
Title: Quantum and statistical mechanical and bioinformatics studies in Alzheimer´s and Parkinson´s diseases
Time : 15:50-16:20
Biography:
Orkid Coskuner-Weber completed her PhD studies in biophysics and physical chemistry at the University of Cologne in Germany. She worked as a postdoctoral scientist at the Johns Hopkins University and then at Stanford University. She was a research assistant professor at George Mason University and an assistant professor at the University of Texas at San Antonio. Currently, she is an assistant professor at the Turkish-German University and took a position in Istanbul for opening the Alzheimer’s and Parkinson’s disease research center. She has been working as a scientist at the National Institute of Standards and Technology, USA, since 2005.
Abstract:
Alzheimer’s and Parkinson’s diseases affect 45 million and 10 million people worldwide. The mechanisms of these severe diseases are currently poorly understood at the atomıic and molecular levels. Intrinsically disordered proteins are at the centers of Alzheimer’s and Parkinson’s diseases. These proteins do not adopt stable structures but possess rapid conformational changes and fast aggregation processes. Thus, measurements of their chemical, physical and biological properties at the monomeric and oligomeric levels face challenges. Furthermore, oxidative stress, mitochondrial dysfunction, and genetics, as well as glucose interactions, affect the mechanism of these two neurodegenerative diseases. We study the molecular mechanisms of Alzheimer’s and Parkinson’s diseases at the atomic and molecular levels. For these purposes, we develop and apply novel quantum and statistical mechanical and bioinformatics tools. We published 30 peer-reviewed research papers and a book chapter about these topics. Here, we will discuss the usefulness of quantum and statistical mechanics and bioinformatics in the studies of complex diseases, such as Alzheimer’s and Parkinson’s diseases.