Day 20 :
- Track 1: Genomics and Bioinformatics, Track 2: Integrative Computational Biology, Track 3: Drug Discovery and Integrative Biology
Location: Valencia B, Melia Valencia
Chair
Jeffrey Zheng
Yunnan University, China
Co-Chair
Dang Duong Bang
Technical University of Denmark, Denmark
Session Introduction
Jeffrey Zheng
Yunnan University, China
Title: Variant maps to identify coding and non-coding DNA sequences of genomes selected from multiple species
Time : 10:25-10:45
Biography:
Jeffrey Zheng has completed his PhD in 1994 from Monash University. He is the Professor and Head at the Department of Information Security, School of Software, Yunnan University from 2004. He has published more than 200 papers in national and international conferences, reputed journals and serving as an Editorial Board Member of Information Acquisition. He is active working on exploring mysteries of coding and non-coding DNA/RNA mechanism to use variant logic construction.
Abstract:
In recent years, many DNA sequencing projects are developed on cells, plants and animals over the world into huge DNA databases. Researchers notice that mammalian genomes encode thousands of large non-coding RNAs (lncRNAs), interact with chromatin regulatory complexes, and are thought to play a role in localizing these complexes to target loci across the genome. It is a challenge target using higher dimensional tools to organize various complex interactive properties as visual maps. In this talk, Variant maps are uesd to provide models and experiment results using visual representation techniques to distinguish multiple species – Salmonella, Caenorhabditis elegans, Arabidopsis, Pan troglodytes and human genomes between coding and non-coding sequences selected. Our model uses probability measurements on the DNA sequences to separate coding and non-coding regions respectively to generate visual patterns to identify different sequences. Sample 2D maps are listed and their characteristics are illustrated under controllable environment. Visual results are analyzed to explore their intrinsic properties on selected multiple species of genome sequences.
Lidia Gardner
The University of Tennessee Health Science Center, USA
Title: Importance of Apolipoproteins in MS
Time : 10:45-11:05
Biography:
Lidia Gardner is an Associate Professor in the Department of Neurology at the University of Tennessee Health Science Center. She leads a research program in Multiple Sclerosis at Memphis Veterans Administration Medical Center. Dr. Gardner has extensive experience in biochemistry and molecular biology, basic and clinical research. She is published in leading biomedical journals. She is currently serving on the Institutional Animal Care and Use Committee. Dr. Gardner received an MBA from the University of Memphis and a Ph.D. from the Russian Academy of Sciences in Cell Biology and completed her postdoctoral studies at the University of Tennessee Health Science Center.
Abstract:
Multiple sclerosis (MS) is a multifaceted disease of the central nervous system. We discovered that progressive MS patients have lower levels of apolipoprotein A-I (ApoA-I) in serum and plasma compared to healthy age-matched controls or relapsing remitting patients. Apolipoproteins play important roles in cholesterol transfer and lipid metabolism in the central nervous system. Our data indicate that ApoA-I levels decline with disease progression. Therefore increasing ApoA-I levels might be beneficial for MS patients. We examined the role of ApoA-I in a mouse model of MS - Experimental Autoimmune Encephalomyelitis (EAE). ApoA-I deficient female mice (C57Bl/6-Tg(ApoA1)1Rub/J) demonstrated a higher incidence and severity of the EAE in comparison to the wild type control mice (C57Bl/6J). EAE was accompanied by an increase in cytokines (INF-gamma, TNF-alpha, TGF-ß, IL-2, IL-23) and T cell differentiation into CD25+/Foxp3+ T cells in these animals. To further investigate the role of ApoA-I in MS, we have treated mice with GW3965, an orally active liver X receptor (LXR) agonist. The LXR form heterodimers with retinoid X receptor (RXR) and are important regulators of lipid metabolism. We found that mice treated with GW3965 had a lower disease incidence, EAE scores and cytokine expression compared to mice with regular EAE. Variation of ApoA-I levels correlated with disease incidence and severity. Our studies indicate that LXR activation resulted in increased ApoA-I production in the liver and in the spinal cord of experimental animals. Further investigation into the mechanisms of ApoA-I formation and disease-associated loss might lead to novel therapies in MS.
Cuong Cao
Queen’s University Belfast, United Kingdom
Title: Metamaterials-based label-free nanosensor for conformation and bioaffinity sensing
Time : 11:20-11:40
Biography:
Cuong Cao is currently a Lecturer in Advanced Micro- and Nanodiagnostics within Institute for Global Food Security, Queen’s University Belfast, UK. His research interest includes exploration and exploitation of multifunctional micro- and nanostructures, plasmonics-based biosensing platforms (SPR, LSPR, SERS), and integrated point-of-care analyses with a particular emphasis on detecting and identifying pathogens, biomarkers, food and environment toxins.
Abstract:
Analysis of molecular interaction and conformational dynamics of biomolecules is of paramount importance in understanding of their vital functions in complex biological systems, disease detection, and new drug development. Plasmonic biosensors based upon surface plasmon resonance and localized surface plasmon resonance (LSPR) have become the predominant workhorse for detecting accumulated biomass caused by molecular binding events. However, unlike surface-enhanced Raman spectroscopy (SERS), the plasmonic biosensors are not suitable tools to interrogate vibrational signatures of conformational transitions required for biomolecules to interact. In this presentation, we demonstrate that plasmonic metamaterials consisting of periodic arrays of artificial split-ring resonators (SRRs) can enable capabilities of both sensing and fingerprinting of biomolecules. By engineering geometry of individual SRRs, LSPR frequency of the metamaterials could be tuned to visible-near infrared regimes such that it allows parallel acquisition of optical transmission and highly SERS spectra from large functionalized SRR arrays. This will provide the basis for the development of a dual detection platformthat can simultaneously probe conformational states and binding affinity of biomolecules, e.g. G-quadruplexes, in different environments. We further present the use of the metamaterials for fingerprinting and detection of arginine-glycine-glycine domain of nucleolin, a cancer biomarker which specifically binds to a G-quadruplex, with the picomolar sensitivity. The dual-mode nanosensor will significantly contribute to unraveling the complexes of the conformational dynamics of biomolecules as well as to improving specificity of biodetection assays.
Bakovic Marica
University of Guelph, Canada
Title: The phospholipid enzyme CTP:phosphoethanolamine cytidylyltransferase (Pcyt2) is a new target for oxidative stress therapy and ischemia
Time : 11:40-12:00
Biography:
Marica Bakovic completed BSc in Chemistry and PhD in Biological Chemistry at the University of Alberta. She received post-doctoral awards from Medical Research Council and Alberta Heritage Foundation. Before coming to the University of Guelph, she worked in the area of molecular and cell biology of lipid metabolism at the Faculty of Medicine, University of Alberta. Currently, she is Professor in the Department of Human Health and Nutritional Sciences at the University of Guelph. Dr. Bakovic has a long-lasting interest in nutrition and metabolism, especially in the area of regulation of membrane phospholipids, fatty acids, and methyl-group donors.
Abstract:
It is well-known that is beneficial to transiently block respiration during ischemia/reperfusion; however there is an unmet clinical need for discovering new compounds and targets that can inhibit the respiration. We established that the ‘over-the-counter’ anti-histaminergic drug Meclizine could inhibit mitochondrial respiration (uncoupling the OXPHOS) by elevating the levels of phosphoethanolamine, an intracellular metabolite in phospholipid biosynthesis and the exclusive substrate of Pcyt2. That phosphoethanolamine was the only elevated intermediate (35-fold) during the inhibition of respiration with Meclizine strongly directed towards Pcyt2 as the drug target. The extensive metabolic studies as well as studies on recombinant Pcyt2 protein provided strong evidence for direct inhibition of Pcyt2 with Meclizine. The impact of our discovery is not only how to expand the future use of Meclizine but also to offer the first inhibitor for the CDP-ethanolamine Kennedy pathway, to continue to investigate the regulation of the membrane phospholipid synthesis and the basic function of Pcyt2. This is the first time to be demonstrated that the membrane biogenesis impacts mitochondrial OXPHOS and that the inhibition of the CDP ethanolamine pathway at the level of Pcyt2 is protective under pathological conditions of oxidative stress and ischemia.
Dang Duong Bang
Technical University of Denmark, Denmark
Title: Towards a total integrated Lab-on-a-chip system for food safety
Time : 12:00-12:20
Biography:
Dang Duong Bang received his MSc (1990) and PhD (1995) in Molecular Biology from Leiden University, Leiden, The Netherlands. Since 1998 he worked as aresearch scientist at National Veterinary Institute and was promoted as senior scientist and leader of Laboratory of Applied Micro and Nanotechnology (LAMINATE) at National Food Institute Technical University of Denmark (2002). He was promoted as professor at National Food Institute, Technical University of Denmark in 2014. His research focuses on host-bacterial pathogens interaction and applied micro-nanotechnology for rapid detection and identification of pathogens (virus and bacteria). He has worked on several EU and national projects on development of Lab-on-a-chip systems for DNA analysis. These include: DNA array for detection of pathogens (Campylobacterspp, Salmonellaspp, Avian Influenza etc…),solid phase PCR array for early detection of Colon cancer, magnetic, nano and biosensor for sample preparation and nucleic acid isolations and development of total integrated Lab-on-a-chip PCR based systems for on line, at site rapid detection and identification of pathogens (virus and bacteria) in food and animal productions chains as well as in clinical diagnostics.
Abstract:
More than 200 known diseases transmitted through food and food products. In 2011, USA Center Diseases Control and Prevention (CDC) estimated that 1 in 6 Americans (48 million people) get sick with food borne diseases, resulting in 128,00 hospitalization and 300 deaths. The the globalization of agro-food trade is becoming more and more elongated. Foods move across borders and continents in shorter time frames. Consequently, contaminated foods have often been consumed before authorities. Conventional culture methods have been the main workhorses for food safety control, they are expensive, time consuming require sample treatment and inability for onsite testing therefore establishing traceability via cost-efficient rapid and accurate methods for detecting of foodborne pathogens in the entire food chain are urgent need. Micro-fabrication and miniaturisation of biological assays in a so call Lab-on-a-Chips (LOCs) have well known advantages such as greatly reduced reagents consumption, shorter times, faster mixing, high automation, high-throughputs, all leading to reduction of costs .LOCs have been applied in many different contexts (genomics, proteomics, cellomics, immunology etc). However, the fully integrated Lab-Chip remains the main challenge. Recently, via number of national and EU funded projects different total integrated LOC systems for at site rapid detection and identification of food-borne pathogens were developed at DTU. By integrating all the steps from on chip PCR reagents storage, sample preparation to PCR detection in the LOC systems, the pathogens can be on-line or at site rapid detection and identification at sub-species.
Normi Mohd Yahaya
Universiti Putra Malaysia, Malaysia
Title: Hypothetical proteins: Can they be the next drug targets?
Time : 12:20-12:40
Biography:
Normi M. Yahaya has completed herPhD at the age of 25 years from RIKEN Institute and Universiti Sains Malaysia in Molecular Genetics specializing on protein engineering under the RIKEN-Asia Joint Graduate School Program.She later pursued her postdoctoral training in the area of structural biology, specifically in protein nuclear magnetic resonance (NMR) in Institut National Polytechnique de Lorraine, Nancy, France under Center National de la Recherche Scientifique (CNRS). She has won several awards of merit including PACIFICHEM 2010, Young Scholar Award and being one of the Selected Young Scientists for the 60th Meeting of Nobel Prize Winners with Young Scientists in Lindau, Germany.
Abstract:
Hypothetical proteins, also known as orphan proteins, can be found across all genomes of all taxa of life. Despite their considerable number in any given genome, their functional presence and significance is rarely investigated due to their sequence and structural dissimilarity to well-characterized proteins. This further poses challenges on the right approach to be adopted and streamlined when studying these proteins. Using a combination of both genomics and bioinformatics approaches, we streamlined our efforts in mining for hypothetical proteins which are deemed functionally significant, specifically of medical relevance, to be used as potential drug targets in the future. Using the locally isolated Bacillus lehensis G1 alkaliphile as a model, 1,202 hypothetical proteins encoded by its genome were thoroughly analysed using several bioinformatics tools to determine their sequence identity, the presence of functional domains, cellular localization, metal-binding properties, among many others. A hypothetical proteins cluster was accordingly developed based on these data and several hypothetical proteins deemed to be involved in significant processes such as metal-trafficking and antibiotics-degradation/resistance were identified from the cluster. Prediction on their structures, functions and mechanisms were subsequently achieved via in silico protein modelling and docking approaches. Results obtained from this integrated study do reveal that the selected hypothetical proteins have high possibility in carrying our metal-to-protein trafficking and conferring antibiotics-resistance. Such case studies on these orphan proteins highlighted in this present work point to the interesting and very promising notion of using them as the next potential drug targets.
Anders Wolff
Technical University of Denmark, Denmark
Title: Lab-on-a-chip system with integrated sensors for 3D tissue engineering applications
Time : 12:40-13:00
Biography:
Anders Wolff is head of the BioLabChip group at the Department of Micro and Nanotechnology at the Technical University of Denmark: His received his MSc in Chemical Engineering from DTU in 1993 and his PhD in Biochemical Engineering from Delft University of Technology (Delft, The Netherlands) in 1997. He joined the Department for Micro and Nanotechnology (now DTU Nanotech) in 1998. In 2000 he was promote to associated professor and leader of the Cell Handling Group (now BioLabChip group) at DTU Nanotech. Hisresearch focus on various microsystems for cell analysis that included chip flow cytometers with integrated optics, dielectrophoresis for cell handling, sorting and sample preparation, PCR chip, and integrated microsystem for sample preparation and DNA amplification. In recent years his group has also worked on scaffolds for tissue engineering and bioartificial organs.
Abstract:
Organ transplantation is often the primary life-saving medical approach for treatment of several diseases. However, limitations in this procedure such as shortage of donor organs and tissue rejection have motivated research into the development of bio-artificial organs as an alternative approach. Development of a novel, modular, microfluidic lab-on-a-chip system is presented, which is designed to engineer liver tissue in an in vivo mimicking environment. The system incorporates smart bioreactors, designed to support a 3D porous scaffold with embedded cells and integrated sensors for monitoring the development of the tissue. Each bioreactor is designed to accommodate a microporous scaffold having dimensions of 5 x 5 x 5 mm3 and includes spatially distributed bio-impedance based sensors which penetrate the scaffold for real time monitoring of the distribution, proliferation and viability of cells under continuous perfusion conditions. To enable delivery of nutrients and removal of tissue culture waste products, the system also incorporates peristaltic pumps, motors and reservoirs. An array of eight bioreactors are included, to enable parallel tissue culture experiments for optimization of parameters such as flow rate, and to allow screening of various stem cell differentiation factors. The system components are fabricated using a combination of 3D rapid prototyping and microfabrication techniques. Proof of principle is demonstrated by culturing liver cancer cell line (HepG2 cells) in porous scaffolds based on polymers such as PDMS, gelatin, and polylactic acid.
The robust and versatile microfluidic platform presented in this work has a huge potential for 3D tissue engineering applications. The novelty of the device is in the employment of combined micro sensing and polymer scaffold engineering approaches for 3D organ engineering. The use of integrated non-invasive sensing strategies, overcome limitations in traditionally adopted optical techniques, and enable monitoring of tissue development within otherwise inaccessible areas of a 3D tissue construct.
Ryszard Maleszka
The Australian National University, Canberra
Title: Deciphering the epigenetic code with innovative insect models
Time : 13:00-13:20
Biography:
Ryszard Maleszka received his MSc and a PhD in Genetics from the University of Warsaw and has done postdoctoral work at the National Research Council of Canada before moving to Australia in 1987. He is spearheading a research theme called ‘From Molecules to Behaviour’ that uses invertebrate model systems to study the genotype to phenotype link, and to understand how epigenetic networks contribute to environmentally-driven phenotypic plasticity. He is a member of several genomic consortia and advisor to genomic databases. He authored over 135 articles and book chapters including a number of landmark papers in Science and Nature.
Abstract:
The modern field of epigenetics is driven by a deluge of raw sequencing data that reveal a very complex portrait of epigenomic dynamics operating at multiple levels, interacting with each other and remaining in a constant flux. We and others have recently discussed this multifaceted and versatile regulatory network in the context of an epigenetic code as a prime driver of organismal complexity, robustness, plasticity and disease development. We proposed that by providing organisms with a large repertoire of alternative functional interactions, the epigenetic code increases their adaptability to unforeseen environments.But how do we evaluate what these chemical modifications mean in a functional context?How environment is linked to the genome and how external cues are translated into cellular responses via epigenomic changes? When do these changes go above threshold and guide organisms into another direction, such as an alternate developmental trajectory? How does malfunctioning of epigenetic mechanisms result in diseases? To what extent sequence variants such as single nucleotide polymorphism (SNPs) affect epigenomic marks? We are using the social honey bee to develop a framework for explaining the functional significance of environmentally-driven epigenetic modifications in genomic DNA. Specifically, we aim to obtain empirical evidence supporting the idea that epigenomic dynamics is not only influenced by polymorphic changes in DNA, but sequence variants may be necessary to ensure the high level of flexibility of the epigenetic code. We also aspire to shed light on the effects of nutrition on methylation and gene splicing and to determine if the enzymatic machinery implicated in adding/removing epiegenetic marks has sequence specificity.
Maria-João R. P. Queiroz
University of Minho, Portugal
Title: Synthesis and evaluation of new thienopyrimidine/pyridine derivatives as antitumoral and/or antiangiogenics
Time : 14:00-14:20
Biography:
Maria-João Queiroz has completed her first degree in Pharmaceutical Sciences in the University of Porto-Portugal (1986), PhD in Organic Chemistry (1993) in the University of Minho- Portugal and carried out postdoctoral studies in the University of Metz-France (1994). She is Coordinator Researcher since June 2009 and she was the director of the Chemistry Research Centre of the University of Minho from January 2010 to March 2015. She has published more than 110 papers in reputed journals of Organic Chemistry and Medicinal Chemistry and attended to more than 150 conferences around the world. She was also the responsible of several financed projects in Medicinal Chemistry, coordinating different teams.
Abstract:
New thieno[3,4-d]pyrimidines and thieno[3,2-b]pyridines were prepared, fully characterized, and evaluated as antitumor compounds against various human tumor cell lines and/or as antiangiogenics using HUVECs (Human Endothelial Vein Umbilical Cells) that express the VEGFR2 (Vascular Endothelium Growth Factor Receptor-2) which is a trans-membrane tyrosine kinase receptor involved in angiogenesis. Some of our compounds were shown to be active against several human tumor cell lines with low to moderate IC50 values and for the most promising compounds the effects on the cell cycle profile and the induction of apoptosis were studied. The toxicity of these compounds was also studied using a primary porcine liver cell culture established by our group. Some of the compounds prepared, suggested by rational design, were shown to be inhibitors of the phosphorylation of the intracellular domain of tyrosine kinase of the VEGFR2. This mechanism of action of the evaluated anti-proliferation of HUVECs by the BrdU assay in the presence of the compounds was confirmed using western Blott.
Hector Ricardo Galvan Garcia
Dermatology Hospital, Mexico
Title: Onychomycosis: 1064-nm Nd: YAG q-switch laser treatment
Time : 14:20-14:40
Biography:
Hector Ricardo Galvan Garcia has completed his MD at the age 25 years from Guadalajara University and Postdoctoral studies from Institute of Dermatology of Jalisco. He is Director of Hospital Dermatology Dermoquirurgica in Jalisco, Mexico and has published more than 20 papers in reputed journals and serving as an Editorial Board Member of repute.
Abstract:
Laser treatment of onychomycosis is a quick and easy method without complications. Two hundred patients with a KOH (25%) and glycerol (5%) (1 hour at 51-54 °C) for lipid emulsification, and mycological structures were identified under 3400x magnification(+) , onychoscopy (jagged edge and longitudinal striae, positive), confirmed clinical diagnosis of onychomycosis were included in the present study( patients of all ages who had not previously received any type of treatment were included). All of the patients were treated in a single session (with a 1064-nm neodymium-doped yttrium-aluminum garnet (Nd:YAG)q-switch laser (600 mJ 3Hz. Spot 3 mm). There was a 100% clinical response rate within the 18-month follow-up period with no side effects. Thus, this method is proposed as a novel and safe method for the treatment of this ungual pathology, in all of its clinical manifestations, including in the hands and feet and all age groups, without side effects.
Gulacti Topcu
Bezmialem Vakif University, Turkey
Title: Natural cholinesterase inhibitors isolated from anatolian plants
Time : 14:40-15:00
Biography:
Gulacti Topcu obtained her PhD in 1985fromFaculty of Pharmacy at Istanbul University on natural product chemistry, and workedat the University of Illinois at Chicago, College of Pharmacy in the Department of Medicinal Chemistry and Pharmacognosyas a post-doc between 1986-88. She became a full Professor in Organic Chemistry, specifically in Phytochemistry in 1999. Since 2011, she is the Dean of Faculty of Pharmacy, Bezmialem Vakif University at Istanbul. She has published more than 165 papers in reputed journals with more than 2400 citations (h-index:27). She has been serving as the Editor-in Chief of the “Records of Natural Products” which is a SCI journal.
Abstract:
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder, accompanied by dementia, which affects about 38million people worldwide by 2014. The pathogenesis of AD is fairly complex, and besides genetic factors, environmental factors may play important role. Since the cholinergic system plays an important role in the regulation of learning and memory processes, it has been targeted for the design of anti-Alzheimer's drugs. Cholinesterase inhibitors enhance cholinergic transmission directly by inhibiting cholinesterase enzymes, particularly acetylcholinesterase. However, both AChEBuChEenzymes may play an important role in amyloid β aggregation during the early stages of senile plaque formation. The major AD therapeutics available on the market are acetylcholinesterase inhibitors; tacrin, donepezil, rivastigmin and galanthamine besides an NMDA receptor antagonist memantine. But, none of them can provide a satisfactory cure for Alzheimer's disease. Therefore, there is an immediate requirement more efficient drugs than ones prescribed by the physcians at the moment. In our ongoing studies on natural products in drug discovery, we have investigated potential anti-cholinesterase compounds isolated from several plant families. Among them, terpenoids, particularly abietanediterpenoids take an important place in both prevention and treatment of AD, as well as some flavonoids and other phenolics. In this study, a number of compounds including a series terpenoids, flavonoids and a few phenolics isolated from namely Anatolian Lamiaceae family plants have been assayed for anticholinesterase activity tests besides antioxidant and antiradical properties in vitro. The compounds which showed at least 50% inhibition against one of the cholinesterase enzymes at 200 microM were tested in five concentrations to determine their IC50 values.
Xiangqun Xu
Zhejiang Sci-Tech University, China
Title: Approaches for stimulating white rot fungi to accumulate bioactive polyphenols and flavonoids
Time : 15:00-15:20
Biography:
Xiangqun Xu received the BSc degree in Biochemistry from Xiamen University, Xiamen, China, MSc degree in Biochemistry from Zhejiang Medical University, Hangzhou, China, and PhD degree in Biomedical Engineering from Keele University, Keele, UK. She was engaged in Postdoctoral training in Biomedicine in Institute of Biotechnology, Cranfield University, UK. She is currently a Professor in Biotechnology and Biochemical Engineering at Zhejiang Sci-Tech University, Hangzhou. Her current research interests include secondary metabolism of microorganisms and plants, natural products, medicinal mushroom polysaccharides and polyphenols/flavonoids, and medical imaging. She has published more than 50 reputed papers.
Abstract:
Polyphenols particularly flavonoids are important secondary metabolites from the medicinal mushroom Inonotus obliquus. Both the rarity of I. obliquus (white-rot fungus) fruit body and the low efficiency of current method of submerged fermentation lead to a low yield of polyphenols. I. obliquus grown in submerged culture could produce anti oxidative polyphenols. We developed the lignocellulose degradation and stimulatory agent-based approaches for enhancing the simultaneous accumulation of I. obliquus exo-polyphenols (EPC) and endo-polyphenols (IPC). Lignocellulose degradation increased the production and antioxidant activity of extra- (EPC) and intra-cellular (IPC) phenolic compounds. The production of EPC and IPC was significantly enhanced by wheat straw, rice straw, corn stover, sugarcane bagasse and peanut shells. Both of the EPC and IPC extracts from the lignocelluloses containing media showed a higher DPPH radical-scavenging activity than those from the control. The highly active polyphenols/flavonoids such as epicatechin-3-gallate (ECG) and epigallocatechin-3-gallate (EGCG) and phelligridin G significantly increased. Davallialactone and inoscavin B in the EPC extracts were generated in large amounts in the lignocellulose media but not found in the control medium. Linoleic acid was the most effective out of the 17 tested stimulatory agents, the majority of which increased the EPC and IPC production. The addition of linoleic acid resulted in 7, 14 and 10-fold of increase (p<0.05) in the production of EA-EPC (EPC extracted by ethyl acetate), NB-EPC (EPC extracted by n-butyl alcohol) and IPC and significantly increased the production of ferulic acid, gallic acid, ECG, EGCG, phelligridin G, inoscavin B and davallialactone. The EA-EPC, BA-EPC and IPC from the linoleic acid-containing medium had significantly (p<0.05) stronger scavenging activity against DPPH radicals which was attributed to the higher content of these bioactive polyphenols and flavonoids. The combination effect of lignocellulose degradation and stimulatory agents was evident.
Zhonglin Tang
Chinese Academy of Agricultural Sciences, China
Title: Systematic identification and characteristics of long non-coding RNAs in pigs
Time : 15:20-15:40
Biography:
Zhonglin Tang has completed his PhD from Huazhong Agricultural University and Postdoctoral studies from Institute of Animal Science, Chinese Academy of Agricultural Science (CAAS). He is the PI of Agricultural Genome Institute at Shenzhen, CAAS. His field of interest is functional genomics and expression regulation of skeletal muscle in pig and mouse. He has published more than 44 papers in reputed journals and has been serving as an Editorial Board Member of repute.
Abstract:
The long non-coding RNAs (lncRNAs) are non-protein coding RNAs and involve in a variety of biological processes. Pig (Susscrofa) is an important farm animal and ideal biomedical model. In this study, we performed a genome-wide scan of lncRNAs in pig. Based on strand-specific RNA-Seq data, a computational method was used to identify 96,314 novel lncRNAs candidates in pig genome which included 39,528 large intergenic ncRNAs (lincRNAs), 180 nature antisense transcripts and 56,606 intronic ncRNAs. Novel lncRNAs show fewer exon number, shorter transcripts length, lower GC content, expression and conservation level, higher SNP density than protein-coding transcripts. To validate the result, we perform RT-PCR to detect selected lncRNAs. Expression analysis of 5 abundant lncRNAs was conducted by quantitative PCR (qPCR) in 9 tissues of Landrace pigs in 160 days post-coitus (dpc). We first performed identification and characterization of pig lncRNAs using strand specific RNA sequencing. Our study significantly expanded the number of pig lncRNAs in non-protein coding RNA database and provided important information for functional studies.
- Track 4: Cell Biology, Track 5: Tissue Biology, Track 6: Developmental Biology
Location: Valencia B, Melia Valencia
Chair
Anja Nohe
University of Delaware, USA
Co-Chair
Nirmal K. Shetty
Shri Krishna Research Centre, India
Session Introduction
Anja Nohe
University of Delaware, USA
Title: Identifying new targets to improve skeletal formation in human
Time : 09:00-09:20
Biography:
Anja Nohe is an associate professor in the Department of Biological Sciences at the University of Delaware. She received her PhD in Chemistry in 2000. After a postdoctoral fellow at the University of Western Ontario in Canada, she accepted a first faculty position at the University of Maine in Chemical and Biological Engineering. In 2008 she relocated to the University of Delaware. She is a member of several editorial boards and her research is currently funded by the National Institute of Health. She uses novel imaging approaches such as AFM and the family of Image Correlation Spectroscopy to define cellular processes during stem cell differentiation and skeletal formation. Moreover, utilizing novel techniques and tools such as real time imaging and nanoparticles, she focuses on protein dynamics in cells as well as on protein distribution in mice.
Abstract:
Humans rely on their skeleton during their lifespan for several crucial functions as diverse as body support, walking, and energy balance. Unfortunately, during aging the human skeleton loses bone mass and its function is impaired. This leads to diseases such as Osteoporosis. A woman’s risk of breaking a hip due to osteoporosis is equal to her risk of breast, ovarian and uterine cancer combined. And a man age 50 or older is more likely to break a bone due to osteoporosis than he is to get prostate cancer. For most bone diseases, new innovative treatments and therapeutics are needed. However, in order to develop these the formation of the skeleton and the skeletal changes in adults must be determined. Bone is a dynamic living tissue that hosts a variety of different cell types embedded into mineralized matrix. Bone morphogemetic protein 2 (BMP2) is a growth factor that drives stem cell differentiation and bone growth in vivo. However, it has several side effects, when being used in the clinic. Therefore therapeutics and treatments based on the signaling pathway of BMP2 may show great potential to induce skeletal growth. Using a systems biology approach we modeled the BMP2 signaling pathway and defined key targets in the BMP2 signaling pathway. We confirmed their role using atomic force microscopy combined with fluorescent microscopy. Moreover, we developed a peptide that activates specific signaling pathway in vitro and in vivo. We showed that systemic injection of this peptide in mice causes increase in bone mineral density and mineral apposition rate as well as trabecular thickness. These results suggest that the peptide is a powerful mediator of skeletal growth and may be used to improve skeletal formation in adults.
Imre Olah
Semmelweis University, Hungary
Title: Organization of avian thymic medulla and surfactant production
Time : 09:20-09:40
Biography:
Imre Olah has completed his MD at age of 24 from Semmelweis University Faculty of Medicine. His PhD and DSc were completed from Hungarian Academy of Sciences. His postdoctoral studies were made at the Anatomy, Histology and Embryology Department, Semmelweis University. He worked as Research Associate in Department of Biological Structure, Washington State University Seattle, Poultry Science Department Mississippi State University, and Clemson University South Carolina. He was professor and Head of Department of Human Morphology and Developmental Biology, Semmelweis University. He has published more than 130 papers, and book chapters. Recently professor emeritus
Abstract:
Thymic medulla of the chicken is compartmentalized to 1.) keratin positive network (KPN), and 2.) keratin negative areas (KNA). KPN is connected with the cortical epithelial reticular cells (ERC) and the KNA is a dilation of the interlobular septae consisting of reticular connctive tissue. “Derailed” differentiation or development of thymic ERC results in thymic cyst and/or Hassall’s body’s formation. Both cysts and Hassall’s bodies locate in the KPN of thymic medulla. Possibly, the differentiation of the cells of the thymic cyst and Hassall’s body‘s cells stopped in the early and late stages of development, respectively. The thymic ERC and the surfactant producing type II pneumocytes of the lung develop from the foregut endoderm. The transmission electron microscope shows, that the cells of the multicellular cysts are polarized and the structure of the cytoplasmic granules identical with that of the type II pneumocytes. At the apical side of the cyst epithelial cells express alpha smooth muscle actin. The lumen of the cysts is filled with a substance of medium electron density and strongly stained with anti-surfactant SP-B. These findings indicate, that the cyst epithelium actively secretes surfactant, which contribute to the central tolerance of thymus, and innate immunity. The thymic ERC and the surfactant producing epithelial cells of the cysts express MHC class II antigen unlike the type II pneumocytes.
Jamila Chakir
Laval University, Canada
Title: Regulatory role of microRNA in severe asthma
Time : 09:40-10:00
Biography:
Jamila Chakir is a full professor, department of Medicine at Laval University and Institut Universitaire de Cardiologieet Pneumologie de Québec. She obtained a PhD degree in Immunology in France. She received postdoctoral research training at Laval University and McGill University, Canada in inflammation and remodeling in asthma. Dr Chakir’s research focuses on cellular and molecular mechanisms of airway remodeling. She has published more than 200 papers, communications and book chapters in the respiratory and immunology field and holds grants from Canadian agencies. She is amember of different national and international scientific committees and has received several awards from national and international organisations.
Abstract:
Allergic asthma is a chronic inflammatory disease characterized by an airway hyper-responsiveness and a deregulated inflammation in response to allergens. Available treatments are mainly symptoms-driven and do not interfere with the natural history of the diseases. Severe asthma constitutes a challenging problem for the healthcare system. Its heterogeneity complicates the management of the disease. There is a significant need to understand the pathogenesis of severe asthma. Bronchial epithelium is considered a key player in coordinating airway wall remodelling. While, in mild asthma, the epithelium is damaged and fails to proliferate and to repair in severe asthma the epithelium was reported to be highly proliferative and thicker. This may be due to different regulatory mechanisms. We studied microRNAs profile and evaluated their role in regulating proliferation of bronchial epithelial cells obtained from severe asthmatic subjects in comparison to cells obtained from mild asthmatics and healthy controls. We found that in mild asthmaepithelial cells produce high amount of TGFï¢1 and express high level of TGFï¢-RI and phosphorylated-Smad3, indicating that TGFï¢1signallingis up-regulated. In severe asthma, this pathway was down-regulated. Thus, in epithelial cells from severe asthmatics compared to mild asthma and controls, miR-19a, a member of the miR-17~92 cluster, is up-regulated and increases proliferation. Knockdown of miR-19a in epithelial cells reduces significantly their proliferation through targeting TGF-ï¢ downstream signaling. Our study uncovers a new regulatory pathway involving miR-19a that is critical to the severe phenotype of asthma and indicates that down-regulating miR-19a expression could be explored as a potential new therapy to modulate the epithelium repair in asthma (Funded by the CIHR).
Helena Barreto Henriksson
Sahlgrenska University Hospital, Sweden
Title: Stem cell biology and applications in preclinical experiments
Time : 10:00-10:20
Biography:
Helena Barreto Henriksson is active in the regenerative medicine research field since 10 years with main focus on molecular regenerative features of cartilage. Currently, Helena is working as a researcher at the Dept. of Orthopaedics, Sahlgrenska University hospital/Gothenburg University, Sweden in the translational medicine field; “from preclinical to new clinical approaches” e.g. stem cell therapy for degenerated intervertebral discs as well as studying local tissue specific stem cell populations in the disc. Helena Barreto Henriksson finished her PhD studies (Medical Science) at Gothenburg University, 2010 with the thesis “Intervertebral disc regeneration, Studies on stem cell niches and cell transplantation.
Abstract:
Regenerative medicine is a rapidly increasing research field worldwide. In this field, cell therapy applications involving mesenchymal stem cells(MSCs) are currently under investigation, some applications are already in clinical use. Cell sources for clinical treatments in clinical use are e.g. bone marrow derived MSCs. Low back pain is common in the Western world and intervertebral disc(IVD) degeneration is considered to be a major cause.Recently, stem cell therapy has been discussed as alternative treatment option for degenerated IVDs where the purpose would be to repair, maintain, or enhance the function of particular cell typesin the IVD.Further, normal cell proliferation and regeneration in the IVD are at present sparsely investigated. Cartilage is considered to lack/have a poor capacity of self-repair. However, studies have identified progenitor-/stem cells in cartilage(different mammalian species)and data point in direction that adult IVDs have a regeneration capacity, however slow.The possibility to stimulate local cells in situ would be an interesting biological treatment option. Preclinical experiments e.g. xenotransplantation animal models are useful for evaluation of e.g. the local microenvironment effects that MSCs will encounter after transplantation. We have investigated cellular migration and tissue distribution of transplanted MSCs bynon-toxic pre-labeling e.g. iron compoundsfor tracing in vivo as well as monitoring effects of different biomaterials e.g. cellular motilityon aligned collagen fibres coated surfaces (time-lapse methods). In conclusion, stem cell therapy using MSCs and/or to stimulate local stem-/progenitor cells hold a high promise for development of biological treatment options for degenerated cartilaginous tissues.
Bernardo L Trigatti
McMaster University. Canada
Title: High density lipoprotein signaling in macrophages and its role in atherosclerosis protection.
Time : 10:35-10:55
Biography:
Bernardo L Trigatti has completed his PhD in 1995 at McMaster University and postdoctoral studies from the Massachusetts Institute of Technology before re-joining McMaster University’s Department of Biochemistry and Biomedical Sciences in 2000. He is an Associate Professor at McMaster University and joined the newly formed Thrombosis and Atherosclerosis Research Institute in 2010. He is leading a lab group focusing on uncovering molecular pathways involved in the development of atherosclerosis and associated cardiovascular disease.
Abstract:
Macrophages play key roles in the development of atherosclerosis, a leading cause of coronary heart disease, stroke and peripheral vascular disease. Macrophages participate in all stages of atherosclerotic plaque formation. Lipid laden macrophages accumulate in developing atherosclerotic plaques. Macrophage apoptosis contributes to the development of lipid rich, cell free necrotic cores within atherosclerotic plaques, a key feature of the so-called vulnerable plaque. Vulnerable plaques with large, unstable necrotic cores are prone to rupture, resulting in occlusive and potentially devastating athero-thrombosis. High density lipoproteins (HDL) protect against the development, contribute to the stabilization and also trigger the regression of pre-established atherosclerotic plaques. Recent studies have revealed that HDL, in addition to its well established role in mediating cholesterol removal from atherosclerotic plaques, can also act as a signaling molecule in a variety of cell types. Our studies have explored the ability of HDL to trigger signaling events in macrophages activating pro-survival and migratory responses. These contribute to the protection of macrophages against apoptosis in atherosclerotic plaques, limiting the formation of necrotic cores, as well as the stimulation of macrophage egress from plaques, promoting the regression of pre-established atherosclerotic plaques. Identification of the signaling pathways involved in these processes will allow us to identify new therapeutic targets for plaque stabilization and to induce atherosclerotic plaque regression.
Nirmal K. Shetty
Shri Krishna Research Centre, India
Title: New nomenclature for pedigree charts based on the novel pattern of inheritance of ancestral and parental chromosomes
Time : 10:55-11:15
Biography:
Nirmal K Shetty is the Director of Shri Krishna Research Centre, Mumbai, India. He graduated from Madras Medical College, India, and studied Acupuncture in Shanghai, China. He is also a Consulting Acupuncturist for over two decades, and is associated with Cumballa Hill Hospital, Inlaks General Hospital and Shanti Avedna Cancer Hospice. His study focuses on innovative theoretical research at the interface, with the objective of giving a new perspective to inheritance of chromosomes. The study hopes to open new fields of research in future that may help in finding solutions to some genetic disorders and cancer.
Abstract:
A new nomenclature for pedigree charts was developed based on a fundamental new hypothesis which depicts a novel pattern of inheritance of ancestral and parental chromosomes. It gives a new dimension to the inheritance of hereditary traits. Of the two sex chromosomes XX or XY, the first chromosome ‘X’ represents ancestral and the second chromosome X or Y represents parental viz., mother or father respectively, autosomes are also differentiated in the same manner. In the pedigree charts, suffix numbers are given in sequential order to ancestral sex chromosomes and parental sex chromosomes separately depicting married partners as well. Applying the new nomenclature for pedigree charts gives better clarity with regard to inheritance of hereditary characteristics. This could help in genetic counseling and in understanding better, how some types of consanguineous marriages predispose their offspring to genetic disorders and that one type of consanguineous marriage does not affect the offspring. The new hypothesis is based on innovative theoretical research at the interface. Principle of opposites, Barr body, gene recombination during chiasma and natural selection, all play an important role in pre-determining the pattern of inheritance of chromosomes at the time of fertilization leading to the formation of the zygote. This hypothesis opens new fields for research in biology and genetics and may help future research in finding cures for some genetic disorders and cancer.
Jim Karagiannis
University of Western Ontario, United Kingdom
Title: On the computational ability of the RNA polymerase II carboxy terminal domain
Time : 11:15-11:35
Biography:
Jim Karagiannis is an associate professor at the University of Western Ontario in London, Ontario, Canada. His research makes use of the model eukaryote Schizosaccharomyces pombe and explores the complex post-translational modifications that take place on the carboxy-terminal domain (CTD) of the largest subunit of RNA polymerase II. Through an empirical examination of the informational properties and regulatory potential of the CTD, Dr. Karagiannis hopes to decipher the “programming language” used by eukaryotes to control aspects of gene expression.
Abstract:
The RNA polymerase II carboxy terminal domain has long been known to play an important role in the control of eukaryotic transcription. This role is mediated, at least in part, through complex post-translational modifications that take place on specific residues within the heptad repeats of the domain. In this report, the phenotypic effects of systematic site-directed mutations in the fission yeast RNA pol II carboxy terminal domain (CTD) are investigated. Remarkably, we find that alterations in CTD structure and/or phosphorylation result in distinct phenotypic changes related to morphogenetic control. A hypothesis based upon the concepts of “informational entropy” and “algorithmic transformation” is developed to explicate/rationalize these results. In addition, a formal mathematical conceptualization of CTD modification (in the form of a semi-Thue string rewriting system) is presented. Since the semi-Thue formalism is known to be Turing complete, this raises the possibility that the CTD – in association with the regulatory pathways controlling its post-translational modification – functions as a biological incarnation of a universal computing machine. These ideas imply that the controlled manipulation of CTD effectors could be used to “program” the CTD and thus to manipulate biological processes in eukaryotes in a definable manner.
Yunfeng Zhou
Wuhan University, China
Title: Telomere/telomerase and radiosensitivity
Time : 11:35-11:55
Biography:
Yunfeng Zhou has completed his PhD/MD in 1991 from Lyon University, France. He is the Director of Hubei Cancer Clinical Study Center, Hubei Key Laboratory of Tumor Biological Behaviors and Hubei Radiotherapy quality control center. His main research fields including telomere/telomerase in anti-cancer therapy and radiation-guided gene therapy of cancer. In addition to being an outstanding oncologist, he was committed to Sino French medical exchange. Due to his great contributions, the French Government awarded him French Knight Badge (2006) and National Order of the Legion of Honour (2009). He published more than 100 papers in international and national journals.
Abstract:
Radiotherapy is the major method of malignant treatment and the high radioresistance of tumor cells is still the significant reason for the failure of radiotherapy. So identifying new factors that predict radioresistance is an area of intense research and could be of great value in the treatment of cancers. Based on our research during the past 15 years, we find that telomere, telomerase and telomere-binding proteins are important regulators of radiosensitivity. Firstly, our study indicated that telomere length may be used as a promising tool to predict the radiosensitivity of human carcinomas. Further, we found that telomerase and telomere-binding proteins (TPP1, POT1, TRF2 and CTC1) are effective radiosensitization targets in cancer radiotherapy. Moreover, our research team combine CArG element with hTERT promoter to form a new kind of chimeric promoter, which combines gene with ray skillfully and treat tumor with local therapy as well as inducing the expressing of therapeutic gene. Our research team has successfully construct a new kind of chimeric promoter system based on hTERT and verified its radiosensitization effect in cervical cancer, lung cancer and liver cell model. In summary, our research demonstrated that telomere, telomerase and telomere-binding proteins are effective radiosensitization targets in cancer radiotherapy. Now our research mainly focuses on their mechanisms of the radiation-sensitizing effect.
Hui Yang
Wuhan university, China
Title: Carboxyl terminus of Hsp70-interacting protein(CHIP) functions as a tumor suppressor and enhance the radiosensitivity in cervical cancer
Time : 11:55-12:15
Biography:
Hui Yang is a PhD candidate of Wuhan University, China. She took part in the group of Prof. Yunfeng Zhou who has been the head of Zhongnan Hospital of Wuhan University and research on the telomere/telomerase in anti-cancer therapy and radiation-guided gene therapy of cancer.
Abstract:
Cervical cancer recurrence and metastasis after radiotherapy is one of the main reasons lead to cervical cancer treatment failure. CHIP serves as a chaperone-associated Ubox-containing E3 ligase that can modulate a lot of tumor-related proteins and has been reported to act as an tumor suppressor in pancreative cancer, breast cancer, colorectal cancer and so on. But we know little about its roles in cervical cancer. In this study, we show a significant difference in the expression of CHIP between the normal squamous cervical epitheilia, high grade squamous intraepithelial lesions and invasive squamous cell carcinoma of the cervix tissues. Gene set enrichment analysis(GSEA) shows that the CHIP is related to cell cycle progression, cell apoptosis and DNA damage pathways. So we hypothesis that CHIP can modulate the radiosensitivity in cervical cancer. Here, we established two radioresisitant cervical cancer cell lines C33AR and HelaR by exposing their parental C33A and Hela cells to repeated X-ray irradiation with a total dose of 60Gy and 72Gy respectively. The radiosensitivity of these two pairs of radiosensitive and radioresistant cell lines were confirmed by clonogenic assays. We then examine the cell cycle distribution and cell apoptosis by flow cytometry and found that the radioresisitant cell lines prolonged G2 arrest and lesser apoptosis which compared to their parent cell lines after 6Gy X-ray irradiation. Furthermore, transwell, real-time PCR and TeloTAGGG telomerase PCR ELISA Kit were performed to examine cell invasion, telomere length and telomerase activity in these two pairs of cell lines separately and the C33AR and HelaR cell lines show a significant difference in cell invasion, telomere length and telomerase activity. In addition to this, real-time PCR and western blot were used to examine the expression of CHIP and hTERT respectively and show that the CHIP is low expressed in radioresistant cell lines, whearas the hTERT is high expression in radioresisitant cell lines. In order to further explore the relationship between CHIP, hTERT and radiosensitive, we use real-time PCR to detect the expression of CHIP and hTERT at different time points after 2Gy, 5Gy and 10Gy irradiations, the results show that the CHIP expression is accompany with the changing of hTERT, a few minutes after the high expression of hTERT, the CHIP is high expression and then the expression of hTERT is declined. Overexpression of CHIP in C33AR and HelaR cell lines show an enhancement of radiosensitivity and down regulate telomerase activity. These results showed that CHIP can be seen as a tumor suppressor and high expression of CHIP can enhance the radiosensitivity by negatively regulates telomerase activity. Hence, CHIP may served as a novel target radiosensitizer.
Ewa Maj
Polish Academy of Science, Poland
Title: Antiangiogenic treatment in non-small cell lung cancer (NSCLC)
Time : 12:15-12:35
Biography:
Ewa Maj is PhD student at Institute of Immunology and Experimental Therapy, PolishAcademy of Science. She has completed her M.Sc. of Biotechnology from University of Agriculture in Krakow and also M.Sc. of Medical Analytics from Jagiellonian University Medical College in Krakow. Before Ph.D. studies she worked in Laboratory of Autoimmunology in “Diagnostyka Medical Laboratories” as medical technologist.She has published about 9 papers as co-author in reputed journals and presented results of her research on a national and international conferences.
Abstract:
Lung cancer is the leading cause of cancer-related deaths worldwide. Due to lack of early symptoms patients are diagnosed with advanced stage of the disease. Growing tumors promotes angiogenesis inside malignant tissue, what next results in metastatic potential and poor prognosis. Tumor angiogenesis is one of the targets for anticancer therapy developed today. Malignant cells, including lung cancer cells, release many growth factors that are involved in tumor angiogenesis. Blocking signal transduction pathway of VEGF, main angiogenicfactor, by for example VEGF receptor inhibitors or anti-VEGF monoclonal antibodies results in endothelial cells apoptosis what in turn blocks angiogenesis. Recently it was discovered, that tumor suppressor p53 protein is involved in controlling tumor vascularization. In cancer tissue samples obtained from patients with lung cancer,immunohistochemical analysis showed that mutant p53 correlated with higher VEGF expression. In our study we decided to combine some tyrosine kinase inhibitors(TKI) with cytostatics: cisplatin and docetaxeland also calcitriol analog as a proposed treatment in non-small cell lung cancer (NSCLC) model. The research focused on combined effect of above mentioned drugs towards proliferation of lung cancer and endothelial cells and the VEGF production by cancer cells in vitro. The mechanism of observed downregulation of VEGF expression in lung cancer cells after exposure to combination of TKI with cytostatics was explored.
Justyna Trynda
Polish Academy of Science, Poland
Title: The role of microRNA-125b in calcitriol-induced differentiation of human leukemia and lymphoma cells
Time : 12:35-12:55
Biography:
Justyna Trynda is PhD student at Institute of Immunology and Experimental Therapy, Polish Academy of Science. She has completed her M.Sc. of Biology from University of Agriculture in Wroclaw and also Molecular Biology from Jagiellonian University in Krakow. Before Ph.D. studies she worked in Laboratory of Electron Microscopy in University of Agriculture in Wroclaw as senior technician. She has published about 2 papers as co-author in reputed journals and presented results of her research on a national conferences.
Abstract:
MicroRNAs are short (~22 nucleotides) single strands of RNA that function as regulators of mRNA translation. They have integral roles in a broad array of biological processes. Many microRNAs are implicated in the anticancer action of calcitriol (active form of vitamin D). One of the most important is miR-125b known as regulating vitamin D receptor (VDR) and vitamin D 24-hydroxylase- CYP24 expression. Moreover, miR-125bhave been reportedto be involved in a variety of cancers regulating cell cycle, differentiation and apoptosis by targeting a number of genes such as transcription factors, matrix-metalloproteases, members of Bcl-2 family, p53, NF-κB.The aim of our work was to study the role of miRNA-125b in anticancer activity of calcitriol in human leukemia and lymphoma cells. In our experiments we measured the expression of microRNA-125b after calcitriol treatment and correlated it with the level of mRNA and protein e.g. vitamin D receptor, vitamin D 24-hydroxylase- CYP24, membrane associated rapid response steroid receptor ERp57,and others, which are responsible for differentiation of cells. We conclude that microRNA-125b may regulates crucial molecules engaged in differentiation process of human leukemia and lymphoma cells after exposure to calcitriol.
Abdel-Hamid
National research centre, Egypt
Title: Diagnosis of dengue infection using metabolome analysis (biomarker profiles)
Time : 12:55-13:15
Biography:
Abdel-Hamid Zaki, Deputy of Pharmaceutical and Drug Industries Division (NRC). He was appointed as a head of Therapeutic Chemistry Department, National Research Centre, (2006, 2012)). He is working as professor of Applied Biochemistry at the same department. Major field of his interest is metabolomics in pharmaceutical research. He awarded many of scientific mission and grants from DANIDA (Denmark – 1994), TWAS (Italy-1997, 2001, 2003), FAPESP (Brazil, 2001),and UNESCO (2002). Abdel-Hamid was obtained and held PI for 5 international research projects from ISESCO- (1990-1993), TWAS- (1995-1996),TWAS ( 1998-1999), TWNSO- (2004-2006) and STDF (2014-2016).
Abstract:
Dengue is a major health and pressing threat to Malaysia with increasing atypical manifestations. In this study, metabolomics approach was used to identify metabolite candidates by means of 1H NMR- spectrometry as a diagnostic tool for dengue disease. The mid-stream urine collected from 52 patients diagnosed with dengue fever at Penang General Hospital and 43 healthy individuals was analyzed with 1H NMR spectroscopy, followed by chemometric multivariate analysis. NMR signals which highlighted in the OPLS-DA S-plot were selected and identified using Human Metabolome Database (HMDB) and Chenomx Profiler. A highly predictive model was constructed from urine profile of dengue infected patients versus healthy individuals with the total R2Y (cum) value is 0.935, and the total Q2Y (cum) value is 0.832. The differences between infected patients versus healthy individuals were found to be related to amino acid metabolism, tricarboxylic acid intermediates cycle and β-oxidation of fatty acids. Distinct variations in certain metabolites were recorded including amino acids, various organic acids, betaine, valerylglycine, myo-inositol and glycine. The results open up a possibility of rapid, non-invasive analysis and diagnosis of dengue disease using urine metabolic profile.
- Track 7: Bio-Engineering, Track 8: Systems Toxicology, Track 9: Ecology and Evolution
Location: Valencia B, Melia Valencia
Chair
Armando del RÃo Hernández
Imperial College London, United Kingdom
Co-Chair
Witold Chmielewski
Laval University, Canada
Session Introduction
Adam Qingsong Ye
James Cook University, Australia
Title: Design of nano-controllable release system for bone regeneration in craniofacial defects
Time : 10:00-10:20
Biography:
Adam Qingsong Ye, obtained his DDS, MDS,PhD (Ortho.),PhD (Med. Sci.) from China and the Netherlands. He is a Diplomate of Royal College of Surgeons of Edinburgh in Orthodontics, elected fellow of Royal Society of Medicine, UK, foundation member and coordinator of the orthodontic postgraduate program at James Cook University, AU. He has published about 40 articles with high impact factor and co-authored a P/G textbook entitled Evidence-based Stomatology. He is also an ARC DECRA Fellow, and founder and leader of the Craniofacial and Orthodontic Research (CORE) group. He is Associate Editor of the Journal of World Federation of Orthodontists (JWFO) and Journal of Investigative and Clinical Dentistry (JICD), President of the Asia Pacific Orthodontic Forum, regular referee for international journals and grants.
Abstract:
Cleft lip and palate is the most common birth deformity of the face, and occurs in one of every 600-800 newborns. Cleft lip and palate is believed to be a multi-factorial process, involving genetic and environmental factors. Approximately 75% cleft patients have an osseous defect in the alveolus, which could affect the normal development of a child’s appearance and speech. The conventional strategy for the reconstitution of bone defect largely relies on multi-surgical procedures of bone grafts. One major shortcoming with regard to this technique is the absorption of the implanted bone grafts. The implantation of auto-bone graft or artificial bone substitutes always causes an inflammatory response, i.e. foreign body reaction, which induces the degradation of the implanted bone grafts. Recent Cochrane systematic review has shown inconclusive results with this method. In order to prevent the inflammatory reaction against implanted bone grafts and to prevent the multi-surgical procedures in the treatment of cleft, a novel strategy to repair bony defects through an endogenous bone regenerative technique was proposed. This method bases on a nano-delivery release controlled system and applies the patient’s own regenerative ‘facilities’, e.g. patient-derived growth factors, to build up a scaffold niche in the defected site where the stem cells/progenitor from neighboring tissues can be recruited for in situ regeneration of the hard tissue.
Mahmoud Rouabhia
Laval University, Canada
Title: Repeated exposure to cigarette smoke increased gingival fibroblast proliferation, telomerase activity through the activation of cell cycle genes activity
Time : 09:00-09:20
Biography:
Mahmoud Rouabhia is a full Professor at the Faculty of Dentistry of Laval University. Pr. Rouabhia is a senior scientist in the field of Immunology, cell biology, and tissue engineering. He got his Ph.D in France, followed by a postdoctoral training for four years in Canada. His research interest includes studying the interaction between host & oral microorganisms, the role of local innate immunity, investigating the tobacco effect on the oral cavity, etc. Professor Rouabhia has more than 130 pair reviewed scientific publications. He is the editor/coeditor of three books. He published over 15 book chapters/review articles, and two patents.
Abstract:
The aim of this study was to investigate the effect of repeated exposure to cigaarette smoke condensate (CSC) on the survival, oncogenes profiling, telomere length and telomerase activity of primary human gingival fibroblasts.Methods: Primary human gingival fibroblasts were exposed three times a day, during 15 min to CSC at one of the following concentrations: 0, 2, 5 or 10%. The exposure periods were 10, 20 or 30 days. Cell proliferation was evaluated by mean of BrdU assay. Oncogenes & Tumor Suppressor Genes profiling was performed by using PCR Array. Protein telomerase detections were determined by protein telomerase assay. Telomere restriction fragment analysis was performed using the TeloTAGGG Telomere Length Assay Kit. Results: Exposure to low concentrations of CSC led to a significant increase in cell proliferation. CSC modulates the oncogenes pathway increasing CDK4, SRC JUND, NFKBIA and PIK/CA but decreasing other genes such as CASP8, RARA. Tumor suppressor genes pathway mostly showed repressed genes such as BRCA2, WWOX and BRCA1. When analyzing apoptosis genes pathway, multiple genes were repressed including BCL2, MCL1. Apoptotic gene activation is supported by the repression of those genes involved in cell cycling were we found decreased expression of TP53, CCND1 and BRCA2. The telomerase activity was significant (p <0.01) increase in CSC cells, supporting the telomere length shortening. Conclusion: Overall, this study demonstrated that cigarette smoke deregulates cell cycle genes, with potential cell mutation and cancer initiation/ development (funded by the U. Laval Foundation, Fonds Émile-beaulieu).
Fatemeh Bahadori
Bezmialem Vakif University, Turkey
Title: Apolipoprotein E4 mediated targeting of blood brain barrier using nano-micellar metal chelators for treatment of Alzheimer’s disease
Time : 09:20-09:40
Biography:
Fatemeh Bahadori has completed his PhD from Istanbul Technical University. He is Assistant Professor at Faculty of Pharmacy, Department of Pharmaceutical Biotechnology, Bezmialem Vakif University. He has published more than 11 papers in reputed journals and has been serving as Vice Director of Institute of Health Sciences, Bezmialem Vakif University since 2014.
Abstract:
Alzheimer’s Disease (AD) is one of the most important disorders of current century. Many pathological factors are contributed in the progress of this disease, the most important one being aggregation of Amyloid β (Aβ) in brain. Thus, prevention of Aβ aggregation could have an important role in the treatment of AD. It is well-defined that some divalent metals namely iron, copper and zinc play role in Aβ aggregation. Thus, formulations with metal-proteinattenuating (MPA) and metal chelating activity (metal chelators (MCs))could play a possible role as co-treatment agents for AD.However,MCs are generally neurotoxic and more importantly, they are hydrophilic which means they wouldn’t pass through Blood Brain Barrier (BBB). Since the structure-activity relationship of MCsis defined as carrying oxygen bearing functional groups in ortho position, we chose series of plants, which are rich in poly-phenolic compounds with this special property. We also chose a series of synthetic compounds with high MC activity. Plant extracts were prepared and screened for their MC and MPA activity by incubating with Aβ aggregates. The methanolic extract of Rosmarinusofficinalis(RO) showed the highest metal chelating and metal protein attenuating activity while PyrrolidineDithiocarbamate (PDTC) was the most active and non-toxic synthetic material. Nano-micellar Poly Lactic-co-Glycolic Acid (PLGA) formulation of RO and PDTC was prepared and surface modified with Apolipoprotein E4. Both formulations showed satisfying MPA and MC activity with a hydrodynamic size less than 200 nm, while, Apo E4 provided targeting property using its specialized receptors on BBB.
Masato Sone
Tokyo Institute of Technology, Japan
Title: Integration of biocompatible MEMS by gold electrodeposition using supercritical carbon dioxide
Time : 09:40-10:00
Biography:
Masato Sone completed his doctor degree of engineering at the age of 28 years old at Tokyo Institute of Technology. He worked as a researcher in Nippon Oil Company from 1996-2000. He was an assistant professor and then a research associate professor at Tokyo University of Agriculture & Technology from 2000 to 2005, and he got the position of associate professor at Tokyo Institute of Technology from 2005 until present time. He has published more than 110 papers in scientific journals. His majorities are microelectronics, surface finishing, chemical engineering, liquid crystal and polymer science. His recent topic has been novel nano wiring process using supercritical carbon dioxide for integrated circuit technology.
Abstract:
The flexible properties of polymeric material make bio-MEMS promising candidates for the next generation of micro devices. However there have been many difficulties to overcome in fabrication process. Supercritical carbon dioxide (sc-CO2) is generally viewed as a replacement for harmful organic solvents used in extractions, separations, chemical reactions, molding, and many other applications because CO2 is non-polar and the tunable physical properties between a gas and a liquid. Especially for application of sc-CO2 in fine wiring technology, transfer of materials into and out of fine nano-space can be improved to allow proper cleaning and complete filling of the nano-spaces. Thus we have studied an application of sc-CO2 into integration of bio-compatible MEMS. We examined sc-CO2 for washing of photoresist pattern on substrate and completed washing the pattern with strengthening the adhesion. We have also proposed a washing process using emulsion of sc-CO2 in water for eliminating the resist pattern from the substrate. We now have studied metalizing of gold on polyimide, which is composed of catalyzation process on/into polymer using sc-CO2 of Pd-organic complex and electroless plating using sc-CO2 emulsion (ELP-SCE), which is composed of an aqueous electrolyte, sc-CO2, and a surfactant. ELP-SCE enabled the penetration of Pd into deep-inside of polymer. So Pd seed-layer can be deposited on polyimide. We also have studied gold electroplating method using sc-CO2 emulsion (EP-SCE). Metal film obtained by this technique was uniform and without pinhole, because sc-CO2 has low viscosity and compatibility of hydrogen. Thus, we have proposed and examined a void-free gold wiring on the Pd seed layers/polyimide. This method is applicable into bio-compatible MEMS.
Daisuke Yamane
Tokyo Institute of Technology, Japan
Title: Nano-G metrology system and its biomedical applications by CMOS-MEMS technology
Time : 10:00-10:20
Biography:
Daisuke Yamane received the B.S., M.S., and Ph.D. degrees in electrical and electronic engineering from The University of Tokyo, Tokyo, Japan, in 2006, 2008, and 2011, respectively. From 2010 to 2012, he was a Research Fellow of the Japan Society for the Promotion of Science hosted within the Research Center for Advanced Science and Technology, The University of Tokyo. From 2011 to 2012, he was a Visiting Scholar at the University of California, Los Angeles, CA, USA. Since 2012, he has been an assistant professor with Precision and Intelligence Laboratory, Tokyo Institute of Technology, Kanagawa, Japan. His research interests include radio-frequency (RF) microelectromechanical systems (MEMS), MEMS inertial sensors, and (complementary metal-oxide semiconductor) CMOS-MEMS technology.
Abstract:
MEMS (microelectromechanical systems) technology has enabled micro-scaled capacitive accelerometers to be widely available in consumer electronics for the sensing range to be mostly above 1 G (9.8 m/s2). In recent years, accurate sensing of low acceleration, specifically below 1 G (9.8 m/s2), has been one of the major interests for MEMS accelerometers to be used for applications such as human-activities monitoring or the integrated inertial measurement unit. The commercialized MEMS accelerometers exhibit, however, insufficient performance for sub-1G sensing due to the mechanical noise that determines the sensitivity of the sensor. The mechanical noise is dominated by Brownian noise (BN), and BN is inversely proportional to the proof mass where silicon is used as the material in most MEMS accelerometers; the physical dimension of the silicon proof mass constrains the minimum level of BN, which is typically in the range from 100 to 1000 microG/Hz1/2. For the reduction of the BN on micro-scale accelerometers, we have employed gold as a material of the proof mass. Owing to the high density of gold, the BN can easily be an order of magnitude smaller than that of silicon proof mass. Moreover, the MEMS sensor can be made by a post-CMOS (complementary metal-oxide semiconductor) process using gold electroplating. The post-CMOS process can also help to shrink the device footprint by implementing the MEMS structures onto the sensing CMOS circuitry. By utilizing the above approaches, the developed MEMS capacitive sensor showed the BN to be less than 1 microG/Hz1/2. The proposed MEMS accelerometers can be of great use to a wide variety of technologies that need to sense micro-motion, and highly-sensitive monitoring of body movements will shed light on the medical and healthcare application.
Hiroyuki Ito
Tokyo Institute of Technology, Japan
Title: Ultra-low power wireless transceiver systems for biomedical application
Time : 10:20-10:40
Biography:
Hiroyuki Ito received a Ph.D. degree in Department of Advanced Applied Electronics, Tokyo Institute of Technology, Yokohama, Japan, in 2006. From 2004 to 2007, he was a research fellow of the Japan Society for the Promotion of Science. He was a temporary visiting researcher and a visiting professor in the Communications Technology Laboratory, Intel Corporation, Hillsboro, OR, USA, in 2006 and 2007, respectively. He was an assistant professor at the Precision and Intelligence Laboratory, Tokyo Institute of Technology, Yokohama, Japan, from 2007 to 2013. From 2008 to 2010, he was with Fujitsu Laboratories Ltd., Yokohama, Japan, where he developed an RF CMOS transceiver and digital calibration techniques for mobile-WiMAX application. Since 2013, he has been an associate professor at the Precision and Intelligence Laboratory, Tokyo Institute of Technology, Yokohama, Japan. His research interests include analog, RF and mixed-signal circuit design for wireless and wireline communications.
Abstract:
The impulse ultra-wideband (I-UWB) RFID technique has been leading short-range wireless communication technology for body area networks (BAN) and biomedical application due to its abilities of high throughput, low power consumption and so on. However, the issue is that the conventional ultra-low power RF (ULPRF) circuits tend to degrade energy-per-bit (E/B) as the bit rate decreases, although BAN has multimodal application and therefore require a variety of bit rate from kb/s to Mb/s. The main reason is that analog circuits consume large steady current which is not proportional to bit rate, and thus they mainly degrade E/B of transceivers at low bit rate. Especially, RF carrier-signal generation is the challenge. Although accurate RF frequency can be achieved by phase locked loop (PLL) technique, its power consumption can be as large as 1 mW. An impulse transmitter (I-TX) can generate RF signal without PLLs by exploiting delay-based impulse generation technique. The drawback of it is that the gate delay varies over ten times in 65 nm CMOS due to large PVT variation under low supply voltage such as 0.5 V. This paper presents design strategies of ULPRF transceiver systems. We also introduce the prototype I-TX in 65 nm CMOS technology to realize energy-per-bit of 1.5 pJ/bit which is better than previous works showed in the semiconductor top conference. Our TX achieves superior energy-per-bit and ultra-low power operation from 1 kb/s to 10 Mb/s. The proposed received signal strength indicator (RSSI) consumes only 89.5 μW with -85 dBm sensitivity. Our ULPRF technology develops unexplored near zero-power region in lower bit-rate wireless communication, which will contribute to realize battery-less wireless communication for biomedical application.
Hector Ricardo Galvan Garcia
Dermatology Hospital, Mexico
Title: Treatment with laser Nd: YAG q-switch vs Ipl in superficial mycoses, deep and atypical mycobacteria
Time : 10:40-11:00
Biography:
Hector Ricardo Galvan Garcia has completed his MD at the age 25 years from Guadalajara University and Postdoctoral studies from Institute of Dermatology of Jalisco. He is Director of Hospital Dermatology Dermoquirurgica in Jalisco, Mexico and he published more 20 papers in reputed journals and serving as an Editorial Board Member of repute.
Abstract:
In this study the effectiveness of laser therapy demonstrated Ny: YAG( 1064 nm / 532 nm) and pulse intensive light on the in vitro treatment of superficial mycoses, deep and atypical mycobacteria was performed in Petri dishes with agar Sabouraud cultures of T. rubrum, M. canis, T. tounsurans, T. mentagrophytes as well and deeper fungi, F. prodrosoi, S. schenki and C. carrioni, also sapphire glass tubes with culture medium lowenstein Jensen for M. abscessus all these luminicas exposing them to these two therapies. Finding in all cases a favorable response in growth of the colonies stopped, varying according to set this type of light, intensity, time and mechanics of it. This has reopened a new horizon in the dermatological therapeutics of the future.
Maria Helena Costa Vieira
Universidade Federal de Mato Grosso do Sul, Brasil
Title: Therapeutic potential of mesenchymal stem cells to treat Achilles tendon injuries
Time : 11:00-11:20
Biography:
Maria Helena Costa Vieira earned her Master in Health and Development in the Midwest from Mato Grosso do Sul University, Campo Grande in 2013. Her Ph.D started this year aiming the effect of stem cell use in tendons in humans. She is currently an assistant professor of medical residency program in Orthopedics and Traumatology, UFMS and medical school.
Abstract:
Rupture of the Achilles tendon diminishes quality of life. The gold-standard therapy is a surgical suture, but this presents complications, including wound formation and inflammation. These complications spurred evaluation of the therapeutic potential of mesenchymal stem cells (MSCs) from adipose tissue. New Zealand rabbits were divided into 6 groups (three treatments with two time points each) evaluated at either 14 or 28 days after surgery: cross section of the Achilles tendon (CSAT); CSAT + Suture; and CSAT + MSC. A comparison between all groups at both time points showed a statistically significant increase in capillaries and in the structural organization of collagen in the healed tendon in the CSAT + Suture and CSAT + MSC groups at the 14-day assessment. Comparison between the two time points within the same group showed a statistically significant decrease in the inflammatory process and an increase in the structural organization of collagen in the CSAT and CSAT + MSC groups. A study of the genomic integrity of the cells suggested a linear correlation between an increase of injuries and culture time. Thus, MSC transplantation is a good alternative for treatment of Achilles tendon ruptures because it may be conducted without surgery and tendon suture and, therefore, has no risk of adverse effects resulting from the surgical wound or inflammation caused by non absorbable sutures. Furthermore, this alternative treatment exhibits a better capacity for wound healing and maintaining the original tendon architecture, depending on the arrangement of the collagen fibers, and has important therapeutic potential.
Armando del RÃo Hernández
Imperial College London, United Kingdom
Title: Switching off the forces that drive pancreatic cancer: Current and Future perspectives molecule in health and disease
Time : 11:35-12:45
Biography:
Armando del Río Hernández obtained his PhD in Chemistry (best thesis award) from the Computense University in Madrid. Following this, he completed a period of postdoctoral training in the US. He worked at Columbia University of New York as a research fellow first, and as a Research Associate, later. He currently leads the Cellular and Molecular Biomechanics group in the Department of Bioengineering at Imperial College London (http://biomechanicalregulation-lab.org). He is a European Research Council fellow and an Editorial Board member of several journals.
Abstract:
Pancreatic cancer is the fourth leading cause of cancer in developed countries with a particularly grim outlook putting the median survival at less than 6 months and the overall 5-year survival rate at only 4%, arguably the worst of all cancers. Unfortunately, despite development of therapies to target specific pathways in cancer cells (in addition to surgical and radiotherapy approaches), there has been little improvement in the outcomes of patients with pancreatic cancer in the last three decades, possibly because an important element of the tumour microenvironment, the abundant stromal reaction or desmoplasia, has been largely ignored, and most studies have focused on the genetics and biochemical signalling in cancer cells themselves. In our lab, we combine cutting edge biophysics and mechanobiology tools to target mechanosensitive pathways in pancreatic stellate cells – the cells responsible for producing this fibrotic reaction in the microenvironment. In this seminar we will discuss the most recent discoveries in the biomechanics of pancreatic cancer.
- Workshop: Creative Approaches for Computational Genomics
Location: Valencia B, Melia Valencia
Session Introduction
Jeffrey Zheng
Yunnan University, China
Title: Creative approaches for computational genomics
Time : 15:55-16:55
Biography:
Jeffrey Zheng has completed his Ph.D in 1994 from Monash University. He is the Professor and Head at the Department of Information Security, School of Software, Yunnan University from 2004. He has published more than 200 papers in national and international conferences, reputed journals and serving as an editorial board member of Information Acquisition. He is active working on exploring mysteries of coding and non-coding DNA/RNA mechanism to use variant logic construction.
Abstract:
Associated with advanced next generation of sequencing technologies to capture various variations on cancers & diseases, huge amount of genomic sequences are ensembled & collected in worldwide databases. There are urgent requirements for modern genomic analysts to apply advanced tools & technologies to index, retrieve, visualize & search genomic sequential information more conveniently. This workshop organizes a group of creative researchers & students together to discuss the state of the arts technologies in addition to exploring new schemes for computational genomics. All levels of approaches are encouraged on the concepts, ideas, models, tools, packages and practices of computational methods for the identification and characterization of functional elements & components from DNA sequence data. The primary target of this workshop is the theory and practice of algorithms in computational genomics, with the goals of using current methods for biological discovery and developing creative algorithms & approaches. This workshop focuses on approaches for extracting and organizing information from similarity aspects on indexing & clustering of protein and DNA sequences through sequence database searches, feature measurements & visualizations. Additional topics include: *Disease sequences: cancer, infectious diseases, cardiovascular disease and psychiatric dysfunctions *Coding & non-coding RNA/DNA sequencing data *Novel ideas & models to identify functional components of genomic variations *Randomness measurements & visualizations *Generation & simulation mechanism on pseudo RNA/DNA sequences *Geometric & topological invariant measurements *Mathematical modelling on variations *Probability & statistical analysis *Combinatorial & permutation models *Efficient computational schemes on clustering genomic sequences *Content-based genomic sequence indexes & retrievals *Integration of genetic and sequence information in genomic databases *Genome browsers and feature visualizations
- Track 10: Systems Biology
Location: Valencia B, Melia Valencia
Chair
Robert A. Drewell
Clark University, USA
Co-Chair
Jacqueline M. Dresch
Clark University, USA
Session Introduction
Robert A. Drewell
Clark University, USA
Title: Decoding the regulatory architecture in Drosophila Hox gene enhancers
Time : 14:00-14:20
Biography:
Robert A. Drewell completed his PhD at Cambridge University in 1999 and conducted postdoctoral studies at University of California, Berkeley and California Institute of Technology. He is an Associate Professor at Clark University and has published more than 30 papers.
Abstract:
In Drosophila, the Abdominal-B homeotic (Hox) gene is expressed in a spatially and temporally restricted pattern along the anterio–posterior axis during embryonic development. The transcription pattern is controlled through specific interactions between transcription factors and a number of enhancers in the neighboring intergenic region. Using computational, mathematical modeling and experimental molecular genetic approaches we investigate how the architecture of transcription factor binding sites mediates the functional activity of these enhancers. A cross-species comparison of the enhancers reveals an evolutionarily conserved signature motif containing two FUSHI-TARAZU activator binding sites that appear to be acting in a cooperative manner. We also find that the transcriptional repressors KNIRPS, KRUPPEL and GIANT are able to restrict gene expression from the enhancers through different molecular mechanisms including short-range repression and competitive binding. Thermodynamic mathematical models can accurately predict the regulatory logic at the enhancers. Our results demonstrate that the transcriptional output of the enhancers relies on a complex set of combinatorial inputs mediated by specific transcription factor binding sites and that the sequence architecture at the enhancers is critical to maintain robust regulatory function.
Jacqueline M. Dresch
Clark University, USA
Title: Detecting nucleotide interdependency in transcription factor binding sites
Time : 14:20-14:40
Biography:
Jacqueline Dresch completed her PhD in Mathematics and Quantitative Biology in 2012 from Michigan State University and postdoctoral studies from Harvey Mudd College in 2013.She is currently an assistant professor in the Mathematics and Computer Science Department at Clark University. She leads an active interdisciplinary undergraduate research group and has published multiple collaborative papers in reputable journals.
Abstract:
A long-standing question in modern molecular biology is how an organism’s genome encodes the instructions for every biological process that takes place throughout their lifetime. In eukaryotes, much of the focus of this field has been on understanding gene expression during development and the binding of protein transcription factors (TFs) to DNA cis-regulatory modules (CRMs) to regulate this expression. Our research focuses on the model organism Drosophila melanogaster. We have explored nucleotide dependencies within binding sites for a group of transcription factors known to be critical to Drosophila development. Our results suggest that many of these proteins have varying levels of nucleotide interdependencies within their DNA recognition sequences, and that, in some cases, models that account for these dependencies greatly outperform traditional models used to predict binding sites.
Bin Zhang
Icahn School of Medicine at Mount Sinai, New York
Title: Comparative network analysis of insulin resistance in caucasian and african americans
Time : 14:40-15:00
Biography:
Bin Zhang is an associate professor of the Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, USA. He holds a Ph.D. and a master degree in Computer Science from the State University of New York at Buffalo, a master degree in electronic engineering from Tsinghua University, China, and a bachelor's degree in electrical engineering from Tongji University, China. His expertise lies in systems biology. He has published 86 peer-reviewed papers including 9 papers in Nature, Science, Cell, Nature Genetics, and PNAS. As of April 2015, his publications have been cited 7131 times.
Abstract:
African Americans (AA) have more pronounced insulin resistance and higher insulin secretion than European Americans (Caucasians or CA) matched on age, gender, and body mass index (BMI). However, molecular mechanisms underlying distinguished insulin resistance in AA remains unknown. In this study, we performed integrative network analysis the gene expression data from the subcutaneous adipose tissue of 99 CA and 37 AA metabolically characterized non-diabetic subjects with a range of insulin sensitivity (SI) and BMI values. We systematically identified the common and ethnicity-specific co-expressed gene modules and drivers. Many adipose co-expression modules were enriched for genes differentially expressed between the two ethnicities or with differential connectivity (MDC) among members of the network module. For example, SIis positive correlated with transcript modules enriched for mitochondrial metabolism in both groups. Several SI associated co-expressed modules are enriched for genes differentially expressed between groups, or had different modular connectivity among members of the network module. SI-associated transcriptional networks that were deranged predominantly in one ethnic group may explain the physiological features of glucose homeostasis among AA subjects. This study paves a way for systematically understanding the molecular mechanisms of insulin resistance in both CAs and AAs. Further studies will be required to identify how genetic and epigenetic factors determine the structure of co-expression networks in adipose tissue that modulate glucose-homeostasis and related physiological traits.
SÃlvia M. Rocha
Universidade de Aveiro, Portugal
Title: Constructing a workflow based on breath and urinary metabolomics to go further on asthma management
Time : 15:00-15:20
Biography:
Sílvia M. Rocha is assistant professor in the Chemistry Department at the Aveiro University. She is BA in Pharmaceutical Sciences at the Pharmacy Faculty (Coimbra University), and PhD in Chemistry (Aveiro University). For the last 22 years, she has performed studies on the characterization of plant-derived natural products, prospection of bioactive compounds, and metabolomics applied to human fluids, plants and microbial systems. Her main skills are oriented to sample preparation and high through-put analysis based on comprehensive two-dimensional gas chromatography and mass spectrometry developments. She published over 85 SCI papers, 2 books, 7 book chapters, and 3 patent applications.
Abstract:
Breath and urinary-based metabolomics are centered on the capture, analysis, and establishment of metabolite biomarker patterns in humans, towards the development of platforms that may be used as tools in a broad spectrum of medical problems. Current developments confirm the potential of this upward trend in the development of rapid, low-cost and non-invasive real-time disease diagnostic tools. Advancements in sampling methodologies and an explosion in the diversity, versatility, and sensitivity of associated detection platforms have catalyzed the interest on the body fluid metabolomics studies. For instance, multidimensional gas chromatography (GC×GC-ToFMS) allowed to go forward on breath and urinary metabolomics towards the understanding asthma perturbations in humans. Asthma is a heterogeneous inflammatory disorder, which is now one of the commonest chronic disorders in the world, and it is also associated with high direct and indirect health costs, especially related with diagnosis and treatment. A particular emphasis in the talk will be placed on the more recent developments on breath and urinary asthma metabolomics towards disease management (diagnosis, disease status evaluation, follow-up therapy and personalized disease evaluation). Challenges associated with metabolomic workflow construction, namely those related to the complexity of biological samples, data acquisition and processing from high throughput techniques (NMR and multidimensional gas chromatography), and search for associations between the instrumental data and metabolic pathways or clinical parameters will be also discussed. Acknowledgments: Funding is acknowledged from the FEDER through the COMPETE Programme and from the FCT, Portugal, under projects PEst-C/QUI/UI0062/2013 (Research Unit 62/94 QOPNA), and PTDC/QUI-QUI/117803/2010.
Samara Silva de Souza
Federal University of Santa Catarina, Brazil
Title: Systems Biology of nanocellulose synthesis: new approach to build a core metabolic model based on computational analysis
Time : 15:20-15:40
Biography:
Samara Silva de Souza is currently a PhD student and researcher at the Chemical Engineering Department of the Federal University of Santa Catarina. Her research interests include Genomics and Bioinformatics and Systems Biology. The Integrated Technologies Laboratory's - InteLab major goal is to integrate multidisciplinary researches, particularly those that unify molecular biology and chemical engineering interests. The InteLab works in the fields of Genome Engineering (Bioinformatics, Metabolic Engineering, and Applied Genomics) and Chemical and Biological Reactors, aiming to develop innovative processes and products for chemical, biotechnological and medical applications. Her thesis concentrated on the study of metabolic network reconstructions, in particular, a bacterium which has been used for nanocellulose biosynthesis. The importance of nanocellulose-based is particularly for tissue engineering applications. Through these researches she acquired different skills in the area of Systems biology and acquainted with different tools and analysis.
Abstract:
Systems biology is a new field that aims to focus on molecular components to understand biological systems. The systematic approach to biology is not new, but it has recently gained new attraction due to emerging experimental and computational methods. Reconstruction of genome-scale metabolic models based on a combination of genome sequence and biochemical information have influenced the field of systems biology in the past decade. Different approaches are frequently used to identify the components of the system and their interactions, to build in silico models that explain complex cellular processes and make testable predictions, as well as to represent these relationships using different computational resources. The Gram-negative bacterium Gluconacetobacter hansenii has been extensively used for nanocellulose synthesis and the recent availability of its genome sequence allows the development of metabolic models of the production of bacterial nanocellulose by integrating typical experimental work with genomic and high-throughput post-genome data. However, despite the importance of bacterial cellulose-based biomaterials particularly for tissue engineering applications, a core metabolic model of its biosynthesis has not been proposed so far. The constraint-based reconstruction and flux analysis approach was used to analyze the model and simulate different conditions to evaluate its consistency and representativity for cellulose biosynthesis. The reconstruction process involves the following steps: 1) creation of a draft model using automated resources, 2) manual curation to construct the core model, 3) conversion of the model into a mathematical format and, 4) biological and biochemical analysis of the network. A core metabolic model developed can provide strategies for developing these biomaterials through a better knowledge of G. hansenii metabolic pathways and elevate our capability for understanding the metabolic capacity under perturbations such as environmental changes.
Nabil Semmar
Institut Supérieur des Sciences Biologiques Appliquées de Tunis, Tunisia
Title: A new computational approach to graphically highlight regulation relationships in metabolic systems from chromatographic data
Time : 15:40-16:00
Biography:
Nabil Semmar is specialized in computational biology focusing his scientific researches on analysis of regulation laws of structural diversity and functional variability in biosystems. He is a multidisciplinary biologist with a long academic itinerary including Master’s in Environmental Sciences (marine and terrestrial), a PhD in Phytochemistry and Post-doctoral researches in Pharmacometrics and Pharmacokinetic Modeling (1988-2004). In his PhD (Lyon, 2000), he developed an original simplex approach helping to statistically highlight multidirectional (flexible) relationships between biological components of polymorphic systems. His finding concerning simplex control of complex biosystems was appreciated by IAEA who invited him as consultant and speaker for conference in scientific program on plant and animal resources management (Vienna, 2008). More recently, he showed the ability of simplex approach to extract hysteretic regulation laws between drug metabolites in pharmacokinetic populations (2010). Moreover, his statistical contributions in pharmacometrics and population pharmacokinetics modeling were appreciated by Biomedical Simulations Resource Group (California) who invited him as speaker for a conference (Los Angeles, 2007). In pedagogy, he is the author of three books on statistics, computational metabolomics and chemotaxonomy in addition to several book chapters published in different international publishers (since 2009). He is Associate Professor at the University of Tunis (ISSBAT) (Tunisia) where he teaches these fundamental and specialization fields in different licenses and masters of biological sciences.
Abstract:
A new computational approach was developed to highlight some metabolic order by statistically exploring the variability between and within chromatographic profiles representing different states in the studied population. The approach consisted in combining metabolic variability of chromatographic profiles initially classified into metabolic trends (MbTrs). Illustration was based on 248 profiles of plasmatic L-dopa and its metabolites (3-OMD, DOPAC and HVA) analysed at different times (after L-dopa administration) in 34 patients suffering from Parkinson disease. After statistical classification of the population into different MbTrs, classified profiles were iteratively combined in silico by applying a Scheffé’s mixture design. To take into account the variability within and between MbTrs, the mixture design was iterated k times by bootstrap leading to k response matrices that were averaged to obtain a complete set of smoothed profiles representing gradual regulations between metabolites. Smoothed response data were used to graphically analyse backbone of the metabolic system. The results highlighted MbTr-dependent relationships between metabolites, revealing high metabolic flexibility. Apart from this static application, the same iterative algorithm was applied to separate data subsets corresponding to different sampling times. From 3-D plots (time t, metabolite x, metabolite y), smoothed results highlighted a counter-clock hysteresis between a precursor (DOPAC) and its derivative (HVA) suggesting a lag between metabolic regulations; such a process was compatible with the metabolic pathways.