Day 2 :
Keynote Forum
Hamid Mirzaei
UT Southwestern Medical Center, USA
Keynote: Hydralazine induces stress resistance and extends C. elegans lifespan by activating the NRF2/SKN-1 signaling pathway
Time : 09:00-09:40
Biography:
Hamid Mirzaei research is focused on finding the target of novel and FDA approved compounds using a combination of proteomics, computational biology, and biochemistry. Many FDA approved drugs are currently in use without a clear understanding of their mechanism of action. On the other hand, there are quite a few well-characterized natural products with unknown targets. He uses systems biology to understand the drug’s mechanism of action by identifying the target of the drugs and their cellular and organismal phenotypes.
Abstract:
Advances in modern medicine have led to increased life expectancy. As the aging population increases, finding a cure for the age-related cognitive decline is becoming more and more important. A hallmark of neurodegenerative diseases, one of the main pathologies underlying age-related dementia, is the deposition of insoluble proteins in cells of the neuromuscular system causing proteotoxicity. Substantial literature suggests that the primary inducer of proteotoxicity in aging is chronic deterioration of defense machinery including antioxidant, heat shock, and degradation systems. Deterioration of defense machinery create imbalances in aggregation and clearance pathways leading to proteotoxicity by altering aggregate dynamics, localization and aberrant interactions. One of the main targets of toxic proteins aggregates is mitochondria resulting in mitochondrial dysfunction and increased oxidative stress. Nuclear factor (erythroid-derived 2)-like 2 and its Caenorhabditis elegans ortholog, SKN-1, are transcription factors that have a pivotal role in the oxidative stress response, cellular homeostasis, and organismal lifespan. Similar to other defense systems, the NRF2-mediated stress response is compromised in aging and neurodegenerative diseases. Here, we report that the FDA approved drug hydralazine is a bona fide activator of the NRF2/SKN-1 signaling pathway. We demonstrate that hydralazine extends healthy lifespan (~25%) in wild-type and tauopathy model C. elegans at least as effective as other anti-aging compounds, such as curcumin and metformin. We show that hydralazine-mediated lifespan extension is SKN-1 dependent, with a mechanism most likely mimicking calorie restriction. Using both in vitro and in vivo models, we demonstrate that hydralazine has neuroprotective properties against endogenous and exogenous stressors. Our data suggest that hydralazine may be a viable candidate for the treatment of age-related disorders
Keynote Forum
Suzanne Scarlata
Worcester Polytechnic Institute, USA
Keynote: Regulation of the activity of the promoter of RNA-induced Silencing, C3PO
Time : 09:40-10:20
Biography:
Suzanne Scarlata is a Professor Emeritus of Stony Brook University and a Whitcomb Chair at Worcester Polytechnic Institute. Most of her research has focused on the regulation of G protein signaling in model systems and in cultured cells using primarily fluorescence methods. The work presented here represents an unexpected connection between the impact of extrasensory information and post-transcriptional gene regulation through the Gαq/phospholipase Cβ signaling pathway.
Abstract:
RNA-induced silencing is a process which allows cells to regulate the synthesis of specific proteins. RNA silencing is promoted by the protein C3PO (component 3 of RISC). We have previously found that phospholipase Cβ, which increases intracellular calcium levels in response to specific G protein signals, inhibits C3PO activity towards certain genes. Understanding the parameters that control C3PO activity and which genes are impacted by G protein activation would help predict, which genes are more vulnerable to down-regulation? Here, using a library of 1018 oligonucleotides, we show that C3PO binds oligonucleotides with structural specificity but little sequence specificity. Alternately, the rate of hydrolysis is exquisitely sensitive to the substrate stability. Importantly, we find that oligonucleotides with higher Tm values are inhibited by bound PLCβ. This finding is supported by microarray analysis in cells over-expressing PLCβ1. Taken together our work enables predictions of the genes whose post-transcriptional regulation is responsive to the G protein/phospholipase Cβ/calcium signaling pathway.
Keynote Forum
Tofik Murtuza Nagiev
Nagiev Institute of Catalysis and Inorganic Chemistry, Azerbaijan
Keynote: The macroscopic coherence in synchronized chemical and biochemical reactions: The way to the self-organizing chemical systems
Time : 10:40-11:20
Biography:
Tofik Nagiev is a vice-president of Azerbaijan National Academy of Sciences, Director of Research Center of Azerbaijan National Encyclopedia and Department chief of Nagiev Institute of Catalysis and inorganic chemistry of ANAS. The professor of the department of the physical and colloid chemistry of Baku State University.
Abstract:
Chemistry is on the brink of establishing the self-organizing chemical systems where algorithms, allowing a group of various chemical reactions to combine in an ensemble in order to obtain the final product in a single reaction medium with high selectivity in a short time, are implemented. The synthesis of a target biochemical product in the living organisms at the cellular level is carried out practically in no time, and this is possible only in conditions of the coherent synchronized reactions, which represent the ensemble of the chemical reactions at the cellular level. Unfortunately, these reactions haven’t been practically implemented in the chemistry as a model system, probably due to the lack of the adequate theories explaining working principles of enzyme ensembles (unlike the working principles of individual enzymes). Developed macroscopic theory of coherent synchronized chemical reactions has been adequately corroborated by experimental studies. Here we propose an experimentally corroborated model of coherent synchronized reactions and its mathematical apparatus, consisting of the determinant equation and coherent correlation. Thus, self-organization of an ensemble of reactions capable of being intensified and weakened simultaneously and, therefore, inducing macroscopic coherence, may be suggested as the basis for the principle by which many enzymatic ensembles are organized.
Keynote Forum
Makoto Ubukata
Hokkaido University, Japan
Keynote: The Logic of bioactive small molecules: Looking for new drugs for refractory diseases
Time : 11:20-12:00
Biography:
Professor Ubukata earned a PhD from Hokkaido University in 1980. After postdoctoral fellowships at Indiana University and RIKEN, he became Scientist at RIKEN in 1984. He was appointed a Professor of Biotechnology Research Center, Toyama Prefectural University in 1995. In 2003, he moved to Sapporo as a Professor of Department of Agriculture, Hokkaido University. He is the recipient of JSBBA Award for Young Scientist (1989), Sumiki-Umezawa Memorial Award (1995), Japan Prize of Agricultural Science (2017), and The Yomiuri Award of Agricultural Science (2017). He has been Professor Emeritus since 2015 and JSBBA fellow since 2016. His current research interest includes the study on structure and function of the biologically active small molecule, which might save directly or indirectly a number of people.
Abstract:
In this Congress, I will outline my way of thinking about biologically active small molecules. We discovered many biologically active small molecules. Ascamycin was Xanthomonus specific antibiotic, cationomycin was a polyether ionophore antibiotic, liposidomycin B was an inhibitor of peptidoglycan biosynthesis, tautomycin and tautomycetin were later put into practical use as biochemical reagents. Reveromycin A also was utilized as a biochemical reagent and a candidate drug for osteoporosis, epiderstatin was discovered as a glutarimide antibiotic, (+)-indocarbazostatin and (–)-indocarbazostatin B are inducers of neulite outgrowth in PC12 cells, (+)-epogymnolactam was discovered as an autophagy inducer isolated from Gymnopus sp. The rediscovery of mycophenolic acid as a latent agonist of PPARg led to the development of many interesting inhibitors against HDAC, human IMPDH, and T. congolense IMPDH. The study of TcIMPDH led to the identification of TcGMPR. We recently discovered an existing drug as a potential therapeutic agent for immunodeficient model mouse infected with Cryptosporidium parvum via newly developed high-throughput screening for CpIMPDH inhibitors. A biologically active small molecule may save directly or indirectly a number of people. Even if the molecule has not been used as a therapeutic agent, it can be used as a useful chemical probe for dissecting a living cell into different biochemical pieces. Such biologically active small molecules derived from microorganisms have been primarily found in cultivable microorganisms that make up only 1% of total microbes in nature. If you can cultivate previously uncultured microorganisms that accounting for the other 99% of microorganisms, the possibility to discover new biologically active small molecules will expand. We discovered zinc methylphyrin, zinc coproporphyrin, and coproporphyrin as novel growth factors for uncultured Leucobacter sp. These findings may provide a general strategy for discovering further biochemical reagents, antibiotics, and therapeutic agents for the treatment of refractory diseases.
- Systems and Synthetic Biology | Pharmaceutical Biochemistry | Biochemistry and Enzymology | Computational Systems Biology | Cellular and Molecular Biology | Biophysics
Location: Colombard
Chair
Hamid Mirzaei
UT Southwestern Medical Center, USA
Co-Chair
Dagmar Heinová
University of Veterinary Medicine and Pharmacy in Košice, Slovak Republic
Session Introduction
Orkid Coskuner-Weber
Turkısh-German University, Turkey
Title: Mitochondrial dysfunction, oxidative stress and genetic factors in Alzheimer´s disease
Time : 12:00-12:30
Biography:
Orkid Coskuner-Weber is an expert in Alzheimer´s and Parkinson´s disease mechanism studies and monoclonal antibody design. She recived her Ph.D. degree from the Universitaet zu Koeln in Germany. She was a postdoc at Johns Hopkins and Stanford Universities. She was an assistant professor at George Mason University and at the University of Texas at San Antonio. She recently took a position in Istanbul for opening the Alzheimer´s and Parkinson´s disease research center. She has been associated with the National Institute of Standards and Technology since 2005. She develops and uses quantum chemical, statistical mechanical, bioinformatics, artificial intelligence and experimental tools in her research activities.
Abstract:
Alzheimer`s disease affects 10 million Americans and 44 million people worldwide. There are various biochemical mechanisms and processes that play a role in Alzheimer´s disease. These mechanisms are debated in the literature and there is currently no efficient drug that halts the progress of the disease. Efficient and effective drug design studies require detailed understanding of associated biochemical and biophysical mechanisms at the atomic level with dynamics. We investigate all biochemical processes and mechanisms associated with Alzheimer´s disease using quantum chemistry, statistical mechanics, bioinformatics, artificial intelligence and experiments. Using the information that we gain from biochemical investigations, we design monoclonal antibodies in collaboration with pharmaceutical companies. In this talk, we will present some of our studies about the roles of genetics, mitochondrial dysfunction and oxidative stress mechanisms in Alzheimer´s disease. Our theoretical and experimental results show that ATP reduces the fibrillization of disordered amyloid-β, transition metal ion coordination with amyloid-β increases the fibrillization progress and genetic factors significantly impact the fibrillization and aggregation properties of amyloid-β alloforms. Furthermore, we will provide insights into monoclonal antibody design for the treatment of Alzheimer´s disease.
Mehmet Gokhan Gokcen
Turkish-German University, Turkey Panel
Title: Impact of NAc on the glycosidic linkage flexibility of carbohydrate-peptide complexes
Time : 12:30-13:00
Biography:
Mehmet Gokhan Gokcen has completed his undergraduate, graduate and PhD degrees from Bogazici University Department of Mechanical Engineering. Since September 2017, he has been working as Assistant Professor in the Department of Mechanical Engineering at Turkish-German University. His expertise is in numerical simulation of physical systems, especially finite element analysis and computational fluid dynamics. He is currently investigating the role of glycolysis in Alzheimer's and Parkinson's disease using density functional theory and classical mechanics approaches. He is contributing to the research on the effects of genetics and on the mechanisms of oxidative stress and mitochondrial dysfunction in Alzheimer's and Parkinson's diseases.
Abstract:
A simple approach to exploring the impact of glycosylation on the conformation and biological activity of proteins is to investigate model glycopeptide species with one single monosaccharide moiety attached to amino acids. The goal originates in the experimental observation that truncation of the oligosaccharides antennae of glycoproteins does not yield dramatic conformational and immunological changes, as opposed to the removal of the first glycan moiety. In the course of evolution, prokaryotic organisms developed a considerable diversity in the supramolecular architecture of their multi-layered cell boundaries. One of the most commonly observed bacterial cell surface structures is two-dimensional arrays of proteinaceous subunits termed S-layers. They represent almost universal features on archaebacteria cell envelopes and were already detected in hundreds of different species of nearly every taxonomic group of walled eubacteria. S-layer like structures have also been observed in bacterial sheaths and on the surface of cell wall eukaryotic algae. Since S-layers are found in Gram-positive and Gram-negative eubacteria and archaebacteria they can be associated with quite a different cell envelope structures such as peptidoglycans (glucose-serine complexes). In fact, chemical analyses and genetic studies of S-layers of a variety of eubacteria revealed that composed of a protein or glycoprotein species. The glycosidic linkage flexibilities of glucopyranose-serine species in aqueous solution are difficult to investigate using conventional tools due to their high flexibility and solvent effects. Quantum chemical techniques provide a solution for these studies. We present here the structural and energetic properties of glucose-serine complexes in water and the impact of NAc on the structural and energetic properties of glucose-serine using first-principles calculations.
Oladepo Mutiu Lolade
Adekunle Ajasin University, Nigeria
Title: Effect of saponin from Solanum anguivi on heart function of Alloxan induced Diabetic rats
Time : 14:00-14:30
Biography:
Oladepo Mutiu Lolade is currently studying for his Master’s degree at Department of Biochemistry, Adekunle Ajasin University, where he bagged his Bachelor’s degree. He is a fully baked, technically inclined, scientifically unbiased and self-motivated researcher with a good laboratory proficiency. He is presently a Scientific Officer at General Hospital Akure Ondo State, Nigeria. He is a competent and enthusiastic researcher with interest in Nutrition and Cardiovascular Diseases. His keen interest understanding the contribution of African diet and nutrition to cardiovascular health has driven him into various research that make use of experimental animal models to investigate the effects of commonly consumed Nigerian foods on markers of cardiovascular health
Abstract:
Solanum anguivi is a semi-domestic indigenous vegetable very valuable in many African countries with potential to become a cultivated market vegetable in Nigeria. Uptake of Solanum anguivi cause hypoglycemic effect, hypertension etc. The effect of Saponin from Solanum anguivi on heart function of the alloxan-induced diabetic rat was investigated in this study. Twenty four (24) rats of average weight 120g were randomly divided into six (6) groups A-F. Group A (control) rats were given 2.0ml of distilled water, Group B (Diabetic control), Group C to F were diabetic rats which were administered 20mg/kg, 40mg/kg and 80mg/kg Saponin from Solanum anguivi respectively for 14 days. The results showed that there was a significant reduction in plasma glucose in the diabetic rat to almost the level in the control. The result also shows that there were a significant reduction in Aspartate Aminotransferase (AST) and Alanine aminotransferase (ALT) activities in serum and heart compared with the control (p<0.05). This study shows that Solanum anguivi fruit has an anti-diabetic effect on alloxan induced diabetic rat.
Harun Pirim
King Fahd University of Petroleum and Minerals, Saudi Arabia
Title: Descriptive and predictive analysis of gene co-expression networks
Time : 14:30-15:00
Biography:
Harun Pirim received his PhD degree in Industrial and Systems Engineering (ISE) from Mississippi State University in May 2011. Harun worked on microarray data analysis in collaboration with Computer Science and Forestry departments. His research interests include mathematical programming and heuristic applications in biology, sociology, and supply chain fields focusing mainly on graph mining. He has several papers published in Computers and Operations Research, Computers in Biology and Medicine, conference proceedings, book chapters and a brief Springer book on supply chain optimization.
Abstract:
Ample availability of gene co-expression data challenges researchers to find and apply unique approaches for extracting biological information to infer about gene functions or predict gene-disease relations. By means of reliable co-expression network construction techniques compiled networks exist and they require further predictive analysis to focus on the genes or groups of the genes exhibiting certain patterns reflected on the co-expression networks. We propose an integrated network analysis where social network descriptive analysis techniques are borrowed to summarize some structural features of the network. Then, the features are employed in optimization models to find groups of genes exhibiting certain patterns