12^th International Conference on STRUCTURAL AND MOLECULAR BIOLOGY May 14-15, 2018 Osaka, Japan

Biography:

Xiongwu Wu has his expertise in molecular simulation and method development. He developed Self-Guided Molecular/Langevin Dynamics simulation (SGMD/SGLD) methods that enable molecular simulation to access long-time scale events. He has developed core-weighted grid-threading method for rigid fitting of proteins into low resolution cryo-EM maps and Map-restrained SGLD (MapSGLD) method to flexible fit protein structures into cryo-EM maps. He is also the developer for both molecular simulation and modeling packages AMBER and CHARMM

Abstract:

Kinesins are motor proteins that move unidirectionally along microtubules as they hydrolyze ATP. Although the general features of the kinesin walking mechanism are becoming increasingly clear, some key questions remain unanswered, such as how they convert the chemical energy of ATP into mechanical energy and walk processively. In this study, through molecular simulations and free energy calculations, we found that in aqueous solution, kinesin favors an extended form with its microtubule-binding interface (MTBI) motif unfolded, as seen in a recent X-ray structure of kinesin-8. Through the flexible fitting of two newly released cryo-electron microscopy (cryo-EM) maps, we derived atomic structures of the kinesin dimer-microtubule complexes in both two-head-bound and one-head bound states. Free energy calculations showed that kinesin bound to microtubules has a lower free energy than the extended form and that the free energy difference is in the range of the free energy released by ATP hydrolysis. The transition between the extended and compact forms, the structural differences of the leading and trailing heads and atomic force simulations lead us to a completely new mechanism by which kinesin dimers walk on microtubules.

Biography:

Wolfgang Fischer is a Professor at the Institute of Biophotonics, School of Biomedical Science and Engineering, National Yang-Ming University, Taiwan. He has obtained his PhD in Chemistry at Heidelberg University, Germany, working in the field of vibrational spectroscopy in 1991. He has worked for years in USA like in Boston University as Postdoctoral Fellow working on bacteriorhodopsin using vibrational spectroscopy; Germany in Analytical Chemistry, working on ion channels as potential biosensors; Oxford University as EU Marie Curie Research Fellow and later as Lecturer, working on viral ion channels using bilayer recordings and molecular dynamics simulations and later moved to Taiwan. His field of research is on biophysical aspects describing dynamics and energetic of protein-protein interactions (PPIs) of membrane proteins. The focus is on the development of computational platform technologies to support structural modeling for drug discovery and design as well as for materials sciences.

Abstract:

Computational methods comprise a valuable tool to close the sequence-structure gap, especially for membrane proteins. At this stage, secondary structure prediction programs are available to identify putative stretches of helical transmembrane domains (TMDs) while few programs are developed to predict a beta sheet fold as the membrane spanning motif. With the knowledge about the putative TMDs, here adopting a helical motif, at hand these TMDs can be assembled into a tertiary structure and finally into putative quaternary structures using docking approaches. As a test case, viral channel forming proteins (VCPs), sometimes also called viroporins, are used to develop strategies to generate plausible structures. VCPs are about five time smaller than human ion channels and therefore used as a miniaturized system to investigate how ion channels are formed. Using E5 protein of human papilloma virus type 16 (HPV-16), the assembly of a polytopic membrane protein with three TMDs is presented in its hexameric form. Using a docking approach, the monomeric form is generated first before assembling into the hexamer. The quality of the model is assessed using potential of mean force calculations (PMF) identifying weak ion selectivity. Principle component analysis (PCA) of the data from a classical molecular dynamics simulation reveal asymmetric dynamics of the monomers. These dynamics are compared with those derived for other VCPs such as polytopic p7 of hepatitis C virus (HCV) with two TMDs and bitopic M2 of influenza A. Finally, coarse grained simulations are applied to probe the formation of the quaternary structure of e.g., Vpu of HIV-1.

Biography:

Anil Batta is presently an Associate Professor and Senior Consultant in Govt. Medical College, Amritsar, Punjab, India. He has received his MBBS and MD in Medical Biochemistry from Govt. Medical College, Patiala in 1984 and 1991, respectively. His research interest is mainly in clinical application especially cancer and drug de-addiction. He has supervised more than 15 MD, MSc and Doctorate researches and published more than 30 international research papers. He is the Chief-Editor of America’s Journal of Biochemistry. He is also working as an Advisor to the Editorial Board of International Journal of Biological and Medical Research. He is also a Deputed Advisor to Pakistan Medical Journal of Biochemistry. He has been attached as Technical Advisor to various national and international conferences in Biochemistry, also with hi-tech endocrinal, genetics and automated labs of GGS Medical College, Faridkot.

Abstract:

Aim: It is known that in patients with Diabetic Foot Syndrome severe forms of mental disadaptation are observed. They are manifested psycho-emotional disorders and poor treatment compliance. The aim of this work was to study the forms of mental disadaptation in patients with Diabetic Foot Syndrome and the role of psychological and somatic factors in their development.

Method: The following parameters: Levels of anxiety and depression, alexithymia, irrational cognitive principles, personality profile, severity of somatic disorders and treatment compliance were studied in 120 Diabetic Foot Syndrome patients.

Result: The study revealed two main groups of patients with various forms of mental disadaptation and some relationship of psycho-emotional and somatic disorders. In the first patient’s group with severe form mental disadaptation, there were observed high level of alexithymia, depression, the prevalence of psychopathic personality types, combined with deep encephalopathy, cognitive disorders and long duration of disease. A poor compliance of treatment, the progressive deterioration of the disease, large number of lower limb amputations was observed also in this group of patients. In the second patients’ group with less severe form of mental disadaptation, there were observed small level of alexithymia, high anxiety and the prevalence of neurotic personality types and a shorter duration of disease. A good treatment compliance and smaller number of lower limb amputation was also observed in this group of patients.

Biography:

Whitney Yin is an Assistant Professor for University of Texas Medical Branch, USA. She has received Doctoral degree (PhD) in Department of Pharmacology and Toxicology. She is the Editorial Board Member of many peer reviewed journals and has many publications in national and international journals to her credit. She is committed to highest standards of excellence and it proves through her authorship of many books.

Abstract:

Like all high-fidelity DNA polymerases, human mitochondrial DNA polymerase, Pol-g contains polymerization (pol) activity for DNA synthesis and proofreading exonuclease (exo) activity for error correction. Pol-g is a holoenzyme consists of a catalytic subunit Pol-gA and accessory subunit Pol-gB. Pol-gA contains all enzymatic activity including pol, exo and deoxyribose phosphate (dRP) lyase, Pol-gB contains no enzymatic activity of its own but regulates all Pol-gA activates, consequently, the holoenzyme has higher processive and elevated dRP lyase activity. We determined crystal structures of Pol-g ternary complex with primer/template DNA and an incoming nucleotide to understand how the two active sites communicate with each other. The ternary complex reveals a b-hairpin situated between the two active sites in Pol-gA could transfer the information of nucleotide misincorporation in the pol site to the exo site 40Å away for excision. Our enzymatic studies indicate that Pol-g variants in the b-hairpin completely abolish pol activity while retains full exo activity. Additionally, we performed molecular simulation and found the hairpin region are energetically destabilized with perturbation of Pol-g variants in either pol or exo active sites, revealing for the first time that the two active sites are energetically coupled and DNA strand shuttling is accompanied by destabilization of the path connecting the pol and exo sites.

Biography:

Joel I Osorio is the CEO and Founder of Biotechnology and Regenerative Medicine at RegenerAge International™. He is the Vice President of International Clinical Development for Bioquark, Inc. and Chief Clinical Officer at ReAnima™ Advanced Biosciences. He is an Advance Fellow by the American Board of Anti-Aging and Regenerative Medicine (A4M), Visiting Scholar at University of North Carolina at Chapel Hill (Dermatology) and Fellow in Stem Cell Medicine by the American Academy of Anti-Aging Medicine and University of South Florida.

Abstract:

As it has been previously demonstrated that coelectroporation of Xenopus laevis frog oocytes with normal cells and cancerous cell lines induces the expression of pluripotency markers and in experimental murine model studies, mRNA extract (Bioquantine®) purified from intra and extra-oocyte liquid phases of electroporated oocytes showed potential as a treatment for a wide range of conditions, including Spinal Cord Injury (SCI) among others. The current study observed beneficial changes with Bioquantine® administration in a patient with a severe SCI. Pluripotent stem cells have therapeutic and regenerative potential in clinical situations CNS disorders even cancer. One method of reprogramming somatic cells into pluripotent stem cells is to expose them to extracts prepared from Xenopus laevis oocytes. The positive human findings for spinal cord injury with the results from previous animal studies with experimental models of traumatic brain injury and SCI respectively as our evidence and due to ethical reasons, legal restrictions and a limited number of patients, we were able to treat only a very small number of patients, deciding to include in our protocol the RestoreSensor SureScan to complete it. Based on the electrical stimulation for rehabilitation and regeneration after spinal cord injury published by Hamid and MacEwan, we designed an improved delivery method for the in situ application of MSCs and Bioquantine® in combination with the RestoreSensor® SureScan®. To the present day the patient who suffered a complete section of spinal cord at T12-L1 shows an improvement in sensitivity, strength in striated muscle and smooth muscle connection, 13 months after the first treatment and 6 months after the placement of RestoreSensor® at the level of the lesion, showing an evident improvement on his therapy of physical rehabilitation (legs movement) on crawling forward and backwards and standing on his feet for the first time and showing a progressively important functionality on both limbs.

Biography:

Lisa M Domke is currently a PhD student in the Helmholtz Group for Cell Biology of Professor Werner W Franke at German Cancer Research Center, Germany. She has prepared her Master’s thesis with one of the pioneers in cancer research, Professor Dr. Robert A Weinberg at the Massachusetts Institute of Technology (MIT) in Cambridge, USA. The nature of her degree in Biotechnology has allowed her to learn various analytical as well as light and electron microscopical techniques and to work in different fields of life sciences.

Abstract:

Mature seminiferous tubules (STs) of mammalian testes comprise the Sertoli cells and germ cells and are tightly surrounded by a special peritubular cell wall. Using biochemical, immunocytochemical and electron microscopical methods, we have determined that STs differ from all other epithelia by the absence of cytokeratin intermediate filaments (IFs) but are rich in vimentin IFs, do not contain major epithelial marker structures and molecules such as desmosomes or E-cadherin-based adherens junctions (AJs) but contain exclusively N-cadherin-based AJs. In Sertoli cells, we have found two new junction structures: (1) N-cadherin-based areae adhaerentes which often represent even very large areas connecting Sertoli cells with each other or with germ cells. (2) Special AJs arranged in closely and regularly spaced rows of tight junction-like structures and associated with 5-8 nm wide cytoplasm-to-cytoplasm channels (cribelliform junctions). The seminiferous tubule cells are attached to the peritubular wall by a well-developed basal lamina but lack hemidesmosomes and hemidesmosomal marker molecules. The peritubular wall is a stack system of layers of extracellular matrix (ECM) structures alternating with monolayers of very flat lamellar smooth muscle cells (LSMCs). These LSMCs represent differentiated smooth muscle cells (SMCs; positive for smooth muscle α-actin, the corresponding myosin light and heavy chains, α-actinin, tropomyosin, smoothelin, desmin, vimentin, filamin, talin, dystrophin, caldesmon, calponin and protein SM22α). The cells are laterally connected often in overlapping protrusions by AJs containing cadherin-11 as the predominant cadherin, and also P-cadherin and rarely N-cadherin, anchored in cytoplasmic plaques containing β-catenin, proteins p120 and p0071, plakoglobin and protein myozap. LSMCs also contain typical SMC structures such as dense bodies, plasma membrane-associated focal adhesions and caveolae. Thus, we conclude that these LSMCs represent a specific SMC type and not just myoid cells or myofibroblasts as stated in the literature.

Biography:

Jacob Anderson C Sanchez is a Faculty/Researcher of the Pampanga State Agricultural University. His main objective is to conduct researches related to the development of Aglibut sweet tamarind using molecular biology techniques. He is passionate in conducting researches that are essential in ensuring the profit of the marginalized sector. He has also presented his various researches in international conferences at Singapore, Japan, and France.

Abstract:

Aglibut sweet tamarind is a priority commodity of the Pampanga State Agricultural University (PSAU). However, this variety looks like sour tamarind especially when they are still seedlings. This may result in potential economic loss for farmers or business capitalists who would venture in this lucrative business. Therefore, this study aimed to obtain their molecular identification using cpDNA (rbcL, matK) and nrDNA (ITS) markers; to determine the relationships of the samples using Maximum Likelihood and Maximum Parsimony Cladograms and to evaluate the universality of ITS, rbcL and matK in tamarind. BLAST results showed that majority of the samples belong to Tamarindus indica with 99-100% homology. Maximum Parsimony (MP) and Maximum Likelihood (ML) for matK showed that Aglibut sweet tamarind formed a monophyletic group with PSAU’s sour tamarind and paraphyletic to wild-type sour tamarind obtained from Lubao, Pampanga. On the other hand, MP and ML for ITS did not show a fully resolved tree. For the universality, results showed that matK had 100% PCR and sequencing success rates. Meanwhile, ITS showed 100% PCR success rate and 83% sequencing success, whereas rbcL did not work well for the samples. Hence, we conclude that DNA barcodes matK and ITS are the genetic markers that can be used for molecular identification of Aglibut and sour tamarind samples. More importantly, we report that Aglibut sweet tamarind has closer genetic relationship with the PSAU sour tamarind than other varieties

Biography:

Chantal Prévost is a Researcher at the Theoretical Biochemistry Laboratory (LBT) of the French National Research Center (CNRS), in Paris. She has developed a strong expertise in studying complex biological processes in silico via the integrative exploration of unstable macromolecular self-assembly substates. She has elaborated new algorithms for flexible macromolecular docking and protein fiber modeling. She presently applies this expertise to tackling the mechanism of homologous recombination as well as exploring the architecture of oligomeric assemblies, in collaboration with the Prentiss team in Harvard University, USA

Abstract:

Homologous recombination (HR) is an essential biological process common to all living cells that maintains the genome integrity by faithfully repairing double-strand breaks (DSBs). The HR process searches the genome for a region that is homologous to the broken DNA and uses this region as a template to restore the DNA integrity, via the capture of the complementary strand that gets paired with the damaged DNA. Nucleofilaments resulting from the polymerization of a recombinase (RecA in prokaryotes) on each damaged DNA strand recruit the genomic DNA, test it for homology and promote strand exchange. The coordination of dynamic stages with different time and length scales enables the process to be simultaneously fast and stringent. By combining docking explorations and molecular dynamics simulations at the atomic level, we have integrated the results from 30 years studies into new structural insights on the HR process. We propose a mechanism for the initial recognition/strand exchange phase, where more than 80% of non-homologous sequences are eliminated, that uses mechanical tension in the DNA to locally destabilize the base pairing interactions in the searched DNA and perform swift homology tests via pairing exchange. We also investigated the role of ATP hydrolysis in the slower phases of HR using molecular dynamics simulations. These simulations, based on the hypothesis that the filament can change the internal arrangement of its monomers upon ATP hydrolysis, revealed how hydrolysis may promote reverse strand exchange in the filament. This provides a structural interpretation to the observed destabilization of the strand exchange product within filaments where ATP is hydrolyzed.

Biography:

Nibedita Naha has her expertise in molecular approach of reproductive toxicology and neurotoxicology, cell signaling and RNA interference using animal models and human subjects with respect to occupational exposure. She has a passion in improving the health and wellbeing through her research findings in the respective fields since 2000. She is the recognized PhD Guide and Reviewer and Editorial Member of several international and national peer-reviewed journals. She is also the CPCSEA nominee for monitoring animal experiments in several research organizations and pharmaceutical companies in India, selected by MoEF, Government of India. She has authored 25 research articles. She has one international patent based on her Post-doctoral research. She is also the Life Member of several national and international scientific societies, Elected Member of PSI and Advisory Board Member of some national conferences.

Abstract:

Statement of the Problem: Tobacco smoking (nicotine) is associated with addiction behavior, drug-seeking and abuse. Several organ systems can also be affected by nicotine/smoking. However, the mechanisms that mediate this association especially, the role of brain-derived neurotrophic factor (BDNF), dopamine (DA) and nuclear factor erythroid-2 related factor-2 (Nrf2) signaling in the cerebral cortex as well as local neurochemical system in the testis, are not fully known.

Aim: The aim of the present study is to explore the toxic consequence of short- and long-term exposure and withdrawal in adult rodent models.

Methodology: We treated male Wistar rats with different doses of oral nicotine and passive smoking for 4-week (short-term) and 12-week (long-term) duration, where doses closely mimic the human smoking scenario. Also, in the precipitated withdrawal model, nicotine acetylcholine receptor blocker Mecamylamine, was given intraperitonially after nicotine treatment followed by biochemical, immune-histological, molecular and statistical analyses.

Findings: The dose- and time-dependent anxiogenic and depressive behavior and cognitive interference are associated with neurodegeneration and DNA damage in the cerebral cortex from layer II onwards upon exposure to nicotine/smoking. Further, the dose- and time-dependent loss of developing spermatogonia and spermatocytes of the seminiferous tubules, disruption of basement membrane and DNA damage, results in low sperm count by smoking/nicotine treatment. Upregulation of pro-oxidants, i.e., reactive oxygen species and inducible nitric oxide synthase (iNOS), over-expression of BDNF, DA and DA marker, tyrosine hydroxylase are linked with concomitant downregulation of antioxidants i.e., ascorbate and Nrf2 in both the exposed cerebral cortex and testis. High serum cotinine of the exposure models of short and long durations are found to be reversed in the withdrawal model. Also, the reversible expressions of Nrf2, iNOS, DA and DA receptor along with tissue architecture are observed in the same area of the cerebral cortex and testis during Mecamylamine treatment, probably due to inhibition of nicotinic effects on both the tissues by releasing pituitary gonadotrophins. However, BDNF expression is not affected by Mecamylamine in the present study, as BDNF might follow differential response pattern upon nicotine withdrawal.

Conclusion & Significance: The intervention of BDNF-DAergic signaling and depletion of antioxidants are important factors in pathogenesis of the cerebral cortex and testis during nicotine/tobacco smoking, leading to neurobehavioral and reproductive impairments respectively, which are counteracted by Mecamylamine, resulting in reversal of nicotine-induced tissue lesion upon withdrawal through upregulation of Nrf2-ARE-mediated transcription mechanism. Thus, our results confirm the beneficial role of the receptor blocker in local BDNF-DAergic circuit of the testis and cerebral cortex that could underpin the novel therapeutic approaches targeting tobacco smoking/nicotine’s neuropsychological disorders including drug addiction.

Biography:

Wei Li has his expertise and passion in fundamental biological and medical research, particular in areas related to three-dimensional structures of biologically relevant macromolecules and experimental data-driven molecular dynamics (MD) simulation and molecular docking and modeling. After years of wet- and dry-lab experience in research (including solution-state NMR, python programming and high-performance computer usage), he has developed a set of skills to uncover novel structural/functional insights through computational analysis of experimentally determined structures of biological molecules. Here, as an example in spinal muscular atrophy-related studies, his work presented the first attempt to link clinically identified SMA-linked mutations of SMN1 to the structural/functional deficiency of SMN, the protein that is critical to this neuromuscular disease.

Abstract:

Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disease with dysfunctional α-motor neurons in the anterior horn of the spinal cord. SMA is caused by loss (~95% of SMA cases) or mutation (~5% of SMA cases) of the survival motor neuron 1 gene SMN1. As the product of SMN1, the SMN protein is a key component of the SMN complex, and also involved in the biosynthesis of the small nuclear ribonucleoproteins (snRNPs), which play critical roles in pre-mRNA splicing during the pathogenesis of SMA. To investigate how SMA-linked mutations of SMN1 lead to structural/functional deficiency of SMN, a set of computational analysis of SMN-related structures were conducted and are presented. Of extraordinary interest, the computational structural analysis highlights three SMN residues (Asp44, Glu134 and Gln136) with SMA-linked missense mutations, which cause local disruptions of electrostatic interactions for Asp44, Glu134 and Gln136, and result in three functionally deficient SMA-linked SMN mutants, Asp44Val, Glu134Lys and Gln136Glu. From the computational structural analysis, it appears also possible that SMN’s Lys45 and Asp36 act as two electrostatic clips at the SMN-Gemin2 complex structure interface, structurally stabilizing the SMN-Gemin2 complex. Moreover, the structural analysis of a group of four further SMA-linked mutations (Trp92Ser, Trp102X, Ala111Gly and Ile116Phe) highlight the potential significance of the deeply buried hydrophobic side chains of Trp92, Trp102, Ala111 and Ile116 in the SMN Tudor domain, the essential part of SMN for its ability to bind the Sm proteins of snRNPs

Biography:

S Mondal has completed his PhD from Indian Veterinary Research Institute, Bareilly and Postdoctoral studies from Laval University, Canada. He is presently working as Principal Scientist at NIANP, Bangalore. He has been working in the field of molecular endocrinology, reproductive genomics and stress physiology for last 20 years. He has published over 55 papers in various national and international journals of repute. He has also received several prestigious awards like Siri Research Award, Prof. G P Talwar Midcareer Scientist Award, Prof. G K Pal Award, Fellow of Indian Chemical Society, Fellow of Society for Applied Biotechnology, Fellow of Indian Association of Biomedical Scientists, Dr. K Anji Reddy Award, Prof. P B Sen Memorial Oration Award, Biotechnology Overseas Associateship Award (Long term), ISSRF Young Scientist Award and Indian Science Congress Association Award.

Abstract:

Statement of the Problem: Prostaglandins (PGs) play an important role in regulation of estrous cycle, recognition of pregnancy and implantation in ruminants. The first limiting step in the generation of PGs is the transformation of arachidonic acid by cyclooxygenases-1 and -2 (COX-1, -2). The downstream enzymes, prostaglandin E synthase (PGES) and prostaglandin F synthase (PGFS) catalyze the conversion of PGH₂ into PGE₂ and PGF_2a, respectively. PGF_2a acts as the luteolytic agent to control estrous cycle whereas PGE₂ helps in implantation and maintenance of pregnancy. PGF_2a exerts its autocrine/paracrine action by binding to its receptors to mobilize intracellular Ca²⁺ and IP₃. Activation of FP receptors by PGF2α results in phospholipase C activation, inositol triphosphate hydrolysis and intracellular calcium flux. Pharmacological inhibition of FP receptor antagonist (AL 8810) has been found to decrease PGE₂ production in human endometrial cells treated with IL-1β.

Purpose: The purpose of this study is to explore the effect of PGF_2a receptor antagonist on prostaglandin production and protein expression in bovine endometrial epithelial cells.

Methodology & Theoretical Orientation: Endometrial epithelial cells at the stage of confluence were incubated with vehicle and/ FP receptor antagonist (AL 8810) for 30 min. Thereafter, the cells were stimulated with vehicle, OT, IFN and OT+IFN in absence and/ presence of AL 8810 for 6 hrs.

Findings: Oxytocin had been found to increase the production of PGF_2a in cultured cells in presence of both 10 µM and 25 µM AL 8810 but production was more with 10 µM AL 8810 treatment group. Similarly, OT increased PGE₂ production in presence of 10 µM AL 8810 in epithelial cells. The expression of COX-2 protein increased by treatment of AL8810 in presence of OT and OT+IFN but decreases in the presence of IFN alone.

Conclusion & Significance: Production of prostaglandin and COX-2 expression are modulated by PGF_2a receptor antagonist

Biography:

Riad H. Khalil is a senior professor of Fish diseases, Department of Poultry and Fish diseases, faculty of Veterinary medicine in Alexandria University. He has over 15 years working experience fish microbiologist and research focusing on fish diseases and water resource management. He has contributed more than 75 articles in local and international scientific journals and has supervised 45 PhD and 85 master students

Abstract:

A total 3000 pieces of sea bass (Dicentrachus labrax) fingerlings were stocked in a nursery earthen pond by the rate of 3000 pieces with body weight ranges between 40 to 50 grams per pieces in 1000 cubic meters and 90 fish (30×3 replicates) were stocked in aerated aquaria to assess the effects of essential oil of Origanum vulgaris and challenged with 0.5 ml of a virulent strain of Vibrio algenolyticus at 4×10⁶ cells/ml administered intraperitoneally. The experiments were conducted in two phases (In situ phase and Aquarium phase) to evaluate the essential oils of Origanum vulgare at different concentrations 0.5 and 1 ml/kg feed on various antioxidants enzymes activities in liver tissue and to determine antimicrobial activity against different bacteria, fungus and yeasts and detection of gene expression of cytokine from liver as well as effect on Vibrio algenolyticus challenged fingerlings of sea bass. The results revealed that the essential oils of Origanum vulgare increases the catalase activity and severe drop of lipid peroxidation level in liver tissues compared with control group. In the liver of sea bass supplemented with essential oil of Origanum vulgare caused down regulation of HSP. In addition to the essential oils of Origanum vulgare, it has antimicrobial affects against wide range of bacterial and fungal agents of cultured fish. In conclusion the current results demonstrate the oils of O. vulgare (0.5 ml and 1 ml kg^-1) improving the fish health status and immune resistance against Vibrio alginolyticus infection and act as antimicrobial and antioxidant

Biography:

Santanu is currently the CSO of Bugworks antibiotics discovery SME. Prior to this, he was the Principal Research Scientist in AstraZeneca India, where he spent more than 2 decades working in Infectious diseases, with a focus on Malaria and MTB. At AstraZeneca, Santanu scientifically mentored programs across the discovery pipeline and pioneered many ground-breaking concepts such as those of gene and chemical vulnerability. He has served as Principal Investigator in several prestigious research grants from Wellcome Trust, EU and DBT India. His current interest is in systems biology and its application in anti-infective drug discovery and in Industrial Biotechnology specifically the interface between insilico and experimental biology. Santanu, received his Ph.D. from Calcutta University in Biophysics in 1981 and was trained as a molecular biologist during his post-doctoral stint in Indian Institute of Science, Baylor College of Medicine USA and Karolinska Institute Sweden

Abstract:

The mechanism of efflux is a tour de force in bacterial armoury that has thwarted discovery of novel antibiotics. We reported the discovery of a novel series of compounds with potent antibacterial properties that is devoid of efflux liability. Starting from a phenotypic screen with a library diverse molecule on a panel of efflux deficient E. coli strains, we progressed a nitro-thiophene carboxamide derivative that effluxed selectively via the efflux pump AcrAB-TolC. Binding of these molecules to AcrB was evaluated by fluorescent thermal shift and Nile red dye-based assays. Prospective in silico modeling using computational methodologies viz. molecular docking and MD simulations were done. Iterative design and synthesis based on binding potency by in vitro assays and in silico prediction led to the generation of a series of molecules that were potent on wild type and multi-drug resistant clinical isolates of E. coli, Shigella spp. and Salmonella spp. Using a novel system biology reverse MOA (mechanism of action) protocol that measures the synergistic sensitivity on library of specially curated single gene knockout sub-library from the KIEO strains we identified these molecules to be pro-drugs that are activated inside E. coli by specific bacterial nitro reductases NfsA and NfsB. The conversion of these pro-drugs was characterized by in vitro enzymatic assay of purified NfsA and NfsB. Furthermore, these molecules were shown to be bactericidal and efficacious in a mouse thigh infection model.

Biography:

Krishna Dronamraju is President of the Foundation for Genetic Research, Houston, and a Visiting Professor of the University of Paris. He was a student and close associate of J.B.S. Haldane, receiving his Ph.D. in human genetics from the Indian Statistical Institute, and later worked with Dr. Victor McKusick at the Johns Hopkins University School of Medicine. Dr. Dronamraju is the author of 19 books and over 200 papers in genetics and biotechnology. He was an Advisor to President Bill Clinton’s administration and was a member of the United States Presidential delegation to India in 2000. He served on the Recombinant DNA Advisory Committee of the U.S. National Institutes of Health, Washington, D.C.

Abstract:

Synthetic biology is concerned with the design and construction of new biological parts, devices and systems and the re-design of existing, natural biological systems for useful purposes. The convergence of scientific fields such as molecular biology, computer science and others has rendered it a natural progression, based on existing knowledge. The fact that humanity has reached a stage of development where it seems feasible to create life, or design it to a high degree of specificity, is a significant milestone in its history. It generates important ethical questions: Is synthetic biology something good, a natural use of humanity’s talents, or is it a step towards megalomania, playing God, a usurpation of his role? Is it really a natural progression, nature advancing to a state where its products can, in turn, improve nature itself; or does it challenge the dignity of nature by virtue of its unnaturalness? Is it an expression of the creative talent of humanity, thus enhancing human dignity and perhaps that of all life, or does it challenge the dignity of life itself? Regarding its potential consequences, it may, if it succeeds, lead humanity to a new level of development, a paradigm shifts comparable with the scientific or industrial revolutions, through a vast increase in scientific knowledge and subsequent technological developments in all relevant areas, including medicine, food production and fuel development. However, there is potential for serious accidents if synthetic organisms interact with naturally occurring ones, possibly affecting the future course of evolution. Synthetic biology also offers the possibility of creating ever more powerful weapons. It offers potential for both good and evil which appears to be greater than any other technology that has existed.

Biography:

Jae-Sun Choi has received her BS at Pusan National University and her PhD in Biomedical Science in 2011 at Kyung Hee University, South Korea. She was a Post-doctorate at Kyung Hee University, where she worked in projects about tumor angiogenesis between 2011 and 2016. Since 2016, she is a Research Fellow at Kyung Hee University. She has eight years of experience in basic research with expertise in both Parkinson’s disease and tumor angiogenesis. Her research interests focus on the effect of natural compound on Parkinson’s disease and the novel mechanism mediated by HIF-1alpha of tumor angiogenesis.

Abstract:

Background & Aims: Progressive dopaminergic neurodegeneration is responsible for the cardinal motor defects in Parkinson’s disease (PD). PD researchers still have limited understanding of the key molecular events that provoke the selective dopaminergic neurodefects in this disease. The present study examined whether brain-specific angiogenesis inhibitor (BAI1) participates in the pathway of dopaminergic neuronal loss in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD.

Method: We constructed a PD model to evaluate the role of BAI1 on neuronal cell survival. Eight-week-old male C57BL/6 mice were randomly assigned to a saline group and MPTP (20mg/kg×4/day, 2 hours intervals). Moreover, mouse mesencephalic neurons and SH-SY5Y cells were treated with 10 μM and 300 μM (or 500 μM) of MPP⁺ for 24 hours, respectively.

Result: BAI1 immunostaining of brain sections from MPTP-treated mice showed that BAI1 was significantly decreased. Moreover, BAI1 level was specifically decreased in dopaminergic neurons in the substantia nigra of MPTP-toxicated mice. In primary mouse mesencephalic neurons and human neuroblastoma cell lines, 1-methyl-4-phenylpyridinium (MPP⁺) which is a toxic metabolite of MPTP also suppressed the expression of BAI1. We applied a bioinformatics tool to extend upstream regulatory pathway of BAI1 expression. AMP-activated protein kinase (AMPK) was predicted as a regulator and consequently AICAR, a specific activator of AMPK, reduced the BAI1 protein level. BAI1 overexpression decreased nuclear condensation induced by MPP⁺ treatment.

Conclusion: Down-regulated BAI1 by AMPKα induces neuronal cell death in PD model and BAI1 could play a crucial role as cell survival factor in neurodegenerative pathway of PD.