Day 2 :
Technion-Israel Institute of Technology, Israel
Keynote: Targeting the Intracellular Proteome with T cell Mimicking antibodies; Structural and Functional Properties.
Time : 10:00-10:45
Yoram Reiter is a Professor and the Sebba Chair in Sciences at the Faculty of Biology Technion-Israel Institute of Technology, Israel. He Heads the Laboratory of Molecular Immunology and is also the Director of the Lokey Interdisciplinary Center for Life Sciences and Engineering at the Technion. His lab develops new approaches for cancer immunotherapy and other molecular engineering approaches for autoimmunity using recombinant antibodies and MHC molecules. He has published >100 scientific papers and reviews as well as >30 patents in the fields of antibody engineering, immunotherapy and molecular immunology. He is the Co-Founder of Applied Immune Technologies (AIT) which develops T cell receptor like antibodies for clinical applications.
We have created a unique class of human monoclonal antibodies that mimic the ability of the T cell receptor to recognize intracellular antigens in the context of the major histocompatibility complex (MHC). This approach harnesses the power of the cellular arm of the immune system to attack diseased cells with soluble, readily made human monoclonal antibodies. Distinct from conventional monoclonal approaches that only attack cell surface-associated proteins; this approach of generating T cell receptor-like antibodies now addresses the far more abundant intracellular proteome. The combination of these features opens entirely new vistas for the treatment of many kinds of diseases in oncology, autoimmunity and inflammation. The molecular properties of this unique family of molecules as well as the structure-function relationships studies will be presented considering their binding specificity properties.
- Structural Bioinformatics and Proteomics |Structural Biology and Single Molecules |Molecular Modeling and Dynamics|3D Structure Determination|Computational Approaches in Structural Biology|Structural Molecular Biology| Structural Virology |Hybrid Approaches for Structure Prediction|Sequencing|Drug Designing|Signaling Biology|Frontiers in Structural Biology |Recent Advances in Structural Biology |Structural Biology in Cancer Research|Structural Biology Complexity Arenas
National Institute of Occupational Health, India
Title: Tobacco smoking and nicotine modulate Nrf2-BDNF-Dopaminergic signaling in cerebral cortex and testis of adult rats during addiction and withdrawal
Time : 11:00- 11:30
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.
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.
Shantou University Medical College, China
Title: Title: How do SMA-linked mutations of SMN1 lead to structural/functional deficiency of the SMA protein?
Time : 12:00-12:30
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.
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
National Institute of Animal Nutrition and Physiology, India
Title: Effect of PGF2 receptor antagonist on prostaglandin production and COX-2 protein expression in bovine endometrial epithelial cells
Time : 12:30-13:00
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.
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 PGF2a, respectively. PGF2a acts as the luteolytic agent to control estrous cycle whereas PGE2 helps in implantation and maintenance of pregnancy. PGF2a 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 PGF2a 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 PGF2a 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 PGF2a receptor antagonist
Alexandria University, Egypt
Title: Modulatory effect of different doses of essential oils of Origanium vulgare on the antioxidant, antimicrobial and immune-related genes of seabass Dicentrachus labrax challenged with Vibrio alginolyticus
Time : 14:00-14:30
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
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
Bugworks Research, India
Time : 14:30-15:00
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
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.
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.
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.
Kyung Hee University, South Korea
Title: Expression of brain-specific angiogenesis inhibitor-1 is decreased and regulated by the AMPK pathway in Parkinson’s disease
Time : 11:30-12:00
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.
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.