International Conference on Synthetic Biology September 28-29, 2015 Houston, USA

Session Introduction

Vsevolod V (Seva) Gurevich

Vanderbilt University, USA

Title: Mass production of high fidelity oligonucleotides as feed stock of Post-genome-sequencing synthetic biology (PGS-SB)

Time : 11:00-12:30

Biography:

Vsevolod V (Seva) Gurevich has completed his PhD in 1989 from Shemyakin Institute of Bioorganic Chemistry, Moscow, Russia, and postdoctoral training (1991-1995) in the laboratory of Dr. J L Benovic, Thomas Jefferson University, Philadelphia, PA. He is Professor of Pharmacology at Vanderbilt University. He has published more than 160 papers in reputed journals and has been serving as an editorial board member of several journals.

Abstract:

Virtually every protein is multi-functional. Over-expression or knockdown/knockout by definition enhance or suppress all functions of targeted proteins. Thus, these methods are inherently unsuitable to elucidate biological role of individual functions. Re-engineered of signaling proteins to enhance or suppress a single function out of many is a viable alternative. However, in contrast to over-expression or knockout, this approach requires in-depth knowledge of the molecular mechanisms of each function of the protein of interest. Relatively few proteins are studied in sufficient detail to make this possible. We will discuss this approach using arrestin proteins as an example. Arrestins are ultimate multifunctional scaffolds, organizing multi-protein signaling complexes and localizing them to particular subcellular compartments. Extensive mutagenesis and structural work revealed the molecular basis of at least some arrestin functions, enabling the construction of signaling-biased arrestins, as well as the use of their mono-functional elements to elucidate the biological role of their functions. Arrestins regulate G protein-coupled receptors, cell adhesion and motility, as well as MAP kinase signaling involved in life-or-death decisions of the cell. Therefore, reengineered “designer” arrestins and their parts are useful tools for experimental manipulation of cell behavior. Practically every disorder is associated with faulty signaling. Signaling-biased arrestins and other regulatory proteins allow us to channel cell signaling in desired direction, which has enormous therapeutic potential.

Weiwen Zhang

Tianjin University

Title: Synthetic photosynthetic Cyanobacteria to produce fine chemicals directly from CO2

Biography:

Dr. Zhang is a Professor of Microbiology and Biochemical Engineering, Head of Laboratory of Synthetic Microbiology in the School of Chemical Engineering and Technology of Tianjin University in China. Prior to joining Tianjin University, Prof. Zhang was a faculty with Biodesign Institute and the School of Life Science of Arizona State University for 2007-2011, and a senior scientist at Microbiology Department with the Pacific Northwest National Laboratory of the U.S. Department of Energy (DOE) for 2002-2007. Dr. Zhang has broad research experience in microbial genetics, physiology and synthetic biology, has authored more than 130 peer-reviewed scientific papers. His recent research focuses on synthetic biology of photosynthetic microorganisms and analysis of microbial consortia.

Abstract:

Photosynthetic Cyanobacteria have attracted significant attention as a “Microbial factory” to produce biofuels and various fine chemicals, mostly due to their abilities to utilize CO2 and sunlight directly as carbon and energy sources, respectively. We will report our recent progress on engineering cyanobacterium Synechocystis sp. PCC 6803 to produce 3-hydroxybutyrate (3HB), 3-hydroxypropionic acid (3HP) and butanol directly from CO2, and on strengthening Synechocystis for better tolerances against toxic products.

Mateus Schreiner Garcez Lopes

Innovation in Renewable Technologies - Braskem – Brazil

Title: Driving innovation with renewable chemicals platform - the role of synthetic biology in the petrochemical industry

Biography:

Mateus Schreiner Garcez Lopes has completed his PhD at the age of 27 years from University of São Paulo/Brazil and University of Erlangen/Germany. His postdoctoral studies were at University of São Paulo and he holds a MBA in Agribusiness also from the University of São Paulo. He had worked as researcher at the Natural Energy Institute (Hawaii- USA) and the Institute of Biotechnology from UNAM (Mexico). He is responsible for the Innovation in Renewable Technologies at Braskem, the largest petrochemical producer in the Americas and the world's leading biopolymer producer. He has published in international journals, has issued patents on new metabolic pathways and is serving as an industrial board member for Synberc (Synthetic Biology Research Center - USA).

Abstract:

Braskem reinforce the leadership in bio-thermoplastic, by signing a development agreenment with Novozymes in 2012 for the development of bio-polupropylene. Both world-class companies are working together for the reinforce Braskem vision in the thermoplastics segment. Going forward into other markets, Braskem design a bio rubber platform in partnership with two synthetic biology start-ups. The company have signed an agreement for the joint development of two new technology for the production of butadiene and isoprene from renewable feedstocks with Genomatica (signed in 2013) and Amyris (signed in 2014), respectively. Through this partnership, Braskem reaffirms its commitment to invest in the research of producing chemicals from renewable feedstocks, effectively strengthening its leadership in synthetic biology. Braskem has invested in one of the most advanced laboratory in South America. A 7000 ft2 facility with a m Braskem vision is to be world leader in sustainable chemistry, innovating to better serve people. To transform this vision into reality, we are believe that synthetic biology will empower new technologies and transform our society. I am current responsible for biotech innovation at Braskem and my lecture will present why we choose synthetic biology as a platform for industrial biotechnology and what is our strategy to move forward in this field. ultidisciplinary and international team in a variety of areas, including synthetic biology, protein engineering, automation, bioinformatics, fermentation and downstream processes. The research program conducted within Braskem seeks not only to find alternatives that are based on renewable feedstocks, but on developing routes that are also competitive in terms of production cost.

Teresa Cristina Zangirolami

Federal University of Goiás, Brazil

Title: Improved ethanol production from D-xylulose through evolutionary engineering of wild baker´s yeast

Biography:

Teresa Cristina Zangirolami has completed her PhD from Technical University of Denmark. She is a Lecturer and Researcher at the Chemical Engineering Department of Federal University of São Carlos and works in close cooperation with researchers from Butantan Institute and from the Department of Biological Engineering (University of Minho, Portugal). She has published more than 30 papers in reputed journals and has been serving as an Editorial Board Member of repute.

Abstract:

For enhanced economic feasibility of second generation bioethanol production, it is important to use all the fermentable fractions present in sugarcane bagasse (cellulose-C6 and hemicelluloses-C5) or other feedstocks. Xylose is the main sugar found in the C5 fraction and is not assimilated by Saccharomyces cerevisiae. However, this yeast is able to ferment D-xylulose, an isomer of xylose which can be obtained using glucose isomerase generating ethanol and xylitol as main products. This study aims to select a more suitable ethanol producer strain exhibiting lower xylitol production. Colonies isolated from industrial yeast were exposed to a sequence of evolutionary engineering procedures: Incubation on complex solid media containing xylulose (aerobic conditions); incubation of selected colonies in minimal solid medium (anaerobic conditions) and cultivation of 20 adapted colonies in cuvettes containing YNB medium and xylulose. Three colonies exhibiting lowest xylitol production were identified and characterized in terms of product formation and substrate uptake under micro aerobic conditions at 30° C. selected mutant and wild-type strains were further compared in terms of morphology and genotype. With a final ethanol concentration of 4.3 g/L for a xylitol production of 0.55 g/L, the adapted yeast showed selectivity values up to 26 mol ethanol/mol xylitol. The morphology analysis revealed that mutant strain was not able to metabolize bromocresol green dye and its colonies exhibited a darker green color on WLN agar. The results of genotypic analysis also confirmed that evolutionary engineering was able to introduce several mutations in the selected yeast.

Masoud Sheidai

Shahid Behesti University, Iran

Title: Olive biotechnology: The assessment of tissue culture induced genetic variability in olive (Olea europaea) by molecular markers

Biography:

MASOUD SHEIDAI has completed his PhD at the age of 28 years from Poona University India and Sabbatical studies from UBC University in Canada. He is now proffessor of Biology in Shahid Beheshti University, Tehran, Iran. He has published more than 125 papers in reputed journals and has been serving as an editorial board member of repute. Gene Conserve, and Bidiversity journals.

Abstract:

Olive is one of the most important tree crops of the country and it is cultivated in many places. Propagation of true to type olive plants is important for many olive companies and farmers in the country and for this reason genetic analysis of randomly selected tissue culture regenerated olive plants of cultivars Kroneiki, Zard, Roughani and X was performed and compared with the mother plant. We used Cp-DNA and RAPD molecular markers to check genetic fidelity versus somaclonal variation. Both RAPD and Cp-DNA analyses revealed that some of the regenerated plants differed extensively in their genetic content. These plants were placed in different clusters far from the mother plants in NJ tree and TNT tree obtained from these two molecular markers. We identified also some regenerated plants that were true to types of the mother plants. These plants also differed in their morphological features. Genetic and morphological changes were more extensive with increase in sub-culture numbers. Different uses of these two types of plants will be discussed.

Chair

Vsevolod V (Seva) Gurevich

Vanderbilt University Medical Center, USA

Co-Chair

Mehmet Sen

Harvard Medical School, USA

Session Introduction

Stevens M Brumbley

University of North Texas, USA

Title: Metabolic engineering of a high biomass C4 grass for commercial scale production of bioplastics

Time : 12:30-13:00

Biography:

Stevens M Brumbley completed his PhD at the University of Georgia in 1992 and postdoctoral studies at the University of California Riverside in 1993. He worked in the Australian Sugarcane Industry from 1993 to 2006 and at the University of Queensland’s Australian Institute for Bioengineering and Nanotechnology for 2006 to 2011. He is currently a tenured Associate Professor of Plant Metabolic Engineering at the University of North Texas. He has published more than 50 papers in high impact journals.

Abstract:

Sugarcane is an important high biomass crop grown throughout the tropical and subtropical regions of the world. In Brazil, sugarcane has a central role in not only the production of sucrose but also in the production of biofuels and bio-based chemicals. In the future, these bio-based chemicals may be derived not only from bio-refineries but also from genetically engineered sugarcane itself. We have been metabolically engineering sugarcane to function as a bio-factory producing bio-plastics and bio-plastic precursors. Sugarcane was metabolically engineered to produce polyhydroxybutyrate (PHB), a member of the class of biopolymers known as polyhydroxyalkanoates (PHA). Most of our work has focused on PHB using a three enzyme pathway from a soil bacterium (Ralstoniaeutropha) [β-ketothiolase (PhaA), acetoacetyl-reductase (PhaB) and PHB synthase (PhaC)]. Transgenes were expressed in the nucleus of sugarcane and the enzymes were targeted to plastids. In plastids, using a maize polyubiquitin promoter, PHB granules were detected in all cell types in sugarcane stalks and leaves, however, the highest accumulation was in bundle sheath cells. A number of strategies were used to increase the levels of PHA accumulation in sugarcane leaf tissue. An early detection system was developed using Nile Blue. A staining and fluorescent microscopy showing that PHA could be detected in leaf tissue from tissue culture plantlets regenerated from the transgenic callus. When a stronger promoter was used (maize chlorophyll A/B binding protein promoter) PHA accumulation was significantly higher in leaf tissue of sugarcane. Knocking out competition for acetyl-CoA in sugarcane resulted in a 50% increase in PHB levels in leaves. Replacing PhaA with a novel enzyme resulted in another 4 fold increase in PHA levels resulting in leaves producing commercial levels of PHA. In addition to plastid production, PHB and PHB/PHA copolymers were engineered into sugarcane peroxisomes by targeting the PhaA, PhaB, and either PhaC or the Pseudomonas aeruginosa PhaC1 to peroxisomes. We found both PHB and PHB/PHA copolymer granules localized in peroxisomes and vacuoles in sugarcane leaves. The biopolymers we are producing have very high molecular weight with the highest at close to two million daltons. The highest production level of PHA polymer recorded to date in sugarcane is 12% of the total leaf dry weight.

Soumendra Rana

Indian Institute of Technology Bhubaneswar, India

Title: Structural modeling of C5a receptor: Molecular insights into agonism and antagonism

Time : 14:00-14:30

Biography:

Soumendra Rana has completed his PhD at the age of 29 years from IIT Bombay and postdoctoral studies from Washington University School of Medicine in St. Louis, including University of Arizona, Tucson. He is currently an assistant professor (Chemistry and Biosciences) at the IIT Bhubaneswar, one among the 14 premier technical institutes of the country. He has published more than 12 papers in reputed journals and has been serving as an editorial advisory board member in International Journal of Chemical and Pharmaceutical Review and Research.

Abstract:

The complement component fragment 5a receptor (C5aR), also known as the anaphylatoxin receptor is one of the two major G-protein coupled receptor (GPCR) that demonstrates a high affinity interaction with C5a, the most potent pro-inflammatory polypeptide of the complement system, known for its pleiotropic effects in both immune and non-immune cells. No wonder, the C5a-C5aR interaction has been tagged druggable for discovery of targeted therapeutics.1 However, the molecular basis of agonism or antagonism in C5aR is yet to be established clearly, largely due to the unavailability of a structure of C5aR. In addition, while the role of allosterism in C5aR is discussed in the literature, it is completely unheard for C5a, a potential drug target that modulates the downstream signaling of C5aR. It not only hinders the discovery and development of new lead molecules, but also affects the rational optimization of the known lead molecules as potential therapeutics, targeting the C5a-C5aR signaling axes. In our quest toward better understanding of C5a-C5aR interaction, 2 we have recently generated the first set of atomistic model structures of inactive and meta-active C5aR in excellent agreement with the previously reported binding and signaling studies. 3 Further, we have also identified a pair of “allosteric switches”4 on C5a that potentially modulate the C5aR signaling. It is noteworthy that the peptide agonist, C5a and the small molecule antagonist5 NDT demonstrate binding at the exact same site on the meta-active structure of C5aR with distinctly different binding modes.6 In summary, the inactive, agonist and antagonist bound meta-active C5aR structures provide important structural insights, previously not known at an atomistic resolution, in regard to the ligand binding sites, selectivity and activation of C5aR, which will be discussed in detail.

Xiaolian Gao

University of Houston, Houston TX

Title: Mass production of high fidelity oligonucleotides as feed stock of post-genome-sequencing synthetic biology (PGS-SB)

Time : 14:30-15:00

Biography:

Xiaolian Gao co-founded VisiGen Biotechnologies, Inc., in 2000. She is Professor of Chemistry, Biology and Biochemistry and Director of the Keck/IMD NMR Center at the University of Houston. After spending more than two years working at then Glaxo Pharmaceuticals as a Principle Research Investigator in structural biology, she joined the Department of Chemistry at the University of Houston. At the Keck NMR Center that she established at the University, she has collaborated with many groups in Houston and nationwide. Her group has discovered and published unique structures of biologically important DNA and ligand-DNA complexes. Pursuing research in the interdisciplinary areas of chemistry and biology, she developed novel methods for massively parallel synthesis of biomolecule and chemical microarrays, which became the founding technology of Xeotron Co. Ms. Gao holds a BS degree from the Beijing Institute of Chemical Engineering and PhD in Chemistry at Rutgers University. During her postdoctoral work in NMR-based structure biology at the medical school of Columbia University in late 80’s she was among the first few who solved the structures of several important Ligand-DNA complexes using high resolution nuclear magnetic resonance (NMR) spectroscopy.

Abstract:

Rapid progress in genome sequencing and functional genomics has set up the stage for a new era of engineering-based postgenome- sequencing synthetic biology (PGS-SB). As the blueprints, i.e., the DNA coding sequences, of biological devices of specific functions are largely known, engineering these devices, further bio-systems which are made of designed devices are tacks of construction of structures of hundreds and thousands of nucleotides in defined orders and contents. Oligonucleotides thus become the fundamental building blocks of aforementioned bio-devices and systems. We report a micro-fluid microarray chip technology platform, for programmable engineering oligonucleotides in quality and quantity which coupled with a seamless workflow for generation of high fidelity oligonucleotides, we will demonstrate the application of these polynucleotides in a varieties of PGS-SB applications. Our goal was to offer affordable solutions to general laboratories interested in PGS-SB.

Pushpa Agrawal

R. V. College of Engineering, India

Title: Development of green formulation for dual purpose of disease management and plant development

Time : 15:00-15:30

Biography:

Pushpa Agrawal has completed her PhD degree in the year 1984 from DAVV, Indore and Post-doctoral studies from Miami University, USA and India Institute of Science Bangalore, India. She is a Professor of Biotechnology and Dean, Post-graduate studies in Biotech and Chemical Engineering at R. V. College of Engineering, Bangalore India. Many scholars are pursuing and completed PhD under her guidance. She has presented over 100 research papers in conferences and published more than 40 papers in reputed journals. She has co-authored a book on biotechnology and chapters in 2 books and has been serving as Managing Editor and Editorial Board Member of reputed journals. She has also received various awards, honors and fellowships.

Abstract:

The use of chemical fertilizers and pesticides in commercial farming gives the threat of gradual aggravation of soil fertility. Use of agriculturally important microorganisms in different combinations is the only solution for restoration of soils. The bio-formulations using humic acid with suitable bio-control microorganisms namely, Pseudomonas fluorescens and Trichoderma harzianum have been developed to replace chemical fertilizers. Trichoderma harzianum is a major bio-control agent against a wide range of phyto-pathogenic organism of economically important crops and extensively used in various parts of the world for plant disease management. These bio-control agents are also known to degrade complex organic molecules into simpler molecules which help to improve soil fertility. Humic acid is an organic fertilizer which enhances the plant growth. The bio-organic formulations have been developed for controlling or suppressing of fungal diseases (Fusarium species) as well as to increase the plant growth and yield by increasing the soil fertility in an eco-friendly manner. The present report reveals an additive effect of microorganism with humic acid in both disease management and better plant growth. The results revealed that the Trichoderma harzianum with 2% humic acid based formulation was effective in inhibiting Fusarium growth in vitro. The liquid bio-formulation of humic acid along with the Pseudomonas fluorescens was tested and compared for viability as well as its inhibitory characteristics against Fusarium oxysporum, a fungus which cause wilt of tomato. Cell viability tests were carried out for the bio-formulations by plate count method. Field studies were conducted for two crop varieties-radish and tomato. The results of in vivo and in vitro studies revealed better support for the viable cells as well as leafing and fruit

Session Introduction

Gustavo Stadthagen

BIOASTER, France

Title: Controlled ultrasound cavitation for DNA delivery into bacteria and yeast

Biography:

Gustavo Stadthagen holds PhD in Microbiology from the University of Paris Denis Diderot. He has published more than 10 articles on Molecular Genetics and Biochemistry of Infectious Agents, Cancer Cells and Biotechnology Relevant Microorganisms. He currently works as a Research Scientist at the Unit of Protein and Expression System Engineering of BIOASTER, a new technology research institute on infectiology and microbiology. His research using an integrated approach that includes enhanced recombinant DNA construct design, assembly, delivery and stabilization aims to develop improved protein expression systems for biopharma and biotech applications.

Abstract:

Sonoporation is an ultrasonic cavitation-dependent method for gene delivery, mostly applied to higher eukaryotic cells and tissues. Cavitation in the vicinity of cells induces pore formation in the cell envelope and mechanical internalization of extracellular DNA. Its application to biotechnology useful organisms is less developed. Here we evaluated the CaviBoxR sonoporation device for plasmid delivery into the yeast Kluyveromyces lactis and the bacterium Escherichia coli BL21, commonly employed organisms for bio-production. CaviBoxR tightly controls cavitation through combination of multiple ultrasound beams under strong negative pressures. We evaluated the effect of different cavitation conditions (intensity, duration, duty cycle) and cell suspension media composition on cell viability and functional plasmid uptake. Optimal DNA delivery into K. lactis kept in YPD culture medium and incubated with linearized plasmid before sonoporation was achieved at CI 14 for 60 seconds with minimal effects on cell viability. Transformation efficiency was comparable to conventional chemical transformation of this host. Plasmid uptake by E. coli occurred in LB culture medium supplemented with 100 mM CaCl2 at CI 12-14 for 20 seconds. Under the same cavitation conditions, transformation was 100 times more efficient when bacteria were suspended in a solution of 25 mM MgCl2, 100 mM CaCl2 and 10% Glycerol. These first results demonstrate the feasibility of DNA delivery into bacteria and yeast species of biotechnological interest by sonoporation, directly in culture medium with minimal manipulation. Improvement of this method holds the potential of simple parallel transformation of large strain collections and or recombinant DNA libraries.

Richard McLean

University of Lethbridge, Alberta, Canada

Title: Mitigation of poultry-borne Campylobacteriosis by an engineered enteric commensal

Biography:

Richard McLean is a master student at University of Lethbridge Canada. McLean contributed to a ground-breaking study that was recently published in Nature, the world’s most-cited interdisciplinary science journal with work he accomplished as an undergraduate student in an Applied Study setting with Dr. Wade Abbott, an adjunct chemistry and biochemistry professor.

Abstract:

Campylobacter jejuni is the leading cause of human gastroenteritis in the developed world with cases in of Campylobacteriosis in Canada numbering nearly 50% of all bacterial foodborne illness. Primary infections are typically self-limiting however numerous secondary sequelae can develop including reactive arthritis, irritable bowel disorder, inflammatory bowel disease, and Guillain-Barre syndrome, the leading cause of acute fl accid paralysis in North America. Because as much as 70% of human Campylobacteriosis can be traced to the consumption of contaminated poultry, this project aims to prevent C. jejuni from proliferating in the chicken gut. Numerous approaches have been attempted previously including the addition of bacteriophages or bacteriocins to the feed, chicken vaccination, positive selection of C. jejuni free birds and a variety of methods to limit physical exposure of the birds to the bacterium. This project uses a synthetic biology approach to engineer the human gut commensal Bacteroides thetaiotaomicron to produce and secrete Nano-bodies within the chicken gut. Nano-bodies were raised against C. jejuni flagella and the focus of this project was to establish adequate expression levels, integrate required genes into the genome of B. theta and demonstrate the secretion of functional protein. The benefit of this approach will be the continued production of Campylobacter-active compounds within the chicken gut, which would be an economic and technological advancement over feed supplementation. In addition, this approach will enable the rational selection of therapeutic targets to help avoid the development of resistance.

Zehra Tatli

Hacettepe University, Turkey

Title: Comparison of intracellular and extracellular cellulase production by recombinant bacterium Escherichia coli

Biography:

Zehra Tatli is a Master of Science student in Bioengineering at Hacettepe University, Turkey and she has Bachelor’s of Science degree in Biology. Currently, she is working on her MSc thesis titled “Novel cellulase enzyme production towards biofuels sector by recombinant bacterium Escherichia coli” supported by TUBITAK (The Scientific and Technological Research Council of Turkey). She is interested in Synthetic Biology and wants to improve herself further during PhD studies on recombinant protein biogenesis in microorganisms and on the development of platform technologies for protein expression and engineering.

Abstract:

Low cost, pH and thermo-stable cellulase enzymes are an important factor for commercially viable production of bioethanol which is a renewable source of energy. Nowadays, the cost of cellulase accounts for 40-50% of the total ethanol production cost and it is targeted to be reduced 5-folds for commercial efficiency. Instead of food raw materials such as corn and sugar cane, ethanol obtained from cellulosic biomass by endoglucanase type of cellulase will reduce production costs. In this process, the choice of the host cell is extremely important in order to develop more economical production processes. Escherichia coli bacterium is one of the most preferred hosts for the production of recombinant proteins. On the other hand, enzymes produced in bacterial systems are known to be more economical compared to eukaryotic cells provided that they can be secreted in high amounts. In this context, recently codon optimized novel Cel5A enzyme was expressed intracellularly and extracellularly in E. coli and bioprocess optimization studies were followed by Western blot and spectrophotometric enzyme activity assays. We increased intracellular enzyme activity 50-fold up to 0.74 IU/mL and extracellular enzyme activity 5-fold up to 1.5 IU/mL. The recombinant cellulase enzyme and the bioprocess developed in this study have vital importance for overcoming the

Neema K N

Sri Jayachamarajendra College of Engineering, India

Title: In silico molecular docking of ligands for inhibition of L-amino acid oxidase from Calloselasma rhodostoma

Biography:

Neema K N is a Research scholar in Department of Biotechnology, Sri Jayachamarajendra College of Engineering. She is currently pursuing her PhD from JSS Research Foundation in affiliation with University of Mysore. She has been awarded with Junior Research Fellowship, UGC, Government of India. She has published a paper in reputed journal and has presented poster in 2nd National Conference of Toxicological Society of India.

Abstract:

L-amino acid oxidases (LAAO; EC 1.4.3.2) are flavo-enzymes catalyzing the oxidative deamination of L-amino acids and produces reactive oxygen species (ROS) including Hydrogen peroxide. H2O2 mediates in the process of cell death by necrosis, platelet aggregation, apoptosis etc. Several biological activities of LAAOs from snakes have been reported including apoptosis-inducing activity. Development of a lead with the combination of biological activity and drug like properties is needed. Both features can be estimated primarily by in silico virtual docking strategies in drug discovery and development. In this study, the crystal structure of L-amino acid oxidase 2IID was imported into Maestro 9.3 following subsequent removal of all crystallographic water molecules from the PDB. Bio-actives from several medicinal plants were screened for the inhibition of LAAO from Calloselasma rhodostoma. Th e possibility of binding, precise location of binding sites and mode of binding ligand was carried out using automated docking soft ware Glide XP. The efficacy was evaluated based on scoring function employed in Glide XP (Schrodinger platform). The promising compounds were employed for ADME/Tox studies. Our result showed that Limocitrin bioactive from Citruslimon completely buried deeply inside the catalytic tunnel, blocking the transfer of hydride ion at isoalloxazine ring resulting in obstruction for formation of H2O2, thereby inhibiting LAAO. Furthermore pharmacophore modeling suggests the better binding in presence of hydroxyl moieties.

Shalini Koshle

Sri Jayachamarajendra College of Engineering, India

Title: Screening of phytochemicals for the inhibition of JAK2 by molecular docking

Biography:

Shalini Koshle is a Senior Research Fellow in Department of Biotechnology, Sri Jayachamarajendra College of Engineering. She is currently pursuing PhD from Visvesvaraya Technological University, India. She has been awarded with Rajiv Gandhi National Fellowship, University Grant Commission, Government of India. She has published two papers in reputed journal and given oral presentation National Conference on “Technological Advancements in Chemical and Environmental engineering”.

Abstract:

Janus kinases-2 (JAK2) is a member of the Janus Kinase family and has been implicated in signaling by members of the type II cytokine receptor family. JAK2 is involved in the regulation of various pathways of cell growth, development, differentiation or histone modifications. Inhibition of JAK down-regulates phosphorylation of transcription factors known as STAT and blocks the JAK-STAT signaling pathway which is vital for tumorigenesis. In the present study molecular docking was carried out to elucidate the interaction of phytochemicals with Protein Kinase 2 domain for the inhibition of JAK2 to block cytokine signaling. PDB ID code 4C61 from the Protein Data Bank was used to retrieve JAK2 crystal structure at 2.45- A resolution and utilized for molecular docking under Schrodinger platform. Phytochemical, demethoxycurcumin from Curcuma longa as JAK2 inhibitor to modulate the JAK/STAT pathway. It is found that the phytochemical is potent to block the access at the site of Protein Kinase 2 domain. The efficacy was evaluated based on scoring function employed in Glide XP. Further ADME/ Tox studies validate the efficacy of the phytochemical to possess druggable like characteristics pertaining to standard drugs. Pharmacophore modeling of demethoxycurcumin showed binding energy with substitution of different R-groups.

Session Introduction

Masoud Sheidai

Shahid Behesti University, Iran

Title: Population genetic structure and species relationships in Senecio L. (Asteraceae, Senecioneae): Evidence from ITS, Cp-DNA and ISSR molecular

Biography:

MASOUD SHEIDAI has completed his PhD at the age of 28 years from Poona University India and Sabbatical studies from UBC University in Canada. He is now proffessor of Biology in Shahid Beheshti University, Tehran, Iran. He has published more than 125 papers in reputed journals and has been serving as an editorial board member of repute. Gene Conserve, and Bidiversity journals.

Abstract:

Senecio L. (Asteraceae, Senecioneae) is the largest genus of Asteraceae with about 1500 species and worldwide distribution and particularly in South Africa, Mediterranean floristic region and in temperate areas of Asia and America. Some species of Senecio have been transferred into the genus Iranecio-Four sections and 17 taxa including species and subspecies of this genus grow in Iran. In this work we studied the genetic variability and population structure of Senecio vernalis Waldst & Kit and species relationship of the genus based on ITS and Cp-DNA molecular markers. We studied 141 plant specimens of 16 geographical populations of Senecio vernalis. AMOVA and Gst analyses revealed the presence of extensive genetic variability within populations and significant molecular difference among the studied populations. Mantel test did not show significant correlation between genetic distance and geographical distance of the populations. This result indicates that gene exchange occurred between both populations that are far apart and between those that are in close vicinity. Structure and K-Means clustering revealed populations’ genetic stratification. CVA plot of populations based on morphological characters and ANOVA test showed morphological differences of the same populations. Consensus tree based on morphological and genetic data separated some of these populations from the others suggesting to have new varieties within this species. These results may be of use for future conservation and breeding of this important plant species. ITS and Cp-DNA phylogenetic tree of the species supported present taxonomic treatment of the genus and also agreed with exclusion of some taxa from this group. The evolution of the group and the species relationship will be discussed.

John Samuels

on Novel Solanaceae Crops, United Kingdom

Title: Bt Brinjal: a Case Study in Biosafety Risks to Plant Biodiversity

Biography:

J Samuels is an Independent Researcher and doing project on Novel Solanaceae Crops, at Penzance U.K.

Abstract:

Several transgenic disease-resistant crop forms have been developed for commercial use across the world. Most of these rely on genetic transformation brought about by genes substituted from the soil-borne microorganism Bacillus thuringiensis (“Bt”) which confer the ability to produce “Cry” proteins, which are lethal to arthropods such as lepidopterans. In the interests of biosafety, certain environmental risk assessments should be undertaken, so that the environmental consequences of commercial production can be determined. Such consequences include transgene transfer to related species of spiny solanums. If Bt transgenes become introgressed into these species the resultant hybrids may constitute a serious risk to plant biodiversity. This arises from the combination of pest resistance with the inherent weedy nature of this group. The resultant situation could generate aggressive weeds with a tendency to become invasive, particularly in the vicinity of farms in South and South-east Asia, on which Bt brinjal is cultivated. The implications for ecological equilibrium will thus present a threat to plant biodiversity. In order to make thorough assessments of these risks certain essential background information on the precise biological, taxonomic and floristic characteristics of the transformed species and its cultivated and wild relatives must be amassed. This should encompass information on: reproductive characteristics and phenology; interfertility relationships between the transformant and related species, as well as between the relatives themselves; correct nomenclature, identification and systematic placement; and floristics of wild relatives. Thorough and concise investigations of the possibility of transgene transfer to either (a) untransformed crops of the same species, (b) sympatric wild relatives, or (c) closely-related crops grown sympatrically, can thence be undertaken. The potential consequences for plant biodiversity of transgene transfer should not be underestimated, and detailed, long-term studies are vital for a balanced assessment of risks. The history of the development of Bt brinjal shows that, whilst certain studies have been of benefit, they have been limited in nature. An attempt is made here to contribute towards a fuller understanding of essential background information on Bt brinjal.

Session Introduction

Makobetsa Khati

CSIR Biosciences, South Africa

Title: Prospects of synthetic molecules in medicine

Time : 12:25-13:30

Biography:

Makobetsa Khati is Head of the Emerging Health Technologies Department at CSIR Biosciences. He is also an Honorary Research Associate in the Department of Medicine at Groote Schuur Hospital and the University of Cape Town. Makobetsa holds several degrees including a Master’s in Molecular Medicine from the Imperial College London, a Master of Public Health from the School of Public Health and Family Medicine, University of Cape Town, and a Doctorate in Molecular Pathology from the Sir William Dunn School of Pathology, University of Oxford.

Abstract:

Synthetic oligonucleotide molecules such as aptamers can be isolated in vitro against diverse targets including toxins, bacterial and viral proteins, virus-infected cells, cancer cells and whole pathogenic microorganisms. These synthetic molecules assume defined three-dimensional structures and generally bind functional sites on their respective targets. They possess the molecular recognition properties of monoclonal antibodies in terms of their high affinity and specificity. The applications of aptamers range from diagnostics and bio-sensing, target validation, targeted drug delivery, therapeutics, templates for rational drug design to biochemical screening of small molecule leads compounds. In this presentation, I will review recent progress made in the application of bio-medically relevant aptamers and relate them to their future clinical prospects.

Ravi K Birla

University of Houston, USA

Title: Recent advances in Cardiac tissue engineering

Time : 14:30-15:30

Biography:

Ravi Birla has completed his PhD from the University of Michigan, Ann Arbor and is currently with the Department of Biomedical Engineering at the University of Houston, where he also serves as Director of the Artificial Heart Laboratory. His research is in Cardiovascular Tissue Engineering and he has published over 40 peer reviewed scientific. He has extensive experience in the development of 3D models for heart muscle, blood vessels, tri-leaflet heart valves, heart pumps, bio-artificial ventricles and bio-artificial hearts. Dr. Birla holds several patents in the area of cardiovascular tissue engineering. He is also actively engaged in education and teaching related activities and has recently published a comprehensive textbook in the area of functional tissue engineering.

Abstract:

There has been an increase in the number of research papers describing the fabrication of 3D heart muscle models. Many different biomaterials have been used, several stem cell types have been used and many different bioreactor configurations have been evaluated. The first paper in the field of cardiac tissue engineering was published in 1997 and now 17 years later, we have made significant progress. In this discussion, I will review some of the recent advances in the field of heart muscle tissue engineering and discuss and describe some of the more significant advances. Furthermore, I will also highlight many of the scientific and technological hurdles that need to be overcome in order to move the field of cardiac tissue engineering forward. I will use examples from the Artificial Heart Laboratory (AHL) at the University of Houston.

Chair

Ravi K Birla

University of Houston, USA

Co-Chair

Makobetsa Khati

CSIR Biosciences, South Africa

Session Introduction

Robert J Schwartz

University of Houston, USA

Title: Conversion of adipogenic mesenchymal stem cells into mature cardiac myocytes

Time : 15:30-16:00

Biography:

Robert J. Schwartz, PhD is a Professor in the Department of Biology and Biochemistry and the Director of the Center for Molecular Medicine and Experimental Therapeutic. He previously was at Baylor College of Medicine in Houston, where he served as a tenured professor in the Departments of Cell Biology, Molecular and Cellular Biology, Medicine, and Molecular Physiology. He also was co-director of the Baylor College of Medicine Center for Cardiovascular Development. Schwartz also spent five years at the Institute of Biosciences and Technology where he was the Director of the Institute. During his more than thirty five years in Houston, Schwartz became widely recognized for his research on the developmental and genetic aspects of congenital heart disease. In this field he has received eleven US patents and co-founded three companies. He earned his B.S. from Brooklyn College and his PhD in Biology from the University of Pennsylvania.

Abstract:

ETS2 and MESP1 first used to convert human foreskin fibroblasts also, converted human adipogenic mesenchymal stem cell (hADMSCs) into cardiac progenitors (CPCs). These factors up regulated cardiac mesoderm cell surface markers, such as KDR, PDGFRa, and CXCR4 and a cadre of cardiac regulatory factors, but without the appearance of many calcium handling proteins. We then explored the role of 3D cardio-spheroids formed in a rotating Synthecon bioreactor that mimics microgravity on earth. Without the addition of any other reagent or drug we observed the robust induction of adult myosin heavy chains, contractile sarcomeres, ion channels, calcium handling channels and pumps in 3D cardio-spheres. We began to decode the gene expression network of ion channels, SR and t-tubules genes using cutting edge genetic informatics on the ground experiment and found that hypoxic signaling likely coordinates the appearance of many genes involved with calcium handling and myocyte maturation. Our experimental paradigm contributes to a novel regenerative strategy that enhanced myocyte maturation from converted human mesenchymal stem cells.

Vsevolod V. Gurevich

Vanderbilt University, United States

Title: Engineering signaling-biased arrestins for targeted regulation of cell behavior

Time : 16:00-16:30

Biography:

Vsevolod V. (Seva) Gurevich has completed his PhD in 1989 from Shemyakin Institute of Bioorganic Chemistry, Moscow, Russia, and postdoctoral training (1991-5) in the laboratory of Dr. J.L. Benovic, Thomas Jefferson University, Philadelphia, PA. He is Professor of Pharmacology at Vanderbilt University. He has published more than 160 papers in reputed journals and has been serving as an editorial board member of several journals.

Abstract:

Arrestins specifically bind active phopshorylated GPCRs, blocking further G protein activation and orchestrating G protein-independent signaling. Based on the elucidation of arrestin structure and key functional elements we constructed special arrestins to channel cell signaling in desired direction. We designed enhanced phosphorylation-independent arrestin-1 mutants and showed that they can compensate for the defects of rhodopsin phosphorylation in vivo. We identified the residues on the receptor-binding surface of non-visual arrestins that determine their preference for particular GPCRs. Based on this information we created arrestin-3 mutants with high receptor specificity by a few substitutions. We designed arrestin-3 mutant that suppresses JNK activation in the cell. We found that caspase-cleaved arrestin-2 facilitates apoptotic cell death, whereas its caspase-resistant mutant protects the cells. We also identified a small element of arrestin-3 that acts as a mini-scaffold, promoting JNK activation in vitro, in cells, and in the brain in vivo. Arrestins play a role in numerous signaling pathways and physiological processes. Therefore, targeted mutagenesis can yield arrestin-based molecular tools to tell the cell what to do in a language it cannot disobey.

Masoud Sheidai

ShahidBehesti University, Iran

Title: Olive biotechnology: The assessment of tissue culture induced genetic variability in olive (Oleaeuropaea) by molecular markers

Time : 16:50-17:20

Biography:

Masoud Sheidai has completed his PhD at the age of 28 years from Poona University in India and Sabbatical studies from UBC University in Canada. He is now proffessor of Biology in Shahid Beheshti University, Tehran, Iran. He has published more than 125 papers in reputed journals and has been serving as an editorial board member of repute. Gene Conserve, and Bidiversity journals.

Abstract:

Olive is one of the most important tree crops of the country and it is cultivated in many places. Propagation of true to type olive plants is important for many olive companies and farmers in the country and for this reason genetic analysis of randomly selected tissuebculture regenerated olive plants of cultivars Kroneiki, Zard, Roughani and X was performed and compared with the mother plant. We used Cp-DNA and RAPD molecular markers to check genetic fidelity versus somaclonal variation. Both RAPD and Cp-DNA analyses revealed that some of the regenerated plants differed extensively in their genetic content. These plants were placed in different clusters far from the mother plants in NJ tree and TNT tree obtained from these two molecular markers. We identified also some regenerated plants that were true to types of the mother plants. Th ese plants also diff ered in their morphological features. Genetic and morphological changes were more extensive with increase in subculture numbers. Different uses of these two types of plants will be discussed.

JEEVITHAN ELANGO,

Shanghai Ocean University, China

Title: Characterization of Type-II Fish collagen extracted from Shark cartilage and its potential effect on Rheumatoid arthritis

Biography:

Jeevithan was working as PA and SRF for four year in various research project mainly focusing on “purification and fractionation of active compounds from medicinal plants, mRNA based RT-PCR assay detection of viable pathogens, development of RFLP method for fish authentication and Fish gelatin, collagen films and scaffolds” in India. Then, he joined doctorate at Department of Marine pharmacology, College of Food Science and Technology, SHOU, China in 2013. Up to now, he has published 17 research papers in reputed journals. His current research is focused on the characterization of type-II collagen from different shark cartilages and its potential uses to treat rheumatoid arthritis.

Abstract:

Type-II pepsin soluble collagens (PSC) were isolated from cartilage of shark; and examined for their biochemical and antioxidant properties. The purified collagen was composed of an identical (α1)3 chains. The biochemical properties such as viscosity, solubility, amino acid composition, glycoprotein content, SEM, FTIR, CD and DSC spectra; and antioxidant properties substantiated that PSC could be used as a suitable biomaterial for pharmaceutical and biomedical industries as an alternative source of mammalian collagen. From the gut-sac (in-vitro intestinal absorption) experiments, we identified hydrolysates within a MW range from 70 kD to 8 kD on the serosal side of the intestine after the application of collagen hydrolysates and a significant amount of collagen hydrolysate is absorbed in the molecular form of 35-40 kDa. In continuation, type-II collagenous polypeptide (37 kDa) was successfully separated from the hydrolysates and studied for their physico-functional and antioxidant properties. Further, we target to confirm the effects of oral tolerance of PSC on inflammatory and immune responses to the ankle joint of rheumatoid-arthritis (RA) rats induced by Complete Freund’s Adjuvant. The immunological indexes such as delayed type hypersensitivity, IL-10 and T cell apoptosis showed that PSC with concentration of 10 μg/L could have significant effect in the model. The result of histological staining indicated that the recovery of the articular membranes of ankle joint in PSC group was greatly enhanced. In conclusion, the present results suggest that appropriate dose of PSC can not only ameliorate symptoms but also modify the disease process of RA.

Session Introduction

Ravi K. Birla

University of Houston, Houston, United States

Title: Tissue and Organ Fabrication for the Heart

Biography:

Ravi Birla has completed his PhD from the University of Michigan, Ann Arbor. He is currently with the Department of Biomedical Engineering at the University of Houston, where he also serves as Director of the Artificial Heart Laboratory. His research is in Cardiovascular Tissue Engineering and he has published over 40 peer reviewed scientific papers and also a recent textbook in the area.

Abstract:

Treatment of cardiovascular disorders remains a major medical challenge. Pharmacological interventions, mechanical assist devices and heart transplantation have provided life saving options. While heart transplantation has been the most successful treatment modality for end stage heart failure, chronic shortage of donor organs has limited widespread applicability. Tissue engineering has tremendous potential to provide alternative treatment modalities that could help alleviate the donor heart crisis. Cardiac tissue engineering strategies are focused on the development of functional 3-dimensional (3D) patches, fabricated by culturing cells within a natural or synthetic scaffold. Applied to a clinical scenario, 3D heart muscle could be sutured onto the surface of injured left ventricular tissue to support/augment contractile function. Research at the Artificial Heart Laboratory (AHL) is focused on the development of 3D cardiovascular tissue constructs. We have projects focused on the development of heart muscle, blood vessels, tri-leaflet valves, cell based cardiac pumps, bioartificial ventricles and hearts. In addition, we have projects focused on supporting technologies. These include perfusion systems to support long-term culture and bioreactors for electromechanical stimulation. During the past several years, we have developed the building blocks required for the fabrication and culture of cardiovascular tissue constructs – in this presentation, we will provide an overview of platform technology required to bioengineer functional 3D cardiovascular tissue constructs.

Seyed Abdolreza Mortazavi Tabatabaei

Tehran University of Medical Sciences, Iran

Title: Adipocyte derived mesenchymal stem cell supports keratinocyte growth in a modified collagen-hyalorunic acid matrix

Biography:

SA Mortazavi Tabatabaei has completed his Medical doctorate at the age of 25 years from Tehran University of Medical Sciences and hid PhD at the age of 40 years from Shahid Beheshti University School of Medicine. He is the scientific member of Cell Therapy department in School of Advanced Technologies in Medicine. He has published more than 20 papers in ISI journals and has been serving as an editorial board member of some medical journals.

Abstract:

Skin loss can occur due to many reasons including burns, diabetic wounds, venous ulcers, trauma, genetic disorders and etc... . Although much progress has been made towards the development of skin engineering but these are not completely efficient and require to improvement. It is known that many types of cells including fibroblasts and bone marrow stem cells improve performance of composite skin substitutes. Secretion of collagen matrix and epidermal differentiation takes place after mesenchymal epithelial communication. Development of the better transplantable dermal layers that support keratinocyte proliferation is very important for therapeutic option. Here we worked on an autologous construct as a successful skin substitute by culture of human Adipocyte Derived Mesenchymal stem cells (hADMSC) and human keratinocytes on the Hyalorunic acid-Collagen matrix. Bi-layer skin culture was generated by using biodegradable Hyalorunic acid-Collagen matrix. To analyze the effects of the hADMSC on the epithelial regeneration, keratinocytes were seeded onto the hADMSC-populated matrix and cultured at 37°C, in a 5% CO2 and 20% O2 humidified atmosphere. First, 106 hADMSC were seeded onto the matrix and cultured for 3 days in the basal medium. Then, keratinocytes were overlaid on the hADMSC and cultured for other 7 days in complete keratinocyte medium. We have evaluated the growth behavior of hADMSC and keratinocytes as a co-culture on the Col-HA layer. The obtained results revealed that the designed co-culture has a high potential for human keratinocyte proliferation. Keratinocytes without ADMSC-support formed only an irregular layer. This suggests that mesenchymal intercellular communications are necessary for proliferation and stratification of human keratinocytes. Keratinocytes cultured with hADMSC expressed Ck10 and Ck14 in supra-basal layer. However ADMSC is not a part of normal skin but it could promote the epidermal regeneration as describes previously for the bone marrow stem cell and other progenitor cells. Our data propose ADMSC as an efficient and safe source of feeder cells for the generation of keratinocyte autografts without immunological complications.

Session Introduction

Jin Wang

Stony Brook University, United States

Title: The landscape and flux theory for biological networks

Biography:

Dr. Jin Wang is a Professor of Chemistry and Physics at Stony Brook University. He has finished B.S., (Physics) in year of 1984 at Jilin University China. He has done his Ph.D. in Astrophysics from University of Illinois and held the position of Post Doctor Research Associate (Chemistry and Biological physics), from 1991-1996, University of Illinois. He worked as a Guest Scientist at National Institutes of Health and was the Vice President and Senior Analyst at Citibank from 1997-2005. He also holds the position of Adjunct Professor (Physics and Credit Management), at Jilin University, China and Changchun Institute of Applied Chemistry, Chinese Academy of Science. He is also an Adjunct Professor in the departments of Applied Mathematics and Harriman College of Business, at SUNY Stony Brook. He had previously worked as an Adjunct Professor (Chemistry), SUNY Stony Brook during 1999-2004. He was awarded with National Science Foundation Career Award in 2005. He is a fellow of American Physical Society and American Association for the Advancement of Science.

Abstract:

We developed a landscape and flux theory for biological networks. We identify the two global driving forces for biological network. One is the gradient of the underlying landscape and the other is from the curl flux. The underlying landscape is linked to the steady state probability distribution and provides a global picture for describing the networks. We found that the landscape can be used to quantify the global stability and robustness of the system. The non-zero flux breaks the detailed balance and therefore gives a quantitative measure of how far away the system is from the equilibrium state, reflecting the degree of the energy input to the system. Our decomposition of the driving forces of the complex systems into landscape gradient and curl flux establishes the link between the dynamics and the underlying thermodynamic non-equilibrium natures. We applied our theory to several biological systems such as cell cycle, stem cell differentiation and reprograming, cancer. For cell cycle oscillations, we found the underlying landscape has a Mexican hat ring shape topology. The height of the center island Mexican hat determines the global stability. The landscape gradient attracts the system down to the oscillation ring. The curl flux is the driving force for coherent oscillation on the ring. Along the cell cycle oscillation ring there are a few basins of attractions which can be identified and quantitatively described as the G1, SG2 and M phases. The barriers between these local basins become the check points of the cell cycle. The speed of the cycle is determined by the flux originated from nutrition and the barriers at the check points between the basins. Global sensitivity analysis on these two global factors gives us information on key genes and regulations determining the function. From this, new anti-cancer strategy can be designed aiming at reducing the speed of the cell cycle. We also applied our landscape and flux theory to stem cell differentiation and development. We quantify the Waddington landscape for differentiation and identify the stem cell and differentiation basins of attractions. We quantify the differentiation and reprograming path for a human embryonic stem cell network and identify the key genes and regulations. We also constructed a cancer gene network and quantify the landscape for cancer where we identify the normal, cancer and apoptosis basins of attractions. We quantify the major pathways of cancerization and identify the key genes and regulations responsible.

Makobetsa Khati

CSIR Biosciences, South Africa

Title: Synthetic RNA molecule mitigates HIV-induced apoptosis of cardiomyocytes and also prevents HIV infection

Biography:

Makobetsa Khati is Head of the Emerging Health Technologies Department at CSIR Biosciences. He is also an Honorary Research Associate in the Department of Medicine at Groote Schuur Hospital and the University of Cape Town. Makobetsa holds several degrees including a Master’s in Molecular Medicine from the Imperial College London, a Master of Public Health from the School of Public Health and Family Medicine, University of Cape Town, and a Doctorate in Molecular Pathology from the Sir William Dunn School of Pathology, University of Oxford.

Abstract:

Chronic HIV infection causes a broad range of clinical complications, some of which remain poorly understood. One such complication is HIV-associated cardiomyopathy (HIVCM). In this study, we evaluated a novel approach to mitigate HIVCM using synthetic RNA molecules called aptamers. Specifically, we used a shortened synthetic derivative of anti-gp120 aptamer called UCLA1. The aptamer protected cardiomyocytes from HIV induced apoptosis. Furthermore, the aptamer also prevented infection of human macrophages and CD4+ T cells by a broad range of clinical isolates of HIV-1 from different subtypes. Taken together, these data argue in favour of further development of this RNA synthetic molecule to prevent HIV infection in uninfected individuals, and also to mitigate AIDS pathogenesis such as HIVCM in already infected individuals.

Abhinav Grover

Jawaharlal Nehru University, India

Title: N-QCCA-Novel fragment-based QSAR modeling and combinatorial design of pyrazole derived CRK3 inhibitors as potent anti-leishmanialsN-QCCA-Novel fragment-based QSAR modeling and combinatorial design of pyrazole derived CRK3 inhibitors as potent anti-leishmanials

Biography:

Abhinav Grover has completed his PhD at the age of 26 years from Indian Institute of Technology Delhi (IITD) and Postdoctoral studies from IITD and Jawaharlal Nehru University (JNU). He is currently working as Assistant Professor in School of Biotechnology, JNU. He has published more than 40 papers in reputed journals and has been serving as Reviewer of a plethora of reputed journals. He has been awarded with various national and international honors, distinctions and awards.

Abstract:

The CRK3 cyclin-dependent kinase of Leishmania plays an important role in regulating the cell cycle progression at the G2-M phase checkpoint transition, proliferation and viability inside the host macrophage. In this study, a novel fragment based QSAR model has been developed using 22 pyrazole derived compounds exhibiting inhibitory activity against Leishmanial CRK3. Unlike other QSAR methods, this fragment based method gives flexibility to study the relationship between molecular fragments of interest and their contribution for the variation in the biological response by evaluating cross-term fragment descriptors. Based on the fragment-based QSAR model, a combinatorial library was generated and top two compounds were reported after predicting their activity. The QSAR model showed satisfactory statistical parameters for the dataset (r2=0.8752, q2=0.6690, F-ratio=30.37 and pred-r2=0.8632) with four descriptors describing the nature of substituent groups and the environment of the substitution site. Evaluation of the model implied that electron-rich substitution at R1 position improves the inhibitory activity while decline in inhibitory activity was observed in presence of nitrogen at R2 position. The analysis carried out in this study provides a substantial basis for consideration of the designed pyrazole-based leads as potent anti-leishmanial drugs.

Hail Rihan

Damascus University, Syria.

Title: An effective system for a better understating of plant cold tolerance

Biography:

Dr Hail Rihan, (PhD plant biotechnology) is a lecture at Damascus University (Syria) and the leader of “Molecular Summer School with Plymouth University” programme in the UK. Dr Rihan has a significant number of publications in international journals and conferences. Two of Dr. Rihan publications have been reviewed and featured in Agricell Reports and one featured on Earth Emphasis website. Dr Rihan is a holder of Plymouth Award certificate in recognition of student achievements outside the curriculum. He acted as an expert in fruit tree production in the Arab Centre for Studies of Arid Zones and Dry Lands (ACSAD) 2007-2008. Dr Rihan was the Winner of the Early Career Researcher Award in the Expert category in the Vice-Chancellor’s Enterprise Awards 2012 at Plymouth University. Dr Rihan has chaired and organized over 8 national and international conferences and workshops in the UK.

Abstract:

An effective protocol for cauliflower micropropagation was developed by Rihan et a (2011) and enables the production of thousands of microshoots per cauliflower curd and provides an optimal system for the analysis of the physiological and molecular responses of cauliflower to various types of abiotic stresses. Moreover, these microshoots can be used for artificial seed production, which are required to show a high level of abiotic stress tolerance in order to be a cost effective method for cauliflower propagation. Molybdenum (Mo) was used in this study to improve the cold tolerance of cauliflower microshoots/artificial seeds. The capacity of Mo to up-regulate CBF/DREB1 in cauliflower microshoots was confirmed. The study could help in improving the understanding of the abiotic stress network in plants and in improving the quality and efficiency of cauliflower artificial seed production systems.

Session Introduction

Ruchi Singla

Chandigarh Group of Colleges, India

Title: Biosensors - A promising alternative to improve the agricultural sector of an Indian economy

Biography:

Ruchi Singla is a Professor & Head of the department for the electronics and communications at Chandigarh Group of Colleges, Mohali, India.

Abstract:

Green Revolution plays a crucial rule in replacing the trends of ancient agricultural practices with the modern agricultural tools to increase productivity and prevention of crops against diseases by different types of pests. Increased needs enhance the usage of chemicals also termed as Pesticides in different parts of the world that can produce toxic effects. These Chemicals enter into the atmosphere through air, water, soil and through the food chain. Owing to their indiscriminant and excessive use over the crops, their detection and analysis is of prime concern today. Conventionally, chromatographic and spectroscopic methods are employed for determining their presence to prevent contamination of environment against their alarming effects. These techniques are highly expensive, laborious and time consuming. This immediate need leads to the development of biosensors as a promising alternative over conventional ones for detection of pesticides. Biosensors consist of Biorecognization element and transducer part. We can classify them either on the basis of input recognization element or on the basis of methods employed to convert the signal into the usable form like electrical, Optical or Fluorescence based. In this paper, we introduce novel ways for the development of transducers classification for antibody based input biorecognization element biosensors upon the certain types of pesticides that are much harmful and creates irreversible effects. The success of the use of Biosensors lies in their uniqueness to interface the biological element with transducer component and senses for the specific analyte. The Biosensors specifically combines the property of biological elements with the physical transducer. The type of transducer employed depends upon the concentration of analyte in the sample. With their efficient use, alarming effects of different pollutants can be controlled. The contribution of Biosensors to the agricultural sector is really amazing

Kerstin Otte

University of Applied Sciences Biberach, Germany

Title: Synthetic microRNAs to boost cellular production of biopharmaceuticals

Biography:

Kerstin Otte is a trained biologist trained from the Phillipps-University of Marburg, Germany and obtained her PhD at the SL-University in Uppsala, Sweden. After a postdoctoral fellowhip at the Gurdon Institute at Cambridge, UK, she gained industry experience as senior scientist at Graffinity Bioscience and LION Bioscience, both Heidelberg, Germany, in preclinical drug development. Since 2006 Kerstin Otte holds a professorship for molecular and cell biology at the University of Applied Sciences Biberach, Germany, at the Faculty of Pharmaceutical Biotechnology. Her research focusses on cell line development for the production of biopharmaceuticals.

Abstract:

Recently, microRNAs (miRNAs) have been discovered as innovative instruments for cell engineering of biopharmaceutical production cells to minimize existing bottlenecks of eukaryotic expression systems. As small non-coding RNAs, miRNAs do not add any translational burden to the cell and several miRNAs can be exploited in parallel as polycystronic clusters thereby acting concertedly to regulate hundreds of different target genes and regulate entire pathways within the cell. miRNAs are involved in virtually all cellular processes such as apoptosis, proliferation, development or protein biosynthesis. The revelation of the Chinese hamster ovary (CHO) genome and transcriptome as well as the CHO miRnome substantially accelerated miRNA research in this industrially relevant cell type. To elucidate miRNA function and usability as engineering tools in recombinant CHO cells, we performed a genome-wide high-content miRNA screen assaying for phenotypic changes regarding productivity, cell proliferation, viability, necrosis and apoptosis. Among many novel ‘engimiRs’ which have been found within the screen we discovered a whole miRNA family to strongly contribute to enhanced protein production in CHO cells. Stable overexpression gave rise to superior cell lines outperforming the parental cell line. Moreover, detailed analysis of screening data revealed a novel redundant mechanism of action for miRNAs in eukaryotic cell systems. Our results highlight the application of miRNAs as powerful tools for cell engineering and will shed additional light on these tiny but mighty regulators of gene expression.

Session Introduction

Nicolas Mermod

University of Lausanne, Switzerland

Title: DNA Recombination Engineering for Improved and More Reliable Protein Expression from DNA Vectors

Biography:

Nicolas Mermod is Professor of Biotechnology at the Faculty of Biology and Medicine of the University of Lausanne, and a co-founder of Selexis SA, a biotech company. Nic completed his PhD at the University of Geneva in environmental biotechnology, followed by post-doctoral studies at the University of California at Berkley, USA, with Professor Robert Tjian. Nic then joined the University of Lausanne as an Assistant Professor, to become full Professor and the director of the Institute of Biotechnology. Nic’s Laboratory for Molecular Biotechnology at EPFL, which gained recognition in the field of gene expression in eukaryotic cells by publishing over 100 papers in peer reviewed renowned journals. Besides his scientific publications, Nic has authored a number of patents on epigenetic regulatory elements and gene transfer.

Abstract:

Epigenetic regulatory DNA elements can be added to expression vectors to increase transgene genomic integration, to dampen silencing, and to provide overall a more reliable expression in cultured mammalian cells. Nevertheless, expression remains variable from one cell clone to the next. We have sequenced the genomes of CHO cell clones expressing recombinant proteins, yielding information on the molecular mechanisms that allowed the genomic integration of the plasmid vectors. This provided an approach to transiently silence unwanted recombination pathways, so as to favor a microhomology-based recombination mechanism that mediates integration into expression-permissive genomic loci. When combined to MAR epigenetic regulatory elements, this provides much more predictable and homogeneous levels of transgene expression in polyclonal cell populations expressing a gene of interest.

Renata Silva-Mann

Universidade Federal de Sergipe, Brazil

Title: Genaplant - Genetic parameters as tools for selection of indicators of sustainability, diversity and recognizing new native plant genotypes for industrial use

Biography:

Renata Silva-Mann is professor at the Universidade Federal de Sergipe (UFS), has completed his PhD at Universidade Federal de Lavras (UFLA), and attended sandwich program in Brigham Young University (BYU) and postdoctoral studies at the Wageningen University Research (WUR). She is the director of division of Biosafety at UFS. She has published more than 60 papers in reputed journals and has been serving as an editorial board member of repute.

Abstract:

There is growing interest in defining indicators of sustainability, which are important for monitoring the conservation of native forest, particularly in areas of permanent protection. These indicators are references for assessing the state of the forest and the status of the depredated area and its ability to maintain species populations. The aim challenge is to select genetic parameters as indicators of sustainability for native forest species in fragments located in riparian areas in Brazil. This study was carried out using the indicators suggested by the Organization for Economic Cooperation and Development, which were identified as Driving-Pressure-State-Impact-Response (DPSIR) factors. The genetic parameters were obtained by DNA molecular markers analysis in populations located in different biomes in Brazil. The framework for species conservation suggests 17 indicators of sustainability. In accordance with genetic parameters, the populations could be isolated, and these genetic parameters can be used to monitor the sustainability of those populations with the aim of defining strategies for forest restoration and to select ecotypes for industrial use.

Petros Kolovos

Erasmus University Medical Center based in Rotterdam, Netherlands

Title: Targeted chromatin capture (T2C), a new method to unravel the local spatial organization of the genome at a single restriction fragment resolution

Biography:

Petros Kolovos has done PhD. In Molecular and Cell Biology at The Erasmus University Medical Center based in Rotterdam, Netherlands.

Abstract:

The last years have been a significant effort to unravel the spatial organization and the chromatin interactions of the genomes. Towards that objective, chromosome conformation capture technology and its derivatives contributed significantly. However, the need of a technique, which is affordable for most of the people and at the same time interrogates large selected regions of the genome, has become quite apparent. Furthermore, the borders of the topological associated domains (TADs) as well as the interactions within and between TADs can not been identified in an adequate manner with the usual resolution (40kb) of Hi-C. For that reason we have developed a method termed Targeted Chromatin Capture (T2C) [1]. It provides a genome wide analysis of a selected region of the genome at high resolution (single restriction fragment resolution, from 2 to 6 kbp) at low cost due to the lower sequencing effort (1/5 up to 1/13 of a Illumina based sequencing lane). TADs and their respective boundaries can be identified accurately due to the significantly improved resolution. All the interactions within and between TADs can be observed with T2C, because every restriction fragment can serve as a ‘viewpoint’ and all their interactions, both cis or trans, can be identified. Thus multiple 3C-seq, 4C-seq or 5C experiments do not have to be performed. We have used T2C for different loci and identified the same topological domains and chromatin interactions which have been observed before. Furthermore, with T2C we can answer the perpetual question of the actul structure of the genome and which model is the most prominent. Hence, T2C can be used as an affordable, cost-effective, diagnostic tool with single restriction fragment resolution to explore the local spatial organization of the genome, chromatin interactions and unravel the 3D structure without requiring laborious procedures or massive sequencing efforts.

Chidananda Nagamangala Kanchiswamy

Research and Innovation Centre, Italy

Title: Non-GMO genetically edited crop plants

Biography:

Chidananda Nagamangala Kanchiswamy did a PhD at the University of Turin in Torino (Italy), He spent most of his PhD research at Max Planck Institute for chemical ecology Jena and Center for Ecological Research Institute, Kyoto University (Japan) He now works as a postdoc (Marie Curie COFUND postdoc incoming 2010) at Foundation Edmund Mach, San Michele all'Adige, Trento, Italy, investigating on two exciting projects, 1) microbial volatile organic compounds perception, signal transduction and their effect on model and crop plants and 2) Next generation genome editing tools for fruit crop improvements.

Abstract:

The availability of genome sequences of many crop plants accompanied with revolution of new genome editing tools provided a breakthrough in modulating novel traits with unprecedented control and accuracy. However, plasmid mediated delivery of these genome editing components into cells can results in uncontrolled, random integration of plasmid sequences, potential safety problems, possible GMO regulations and other social hurdles. Here, we would like to propose direct delivery of purified Cas9 protein with guide RNA into plant cells. This method has shown high efficiency, significantly reduced off-target effects, and immediate genome editing after delivery compared to plasmid mediated genome editing. Furthermore, Cas9 protein-guide RNA complexes will be decomposed immediately after editing the gene of interest and thus there is huge possibility to be considered as Non-GMO crop plants.

Session Introduction

Vitaly K Koltover

Russian Academy of Sciences, Russia

Title: Theory of reliability in systems biology: Reliable systems from unreliable elements

Biography:

V.K. Koltover has completed his PhD (Physics and Math – Chemical Physics) at the age of 27 years from Institute of Chemical Physics, USSR Acad. Sci., Moscow, and his ScD (Biology – Biophysics) at the age of 44 from Highest Attestation Committee, Moscow (fSU). He is Head Researcher in Institute of Problems of Chemical Physics, RAS, Chernogolovka, Moscow Region. He has published more than 200 papers in reputed journals and has been presenting his papers at international meetings in Russia, Austria, Canada, China, France, Germany, Greece, India, Israel, Italy, Japan, Ukraine and USA.

Abstract:

Biological systems perform their functions in the presence of a great number of random factors which disturb all functional strata. Therefore, similarly to technical devices, they are not perfectly reliable in operation. The field of systems biology and biophysics in dealing with the problem of reliability, incorporates the theoretical and experimental investigations of quantitative characteristics and mechanisms of failures and renewal processes. It also includes elaboration of methods for testing reliability and predicting failures in biological systems. The reliability problems are closely related with aging and the problems of resistance of biosystems to deleterious environmental factors including ionizing radiation. The regular conferences which were initiated to deal with the problem of reliability of biological systems starting from 1975 in the former USSR have given a strong impetus to research in this direction. It has also spurred the similar studies on reliability of biological systems (under the style of “Robustness”) on the other side of the former "Iron Curtain". In this report, to illustrate the ideas of the reliability trend, I present the results of application of the systems reliability approach to the problem of aging. The approach is based on the simple general principles that all biomolecular constructions are designed in keeping with the genetic programs in order to perform the programmed, preset functions; all of them operate with the limited reliability; the timely replacement or prophylaxis of unreliable functional elements i.e., the metabolic turnover is the main line of assuring the high systems reliability and there is a finite number of critical elements which perform the supervisory functions over the preventive maintenance but these “Supervisors” also operate with the limited, preset and reliability. On this basis, the universal features of aging such as the exponential growth of mortality rate with time and the correlation of longevity with the species-specific resting metabolism are naturally explained. The stochastic malfunctions of the mitochondrial electron transport nanoreactors that produce the superoxide radical (О2•–), seem to be of first importance. Basing on the reliability-theory approach, one can estimate that the longevity of human brain could reach 250 years should the antioxidant defense against the free-radical failures be perfect. Thus, aging inevitably occurs as the consequence of the programmed, genetically preset, deficiency in reliability of the biomolecular constructions while the free-radical timer serves as the effective stochastic mechanism of realization of the program. Furthermore, the systems reliability approach provides heuristic methodology for novel preventive medicine including novel radiation protectors based on the stable magnetic isotopes.

De Storme Nico

University of Ghent, Belgium

Title: MALE APOMIXIS - Towards the synthetic engineering of clonal seed formation in plants

Biography:

Nico De Storme obtained his Master Degree in Bioscience Engineering - Agricultural Sciences at the University of Ghent - Belgium in the year 2006. During his PhD (FWO grant) he focused on the identification of genetic and environmental factors underlying 2n gamete formation in plants. After completing his PhD at the Department of Plant Production in 2013, he received an FWO PostDoc scholarship to continue his research on the regulation of meiotic recombination and (a)sexual reproduction in plants. Nico has published more than 15 papers in high-ranking peer-reviewed A1 journals, including Plant Physiology and The Plant Cell.

Abstract:

Apomixis is a specialized form of plant reproduction, in which clonal seeds are formed through a short-circuiting of the female sexual pathway. Due to its ability to fix genotypes over successive generations, apomixis is considered the holy grail for plant breeding, particularly in the view of hybrid fixation and polyploid stability. Although apomixis is a natural occurring phenomenon, it has not been retrieved in major crop species. Hence, current research is focused on the genetic engineering of apomixis and on the identification of genes that underlie its major developmental components, including female apomeiosis and parthenogenesis. Here, we present an alternative method to genetically engineer clonal seed formation in plants; namely ‘male apomixis’. Basically, in this process, male meiosis is converted into a mitotic division and resulting clonal pollen are used to fertilize eggs that selectively eliminate their own genome input. In plants, parent-specific genome elimination (GE) can be obtained by uniparental alterations in the centromeric chromatin status (CENH3). Male apomeiosis, on the other hand, can be achieved by eliminating both meiotic recombination and reductional cell division, as for example by the combined loss of AtSPO11-1 and JAS. By using resulting 2n atspo11-/-jas-/- pollen in the fertilization of a GE line we obtained diploid progeny plants genetically identical to the pollen donor. Although the efficiency of clonal seed formation is rather low, these findings demonstrate that the combined loss of two genes can confer male apomeiosis and hence provides a molecular basis for the synthetic engineering of ‘male apomixis’ in plants.

Tsige Ketema

Jimma University, Ethiopia

Title: Incidence of Severe Malaria Syndromes and Status of Immune Responses among Khat Chewer Malaria Patients in Ethiopia

Biography:

Tsige Ketema has completed her MSc degree in Biomedical Sciences from Addis Ababa University at the age of 29 years. She has published more than 15 articles in reputable journals and currently working as Associate professor, researcher, and a PhD fellow at Jimma University, Ethiopia.

Abstract:

Although more emphasis has been given to the genetic and environmental factors that determine host vulnerability to malaria, other factors that might have a crucial role in burdening the disease have not been evaluated yet. Therefore, this study was designed to assess the effect of khat chewing on the incidence of severe malaria syndromes and immune responses during malaria infection in an area where the two problems co-exist. Clinical, physical, demographic, hematological, biochemical and immunological data were collected from Plasmodium falciparum mono-infected malaria patients (age ≥ 10 years) seeking medication in Halaba Kulito and Jimma Health Centers. In addition, incidences of severe malaria symptoms were assessed. The data were analyzed using SPSS (version 20) software. Prevalence of current khat chewer malaria patients was 57.38% (95%CI =53-61.56%). Malaria symptoms such as hyperpyrexia, prostration and hyperparasitemia were significantly lower (P<0.05) among khat chewer malaria patients. However, relative risk to jaundice and renal failure were significantly higher (P<0.05) in khat chewers than in non-khat chewer malaria patients. Longer duration of khat use was positively associated with incidence of anemia. IgM and IgG antibody titers were significantly higher (P<0.05) among khat chewer malaria patients than among malaria positive non-chewers. Although levels of IgG subclasses in malaria patients did not show significant differences (P>0.05), IgG3 antibody was significantly higher (P<0.001) among khat chewer malaria patients. Moreover, IgM, IgG, IgG1and IgG3 antibodies had significant negative association (P<0.001) with parasite burden and clinical manifestations of severe malaria symptoms, but not with severe anemia and hypoglycemia. Additionally, a significant increment (P<0.05) in CD4+ T-lymphocyte population was observed among khat users. Khat might be an important risk factor for incidence of some severe malaria complications. Nevertheless, it can enhance induction of humoral immune response and CD4+ T-lymphocyte population during malaria infection. This calls for further investigation on the effect of khat on parasite or antigen-specifc protective malaria immunity and analysis of cytokines released upon malaria infection among khat chewers.

Session Introduction

Soumendra Rana

Indian Institute of Technology Bhubaneswar, India

Title: Structural modeling of C5a receptor: molecular insights into agonism and antagonism

Biography:

Soumendra Rana has completed his PhD at the age of 29 years from IIT Bombay and postdoctoral studies from Washington University School of Medicine in St. Louis, including University of Arizona, Tucson. He is currently an assistant professor (Chemistry and Biosciences) at the IIT Bhubaneswar, one among the 14 premier technical institutes of the country. He has published more than 12 papers in reputed journals and has been serving as an editorial advisory board member in International Journal of Chemical and Pharmaceutical Review and Research.

Abstract:

The complement component fragment 5a receptor (C5aR), also known as the anaphylatoxin receptor is one of the two major G-protein coupled receptor (GPCR) that demonstrates a high affinity interaction with C5a, the most potent proinflammatory polypeptide of the complement system, known for its pleiotropic effects in both immune and non-immune cells. No wonder, the C5a-C5aR interaction has been tagged druggable for discovery of targeted therapeutics.1 However, the molecular basis of agonism or antagonism in C5aR is yet to be established clearly, largely due to the unavailability of a structure of C5aR. In addition, while the role of allosterism in C5aR is discussed in the literature, it is completely unheard for C5a, a potential drug target that modulates the downstream signaling of C5aR. It not only hinders the discovery and development of new lead molecules, but also affects the rational optimization of the known lead molecules as potential therapeutics, targeting the C5a-C5aR signaling axes. In our quest toward better understanding of C5a-C5aR interaction,2 we have recently generated the first set of atomistic model structures of inactive and meta-active C5aR in excellent agreement with the previously reported binding and signaling studies.3 Further, we have also identified a pair of “allosteric switches”4 on C5a that potentially modulate the C5aR signaling. It is noteworthy that the peptide agonist, C5a and the small molecule antagonist5 NDT demonstrate binding at the exact same site on the meta-active structure of C5aR with distinctly different binding modes.6 In summary, the inactive, agonist and antagonist bound meta-active C5aR structures provide important structural insights, previously not known at an atomistic resolution, in regard to the ligand binding sites, selectivity and activation of C5aR, which will be discussed in detail.

Durba Roy

Birla Institute of Technology & Science – Pilani, India

Title: Disulfide Bonds as Structural Scaffolds for Neurotoxic Peptides

Biography:

Durba Roy has completed her PhD In 2008 From the Indian Association for the Cultivation of Science (IACS), India And postdoctoral studies from the Pennsylvania State University and the New York University. She is an Assistant Professor at the Birla Institute of Technology and Science, Hyderabad, India. She is interested to study the role of disulfide bonds in peptides and proteins through Molecular Dynamics Simulation and how one can use computation tools towards designing engineered peptides of enhanced therapeutic potency.

Abstract:

Animal venoms are mostly composed of cysteine and disulfide-rich peptides. These peptides are neurotoxins and are highly selective in attacking a wide range of neuroreceptors and ion channels.1-2 Among these peptide toxins, conopeptides (natural toxins expressed by the carnivorous marine cone snails of the genus Conus) are used extensively in neurophysiological studies to investigate isoforms of specific neuro-receptors. These neurotoxins are often characterized by structural motifs of cysteine (Cys) and disulfide bonds, which play a vital role in dictating the overall folds in the structure of these peptide-toxins. The structure in turn is significantly responsible for the determination of toxin function and selectivity. A major challenge, which makes experimental work with the disulfide-rich venom peptides difficult, is to obtain sufficient material for structural and functional characterization. The synthesis is very difficult for these venom peptides, as they often form isoforms due to the presence of non-native disulfide-linkages. Hence, computer simulation has become an indispensable tool to study the shape, size, conformational stability, hydrodynamic behavior, folding patterns and denaturation of these peptide-toxins.3 In the present work, using microsecond order all-atom Molecular Dynamics simulation with classical force field, we are proposing to develop a general understanding of the folding pattern of such venom peptides in water in realistic time scales. How far the disulfide bond scrambling induces deviation in the structure of these neurotoxins from the native form is the fundamental answer that we are looking for. Further, we estimate quantitatively, the ratio of the different disulfide bond isoforms that would appear in equilibrium under a given reaction condition using classical MD data.

Session Introduction

Abhishek Kundu

Jadavpur University Jadavpur, India

Title: Detailed pharmacological studies of the new phytochemical PITC-2 of medicinal plant Pluchea indica (L.)Less

Biography:

Abhishek Kundu completed his PhD in biosciences at the age of 31 years from Jadavpur University, Kolkata, India and post-graduation studies in Biochemistry from M.S.Ramaiah College,Bangalore. He has published total 3 papers so far and has been serving as a senior application analyst in Agappe Diagnostics.

Abstract:

Medicinal value of plants has been significantly rewarded by Indian research background, although ancient reports based screening has been enormously persuaded. Based on the experimental evidences and statistical screening many interesting physiological properties were shown by Indian medicinal plants resulting in the isolation of clinically useful compounds. The target of a pharmacologist is to find out a significantly effective compound of better activity with negligible or no side effects. Modification of the existing drugs or by discovering a lead compound can help to achieve the goal. Active engagement in the evaluation of Indian medicinal plants used in traditional medicinal system, over the last few years have discovered that the plant Pluchea indica (L.) Less root possesses anti-inflammatory, anti-ulcer and anti-oxidant properties. The present study involves the evaluation of some pharmacological activities, i.e. antimalarial, antimicrobial and antileishmanial both in-vitro and in-vivo by employing the tissue cultured P. indica root extract,PITC-2 (isolated compound) and its derivatives. As our previous study indicates, it is safe to use in biological system as it possesses a wide range of therapeutic window.PITC2 may be a potential lead to design a new drug against MDR malaria strains. It may be concluded that PITC-2 was not only an active antibacterial agent but also is able to interfere with and restrict the action of polymerase chain reaction for rebuilding of new DNA strands.The antileishmanial activity of the crude extract, PITC-2 and its derivative proved to be rather significant and promising as well with the IC50 values of < 20µg/ml

Sezen Vatansever

Koc University, Turkey

Title: Fight against crimean congo hemorrhagic fever virus: Drug design based on repositioning known molecules

Biography:

Sezen Vatansever is PhD Candidate from Koc University, Turkey

Abstract:

Background: Crimean Congo Hemorrhagic Fever (CCHF) is the most important tick-borne viral disease of humans causing increasing numbers of fatal outbreaks or sporadic cases across a huge geographic area. CCHF virus (CCHFV), the causative agent of the illness is classified as BSL 4 pathogen and considered as a potential bio-terrorism agent in the wider world. In contrast with severity of the virus, currently no FDA-approved specific antiviral therapy is available. Ribavirin is the only therapeutic agent used for the disease, although there is no evidence of its efficacy. Our research aims to discover new drugs against CCHFV in a drug repositioning manner by using rational drug design methods. In order to achieve our aim, we proceed as following steps: Molecular Docking; Molecular Dynamics; Combined Docking and Molecular Docking Simulations and In Vito & In Vivo Tests. Molecular Docking: Molecular docking includes target identification: Viral capsid protein is chosen as the target protein. It’s active site is determined by literature-based search; Ligand sets: Small libraries which include all the FDA-approved drugs and natural compounds are downloaded from ZINC database. Additionally, the investigational antivirals are searched from published articles and the Drug Bank. Their structures are obtained from ZINC; Docking programs: In a comparative manner MVD, GOLD and Autodock Vina are used and Structure-based discovery of candidates and docking: Some of the best-scored candidates can be shared similar structures. Structure similarity search is made for those candidates by using ZINC structure-based search tool. In addition to ligand sets, resulting molecules are also docked into the protein. Molecular Dynamics (MD): It involves simulation of the capsid protein: To understand the dynamic behavior of capsid at different time scales, simulation is performed using the NAMD program. Combined Docking and MD Simulations: Steered MD (SMD) simulations is used to reveal structural changes in protein-ligand complexes which are obtained from docking study at the atomic level; Parametrization of non-standard drug-like compounds: Parametrization of drug candidates is required for SMD. In Vitro & In Vivo Tests: Viral hemorrhagic fevers continue to threat the world and CCHF is endemic in Turkey. Development of effective drugs for prevention of CCHF is now a priority for public health. Our drug repositioning approach minimizes the cost and the duration of the drug development by using computer-aided analysis with the feasibility of intelligent drug design. We completed the first step of the study. Three different compound group showed significant binding affinity to the target protein. Now, we are working on the second and third steps. We will move to labratory and clinical experiments after third step. Our methodology is unique for being the only computational study directed on CCHF. It lets us to discover potent virus-specific drugs to fight against the CCHFV. Besides, this novel approach will enable to find out specific antivirals for the treatment of emerging infectious diseases all around the world. More importantly, this work can give a solution for universal problem in virus-infected patients which are the duration of treatment and the overall survival rate of the patients.

Ashish Runthala

Birla Institute of Technology and Science Pilani, India

Title: Structural mapping of protein network aids us to unleash their evolutionary links and to design accurate drugs

Biography:

Ashish Runthala has submitted his PhD thesis and about to complete it in a month from Birla Institute of Technology and Science, Pilani. His doctoral thesis is entitled “Refinement and Improvement of Template Based Protein Modelling Algorithms”. His research interest includes Biocomputing, Structural Bioinformatics, Functional Proteomics and Biomolecular Modelling. He has published more than 25 papers and monographs in reputed journals and research volumes, and has been serving as an editorial board member of repute, also being the Reviewer of several reputed journals.

Abstract:

Functional annotation of a protein sequence and that too precisely for its every single encoded domain is challenging. As the number of protein sequences is rapidly growing, the overwhelming count of proteins can only be annotated computationally, although a high accuracy is always expected. Decade is gone when the protein sequence could be annotated through the statistical scoring of its similarity with the existing database of functionally understood protein sequences. A protein structure is naturally too robust over its primary sequence information. To decode the functional attributes of a protein, the task of modelling, assessing and comparing a best predicted protein model with the functionally understood protein or domain conformations becomes a promising exercise. Majority of these protein structure prediction algorithms fail to construct the accurate near-native model with the correct structural topology of each of the encoded domain and with an acceptable mutual orientation of these domains in the overall protein model. The improved protein modelling algorithm is hereby first presented to bridge the sequence-structure gap and the challenge of predicting the functional detail of a protein sequence is further resolved. Smooth mapping of the evolutionary link and biochemical network of protein sequences in a cell is thereby emphasized to develop the best set of composite drugs for effectively curing even the currently unresolved deadly diseases.

Session Introduction

Aparna Rai

Indian Institute of Technology-Indore , India

Title: Randomness and preserved patterns in cancer network

Biography:

Aparna Rai completed her Master of Technology in Biotechnology from Lovely Professional University, Jalandhar, India. She is currently a Research Scholar under Dr. Sarika Jalan, Complex Systems Lab, Indian Institute of Technology Indore, Indore, India. Her main aim of research is to understand the complexity of diseases using combined framework of network theory and various mathematical and statistical tools such as Random Matrix Theory.

Abstract:

Breast cancer has been reported to account for the maximum cases among all female cancers till date. Complexity as well as variations at every stage of the cancer renders designing drug targets very difficult. The ample availability of data in functional genomic and proteomic information and the development of high-throughput data-collection techniques have resulted from basic gene-based traditional molecular biology to a systems approach of network biology. In this approach, biological processes are considered as complex networks of interactions between numerous components of the cell rather than as independent interactions involving only a few molecules. We analyze the breast cancer network and its normal counterpart at the proteomic level. The spectral analysis reflects that robustness of the overall system is decreased in the disease but the interactions of the important proteins involved in promoting the disease are preserved and might be one of the reasons behind making those pathways involved with the important proteins highly resistant to various treatments. Detection of important proteins involved in breast cancer using random matrix theory platform provides a time efficient and cost effective approach for those diseases, which lack in-depth information about important genes. The analysis provides a benchmark for designing drugs, which can target a sub graph instead of individual proteins.