Scientific Program

Conference Series Ltd invites all the participants across the globe to attend 2nd International Conference on Genetic and Protein Engineering Atlanta, Georgia, USA.

Day 1 :

Keynote Forum

Ram Samudrala

State University of New York, USA

Keynote: Interactomics: computational analysis of novel drug opportunities

Time : 10:00-10:40

Conference Series Protein Engineering 2016 International Conference Keynote Speaker Ram Samudrala photo
Biography:

Ram Samudrala is Professor and Chief, Division of Bioinformatics, State University of New York, Buffalo researching multi scale modeling of atomic, molecular, cellular and physiological systems with an emphasis on protein and proteome structure, function, interaction, design and evolution. His work has led to more than 115 publications in journals such as Science, Nature, PLoS Biology, the Proceedings of the National Academy of Sciences and the Journal of the American Medical Association. He has joined the University of Washington Faculty in 2001 (where he remains as an Affiliate Professor) after completing his Doctoral research with John Moult at the Center for Advanced Research in Biotechnology in 1997 and his Postdoctoral research with Michael Levitt (2013 Nobel in Chemistry) at Stanford University in 2000, which resulted in him making some of the best predictions at the first three community-wide assessment of protein structure prediction (CASP) experiments.

Abstract:

We have developed a Computational Analysis of Novel Drug Opportunities (CANDO) platform funded by a 2010 NIH Director’s Pioneer Award (http://protinfo.org/cando) that analyses compound-proteome interaction signatures to determine drug behaviour, in contrast to traditional single target approaches. The platform uses similarity of interaction signatures across all proteins as indicative of similar functional behaviour and nonsimilar signatures (or regions of signatures) as indicative of off- and anti-target (side) effects, in effect inferring homology of compound/drug behaviour at a proteomic level. We have created a matrix of predicted interactions between 3,733 human ingestible compounds (including FDA approved drugs and supplements) × 48,278 proteins using our hierarchical chem and bio-informatic fragment-based docking with dynamics protocol (from over one billion predicted interactions total).  We applied our compound-proteome signature comparison and ranking approach to 2030 indications with one approved compound and yielded benchmarking accuracies of 12-25% for 1439 indications with more than approved compound. We are prospectively validating "high value" predictions in vitro, in vivo, and by clinical studies for more than forty indications, including dental caries, dengue, tuberculosis, ovarian cancer, cholangiocarinomas, among many others. 58/163 (36%) predictions from twelve studies covering ten indications show comparable or better activity to existing therapies, or micromolar inhibition at the cellular level, and serve as novel repurposeable therapies.  Our approach is applicable to any compound beyond those approved by the FDA, and also include can readily consider mutations in protein structures to enable personalisation based on genotype, foreshadowing a new era of faster, safer, better and cheaper drug discovery.  Our approach also has other application in areas such as synthetic biology and nanobiotechnology.  In this presentation, we will describe the latest developments in the CANDO platform, with a focus on characterisation of host-microbiome-drug interactions

Conference Series Protein Engineering 2016 International Conference Keynote Speaker Dmitry G. Vassylyev photo
Biography:

Dmitry G. Vassylyev has completed his PhD at the age of 30 years from Institute of Molecular Biology Acad. Sci. USSR (Mosow) and postdoctoral studies from Bioengineering Research Institute (Osaka, Japan). From 2005, he is the Full Professor at the University of Alabama at Birmingham. He is an expert in protein crystallography and has published 84 papers in the top level scientific journals.

Abstract:

Protein purification is an essential, primary step in numerous biological studies, including a rapidly emerging proteomics field, its structural counterpart and drug screening. Moreover, purification with high yield, purity and activity (HHH-purification) is compulsory for high-resolution structural analysis and industrial protein production. Apparently, a universal, one-step high-throughput approach for HHH-purification is a key, yet unachievable, factor of success for all these crucial studies/applications.  We designed and implemented an original chromatographic technology based on the physiological, ultra-high affinity (Kd~10-14-10-17 M) small (~10/16 kDa) protein/protein complex, which allows for a one-step HHH-purification of the traditionally challenging (eukaryotic, membrane, multi-subunit, DNA/RNA-binding, toxic) proteins. The developed system is practically indefinitely reusable, suitable for industrial-scale manufacturing, has high capacity (up to 20mg tagged protein per ml beads) and efficiently operates under nearly identical (target-independent) basic conditions. Altogether, it provides major advantages over the existing commercial analogs and may form a solid high-throughput platform for both, purification and associated “affinity” techniques (pull-down, kinetic activity/binding assays, etc.) of protein characterization.

  • Track 1 : Protein Engineering |Track 2 : Applications of Genetic and Protein Engineering | Track 3 : Protein Purification
Location: Chittahoochee B
Speaker

Chair

Peter Luan

Genentech Inc., USA

Speaker

Co-Chair

Xiao-Qing Qiu

West China Hospital-Sichuan University

Session Introduction

Peter Luan

Genentech Inc., USA

Title: Doing more with less: automated workflows for high throughput microscale antibody purification

Time : 11:40-12:10

Speaker
Biography:

Mr. Peng Luan has worked on protein therapeutics for 20 years in the biotech/pharmaceutical industry. He holds a Master of Science degree from University of Nebraska-Lincoln and is currently a Sr. Scientific Researcher at Genentech, Inc.  His recent work has been involvedin developing high throughput purifications that enable large antibody discovery campaigns. He is a co-inventor on five issued U.S. patents and had several journal publications on therapeutic protein engineering and productions.

Abstract:

Due to the revolutionary impact of monoclonal antibodies in the field of therapeutics and diagnostics, more pharmaceutical companies are expanding their antibody discovery efforts. In early research, various types of IgGs from multiple species are generated through hybridoma, phage library and other antibody discovery technologies. In large campaigns, thousands of antibodies are often expressed in micro-scale (~ 1 mL) by high throughput (HTP) hybridoma culture or transient expression in 96 well culture blocks. Availability of purified antibodies significantly improves the reliability of “hit identification” from HTP screening assays. To improve efficiency and consistency, we have developed automated HTP workflows using two liquid handling platforms, resulting purification capacity of ~2000 antibodies in a single day with just one operator. In addition to supporting antibody discovery or engineering campaigns with thousands of purified proteins, these HTP work flows have also enabled rapid in-parallel testing of purification conditions using design of experiment (DOE) principles. For instance, purification of certain antibody formats (such as Fabs) and some murine or rat antibodies (such as Rat IgG2a) necessitates pH and/or salt adjustment with commonly used resins (Protein A or G), making the process impractical for HTP implementation. Using our HTP approaches we have identified a commercially available,engineered protein G resinthat can capture all rat IgGs under physiological conditions and have optimized elution conditions to maximize antibody recovery.

Speaker
Biography:

Dr. Broersen completed her doctorate in the field of protein aggregation at Wageningen University in The Netherlands in 2005. After her postdoctoral study at the MRC-LMB in the UK, she joined the Free University of Brussels (VUB)/Flanders Institute for Biotechnology (VIB) in 2007. Here she headed a research team that studied the molecular mechanism of Alzheimer’s disease. This led to the discovery of molecular pathways of a number of risk factors that affect Alzheimer’s disease pathobiology. Subsequently, she joined the Nanobiophysics Group at the University of Twente/MIRA Institute in The Netherlands as an assistant professor investigating further the impact of protein structures on human health with her team. 

Abstract:

One of the most prominent hallmarks detected in the brains of patients suffering from Alzheimer’s disease is the deposition of amyloidogenic plaques. These plaques are largely composed of the amyloid-beta peptide. It has been demonstrated that, even though these plaques comprise an important and recurring feature for disease, that precursor forms of these plaques, called ‘oligomers’ or ‘protofibrils’ more potently affect neuronal functioning. Accumulation and subsequent assembly of amyloid-beta peptide into aggregated forms has been reported to be partly brought about by an impaired clearance of the amyloid-beta peptide. Lowering the amyloid-beta peptide burden by increasing clearance provides a promising avenue for treatment of Alzheimer’s disease.

A number of proteases have been reported to cleave amyloid-beta peptide in vivo or in vitro. Drug compounds are under development that can modulate enzymatic activity to selectively enhance amyloid-beta peptide degradation. In view of the development of proteolytic-based therapies, more insight into the amyloid-beta peptide-degrading capacity of enzymes is required. For example, the effect of amyloid-beta proteolytic enzymes on various misfolded forms of the peptide has been little documented in the literature. Also the effect of in vivo occurring combinations of enzymes has not been explored. Moreover, the properties of enzyme-induced fragments from Aβ are currently unknown. To extend our understanding of the potential therapeutic utility of amyloid-beta peptide proteolytic enzymes, we investigated enzyme-mediated cleavage of amyloid-beta peptide in vitro using biophysical and biochemical assays and we identified new cleavage sites, cooperative activity of enzymes and characterized the potential aggregation behavior of resulting fragments.

Niv Papo

Ben-Gurion University of the Negev, Israel

Title: Rational and combinatorial engineering of protease inhibitors for cancer imaging and therapy

Time : 12:40-13:10

Speaker
Biography:

As a molecular biologist focusing on protein engineering and cancer imaging and therapy, Dr. Papo joined the BGU faculty in 2011, and his research focuses on the development of new nono- and multi-specific proteins and protein-small molecule conjugates that promise to aid in both the diagnosis and treatment of cancer. Dr. Papo’s areas of expertise include protein engineering, angiogenesis, metastasis, cancer biology, targeted cancer therapy, in vivo imaging, directed evolution, ligand-receptor interactions, molecular recognition, protein sequence-structure-function relationships, and synthetic biology. More generally, Dr. Papo and his research team are developing methods that allow us to design nono- and multi-functional proteins with optimized and targeted pharmaceutical properties, such as the protein’s distribution in the body and how long it remains, resulting in enhanced alternatives to antibodies that will benefit both cancer therapy and diagnostics. 

Abstract:

Mesotrypsin, an enzyme that contributes to progression and metastasis ofmany cancers,constitutes a compelling therapeutic target. However, with its unique capability for cleavage and inactivation of proteinaceous inhibitors, mesotrypsin presents a formidable challenge to the development of biologic inhibitors.Our study identifies a promising mesotrypsin inhibitor – a triple mutant of the human amyloid precursor protein Kunitz protease inhibitor domain (APPI) with superior affinity, specificity, and proteolytic stability – as a starting point for the development of anticancer protein therapeutics. We demonstrate that the mutant acts as a functional inhibitor of mesotrypsin-dependent prostate cancer cellular invasiveness. Additionally, the crystal structure of the mutant/mesotrypsin complex provides new insights into the structural and mechanistic basis for the mutant's improved binding and proteolytic resistance. Finally, the study establishes proof-of-principle for a novel library screening approach that is widely applicable for simultaneously evolving proteolytic stability and a desired functionality for diverse protein scaffolds.

Speaker
Biography:

Prof Dr Frédéric CADET (PEACCEL, Paris, France): Vice President Research & Development of the company Peaccel (Protein Engineering ACCELerator: http://www.peaccel.com). Ph.D (specialization in: Protein Engineering, Data mining, Biosimulation). From 2004 to 2008, as an “Executive School, University & Research Commissioner”, he managed a budget of 1.3 billion Euros and was responsible for 32,000 employees. Former Chairman of the ERA Nets (European Research Area Networks) NetBIOME. He has developed pioneering research activities in bioinformatics. Author of over 70 publications and referee for 17 international scientific journals. Organizing Committee Member for « 2nd International Conference on "Genetic and Protein Engineering”, November 14-16, 2016 Atlanta, USA.

Abstract:

The knowledge of organisms and their metabolic pathways allowed to construct biological systems for the production of chemicals and pharmaceuticals such as antibiotics and biofuels. Synthetic biology expands the number of these biological systems by the assembly of artificial metabolic pathways, called synthetic pathways, not present in natural organisms. Synthetic pathways could be integrated in modified micro-organisms or in biocatalyst systems. A biocatalyst system is an in vitro assembly composed only of purified enzymes and metabolites that are useful for the production of a desired metabolic compound through a biochemical reaction network. This in vitro assembly, as compared to cellular system, has several advantages, such as the production of only desired metabolites and a great engineering flexibility. We explored an in silico approach to identify and analyse new biocatalyst systems for the production of target metabolic compounds. This approach proceeds in several steps. The first step is the enumeration of several biocatalyst systems that could synthesize a target product from a desired starting substrate. Next, a selection based on several criteria is applied to choose a biocatalyst system among the group of biocatalyst systems identified in the enumeration step. The last step is the modelling of the selected biocatalyst system to evaluate the production rate and the yield of the target product. This communication explains in more detail the modus operandi for the different steps of our in silico approach.

Du Qing

Fresh-skyright International Science and Technology Co. Ltd., China

Title: IDI has the key function during the biosynthesis of terpenoids compound

Time : 14:40-15:10

Speaker
Biography:

Duqing has completed his PhD at the year 2015 in the major of pharmacognosy from the institute of medicinal plant development ,Chinese academy of Medical Sciences(CAMS) and Peking Union Medical College(PUMC) and got the doctor degree in 2016.Duqing begin the postdoctoral studies in the institute of genetics and developmental biology,Beijing,China from the July of 2015 to August of 2016.I am the member of American Society of Plant Biologists and Chinese Society for Cell Biology.Moreover,I am a pharmacist and the member of Chinese Pharmacist Association. We have published more than 5 papers in the BMC and Chinese famous journals as the research group. 

Abstract:

Terpeniod compound can be classified into monoterpenes((C5H8)2),sesquiterpenes((C5H8)3),

diterpenoids((C5H8)4),triterpenoids((C5H8)6) and polyterpenes((C5H8)2,n>6) according to the numbers of Isoprene or isopentane((C5H8)n) and the derivative of having the oxygen and different saturation degree from the structure.The biosynthesis of different terpeniod compound can be produced depends on cross-talk between the MEP pathway and the mevalonate (MVA) pathway. IDI(Isopentenyl diphosphate isomerase)is the common and key enzyme related to the biosynthesis of terpeniod and gibberellin compounds.It is well known that the IDI gene families exit in the diverse species of the earth and have been carried out the research works in the plants of  Arabidopsis annua L./Artemisia apiacea、the fungus of Ganoderma lucidum etc.Why do I think the essential and important of IDI gene families regarding the biosynthesis of terpenoids compound?Because IDI gene families locate in the upstream of the pathway.The function and change of it can bring the influences or actions to the whole course of metabolism pathway and downstream products.We can not ignore the essence of research courses or dynamics on the direction of research projects.The quantities of IDI gene families are found it is not same or diverse because of the assay and characteristics involved in the species.Moreover,IDI gene families has the certain function during the course of reciprocal transformation between the gene families of IPP and DMAPP.I will give the review in the way of presentation from the aspects of exist formation,identification,cloning sequences,tissue-specific expression,protein structures and functions and applications of the different creatures so as to acquire the supports and good advice coming from the experts who are interested and has the famous experience about the research projects.

Xiao-Qing Qiu

West China Hospital-Sichuan University, China

Title: Pheromonicin, a fusion-protein against drug-resistant pathogens

Time : 15:10-15:40

Speaker
Biography:

Xiao-Qing Qiu has completed his PhD in 1991 from Emory University and postdoctoral studies from Albert Einstein College of Medicine at NYC in 1996. He is the director of Lab. of Biomembrane & Membrane Proteins and full Professor of Sichuan University. He has published more than 10 papers in reputed journals. Mainly engaged in developing a novel fusion-peptide antibiotic, pheromonicin, against drug-resistant pathogens. 56 related patents have been approved by China, US, and other countries patent offices.    

Abstract:

A new strategy in the development of antibiotics against the threat of antibiotic resistance is to simply adopt defense strategies of bacteria themselves. Bacteriocins, antimicrobial peptides produced by bacteria, are an essential entity of such strategies. Colicins are channel-forming bacteriocins produced by Escherichia coli. They are bactericidal to other E. coli strains by forming a voltage-activated channel in the cell membrane.

Here we constructed a peptide consisting of a 28-residue antibody mimetic fused to the channel-forming domain of colicin Ia and named it pheromonicin. By altering native targeting of colicins, antibody mimetic targets fused colicin to form a lethal channel in the cell membrane to lead the leak/death of targeted pathogens.

Pheromonicins have nano-molar efficacy against thousand clinical isolates of antibiotic-resistant Gram-positive and -negative pathogens while they left enteric probiotic bacteria, lactococcus, lactobacillus and Bifidobacterium unaffected at the dosages that effectively killed pathogens. In thousand rodents, poultries, ungulates and non-human primate models, pheromonicin-treated animals survived administration of MRSA, or VRE, or MDR P. aerugenosa, or MDR M.tuberculosis at doses that were lethal to controls.

With the inheritance of colicin’s native advantages, nano-molar efficacy, the ability to act in the host circulation, no toxicity and easy genetically engineered, pheromonicin application cleared fatal bacterial infections in vivo that did not respond to currently employed antibiotics (vancomycin, amoxicillin, oxacillin, carbapenem etc). Pheromonicin may be of value as a novel antibiotic against MDR pathogens with targeted bactericidal and cytokine modulating activities.

Speaker
Biography:

D.L.Savithramma has completed her PhD at the age of 35 years from University of Agricultural Sciences, Bangalore, India and postdoctoral studies as a Biotechnology National Associate from Indian Institute Science, Bangalore, India. She is a Professor of Genetics and Plant Breeding at University of Agricultural Sciences, Bangalore, India, one of the premier Agricultural University in India. She has published more than 70 papers in reputed journals and has released seven varieties in Vegetable cowpea, seed cowpea, Peanut and Chrysanthemum

Abstract:

Plant root is one of the major organs for water and nutrient uptake from soil. Root development and amount of water absorption from the soil are closely related. Under drought condition the success of crop plants often depend on growth of roots. In the present study gravimetric experiment was conducted to evaluate the yield potential of released and pre released groundnut genotypes.Root growth parameters such as root length, shoot length, shoot weight, leaf length, root volume and dry root weight were recorded in five genotypes viz., KCG-2, TMV-2, GKVK-5, GKVK-3 and GKVK-13 under controlled and water stress conditions in pot experiment at University of Agricultural Sciences, Bangalore, India. Stress was imposed for 20 days during flowering stage by balancing the amount of water applied to make it 50% stress. Analysis of variance revealed highly significant differences for the traits observed indicating the existence of variability in the material selected. In controlled condition all the root traits exhibited higher mean values over stress condition in the genotypes studied except in GKVK-5 for root dry weight. In stress treatment GKVK-5, GKVK-3 and GKVK-13 genotypes exhibited higher mean values for root volume, root dry weightand root length. Genotypes GKVK-5, TMV-2 and KCG-2 recorded higher mean for shoot weight and leaf length. Among all genotypes GKVK-5 was identified as high yielding with 2.8 to 3.0 t/ ha, with low to moderate Δ13C (17.53) and high δ18O (31.24) and low specific leaf area(107.76cm2/g)and was found to have higher Water Use Efficiency or to be drought tolerant genotype indicating effective partitioning of the accumulated biomass towards root and shoot, while diverting relatively lesser towards shoot biomass. Hence, breeding for root development proved to be effective in increasing crop Water Use Efficiency and drought tolerance.