Scientific Program

Conference Series Ltd invites all the participants across the globe to attend 4th International Conference on Integrative Biology Berlin, Germany.

Day 1 :

Keynote Forum

Hans Lehrach

Max Planck Institute for Molecular Genetics, Germany

Keynote: Virtualized drug development for (truly) personalized drug therapy

Time : 09:45-10:15

OMICS International Integrative Biology 2016 International Conference Keynote Speaker Hans Lehrach photo
Biography:

Hans Lehrach has studied Chemistry in Vienna and obtained his PhD at the Max Planck Institute for Experimental Medicine and the MPI for Biophysical Chemistry in 1974. He then moved on to Harvard University, Boston (1974-1978) and then became Group Leader at EMBL, Heidelberg (1978-1987). He has then joined the Imperial Cancer Research Fund, London (1987-1994) as a Head of the Genome Analysis Department. In 1994, he has returned to Germany to become Director at the MPI for Molecular Genetics. He has founded several biotechnology companies such as Sequana Therapeutics, GPC Biotech, Scienion, [email protected], PSF Biotech and Atlas Biolabs. He is the Founder of the Berlin-based company Alacris Theranostics GmbH, specializing in the development of new approaches for personalized medicine for cancer patient diagnosis, treatment and drug stratification. In 2010, he has founded the non-for-profit research institute Dahlem Centre for Genome Research and Medical Systems Biology.

Abstract:

Every patient is different. In particular, every tumor is different. Even subgroups of tumor cells can react differently to specific therapies, due to the heterogeneity of many tumors. Drug therapies therefore typically only help a fraction of patients; many patients do not respond with some suffering sometimes severe side effects of ineffective treatments. The ability to identify effects and possible side effects of different drugs on individual patients will, in our view, require highly detailed molecular analyses of every individual patient and his/her individual disease; data that is integral to generating individualized computer models, which can then be used to test the effects of drugs (or other therapies) on the individual. This will, on one hand, provide a basis for a truly personalized selection of therapies optimal for the individual patient, first in cancer patients but increasingly also in other areas of medicine and prevention. It will, however, also open the way to an increasing virtualization of the drug development process, by e.g., virtual clinical trials of drug candidates carried out throughout the development process.

OMICS International Integrative Biology 2016 International Conference Keynote Speaker Armando Del Rio Hernandez photo
Biography:

Armando Del Rio Hernandez obtained his PhD in Chemistry from the Computense University in Madrid. Following this, he completed a period of Postdoctoral training in the US. He worked at Columbia University of New York as a Research Fellow first, and as a Research Associate, later. He currently leads the Cellular and Molecular Biomechanics group in the Department of Bioengineering at Imperial College London. He is a European Research Council Fellow and Editorial Board Member of several journals.

Abstract:

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers with a 5-year survival rate of less than 4%. This rate has remained unchanged for the last 40 years despite advances in conventional therapies targeting cancer cells. PDAC tumours are characterised by remarkable matrix stiffness, and a strong desmoplastic reaction that is mediated by the main cellular component in the tumour microenvironment – pancreatic stellate cells (PSCs). Activated PSCs cross-talk with cancer cells to promote tumour growth, metastasis and chemoresistance, but the molecular mechanism that keeps PSCs persistently activated remains unknown. Our studies implicate retinoic acid receptor as a regulator of traction forces and mechanosensing in PSCs, and this regulation influences the capacity of PSCs to migrate, to remodel the extracellular matrix (ECM), and to promote pancreatic cancer cell invasion.

Keynote Forum

Reinhard Luhrmann

Max Planck Institute for Biophysical Chemistry, Germany

Keynote: Structural basis of pre-mRNA splicing

Time : 11:00- 11:30

OMICS International Integrative Biology 2016 International Conference Keynote Speaker Reinhard Luhrmann photo
Biography:

Reinhard Luhrmann studied doctorate with Prof. Gassen from University of Münster (1973-1975), postdoctoral fellow with Prof. H. G. Wittmann at the MPI for Molecular Genetics, Berlin (1976-1980), Leader of a Max Planck junior research group, habilitation in Biochemistry and Molecular Biology Free University Berlin (1982), Professor for Physiological Chemistry and Molecular Biology Univ. Marburg (1988-1999), Director and Scientific Member at the MPI for Biophysical Chemistry, honorary professor at the Universities of Göttingen and Marburg. Numerous scientific prizes, among them the Max Planck Research Prize (1990), the Gottfried Wilhelm Leibniz Prize (1996), the Feldberg Prize (2002), and the Ernst Jung Prize for Medicine (2003).

Abstract:

The spliceosome catalyses the removal of the intron from nuclear pre-mRNAs and assembles initially into a pre-catalytic ensemble, termed complex B, which contains the snRNPs U1, U2 and the U4/U6.U5 tri-snRNP and numerous non-snRNP proteins. For catalytic activation the spliceosome undergoes a major structural rearrangement, mediated by the Brr2 RNA helicase, yielding the activated spliceosome (Bact complex). The final catalytic activation of the spliceosome requires an additional restructuring step by the RNA helicase Prp2. Using cryo electron microscopy we have investigated the 3D structure of the human U4/U6. U5 tri-snRNP complex and the yeast activated spliceosome. Our tri-snRNP model reveals how the spatial organization of Brr2 RNA helicase prevents premature U4/U6 RNA unwinding in isolated human tri-snRNPs and how the Sad1 protein likely tethers Brr2 to its pre-activation position. The structure of the yeast Bact complex reveals how the first step reactants (i.e., the 5' splice site and the branch site adenosine) are sequestered by protein prior to catalysis and provide insights into the molecular remodeling events that must be facilitated by Prp2 in order to generate a catalytically active spliceosome. In addition, comparison of the Bact spatial organization with the cryo-EM structures of the tri-snRNP reveal how many spliceosomal components are rearranged during activation of the spliceosome.

Keynote Forum

Mark Bronstrup

Helmholtz Centre for Infection Research, Germany

Keynote: Chemical biology directed to anti-infective drug discovery

Time : 11:30- 12:00

OMICS International Integrative Biology 2016 International Conference Keynote Speaker Mark Bronstrup photo
Biography:

Mark Bronstrup has studied chemistry and obtained his PhD from the TU Berlin in 1999. He has joined Aventis in 2000 and spent a research sabbatical with S. P. Gygi at Harvard Medical School in 2003. Between 2005 and 2010, he was leading the Natural Products Science section at Sanofi Aventis in Frankfurt. Between 2010 and 2013, he was managing sections dealing with biomarkers, bioimaging & biological assays. Since December 2013, he has been Head of the Chemical Biology Department at the Helmholtz Centre for Infection Research in Braunschweig and W3 Professor at the University of Hannover. His research is focused on the discovery, the characterization and the optimization of novel anti-infective drugs.

Abstract:

Our efforts to generate novel antibacterial and antiviral lead substances through chemical biology methods will be highlighted through two projects. Infections caused by pathogenic bacteria represent a major health threat that is expected to rise further in the future. The need for novel antibiotics is currently not met by R&D efforts, in particular in the area of infections caused by Gram-negative bacteria. A main scientific hurdle is the lack of understanding how to assure a sufficient translocation of bioactive molecules across the Gram-negative cell wall. In the talk, our efforts to induce an active transport of small molecules into Gram negative bacteria and methods to quantify such uptake will be presented. We report a series of theranostics agents based on DOTAM derivatives comprising siderophores that actively target bacteria, inhibit bacterial growth and demonstrate efficacy to visualize bacterial infections in mice by optical imaging in vivo. In addition, two orthogonal approaches to quantify the intracellular accumulation of such conjugates will be presented. In the second part of the talk, two antiviral natural products with broad-spectrum action against multiple human pathogenic viruses will be presented. Broad spectrum antiviral agents have the potential to improve health-care of infected individuals including patients infected with emerging viruses against which no directly acting antiviral drug is yet available, patients co-infected with two or more viruses and patients infected with viruses that have developed resistance to standard antiviral treatment. Both lead compounds interfere with extra and intracellular lipid metabolism pathways utilized by different viruses.

  • Cell Biology | Developmental Biology | Stem Cell Biology | Tissue Biology
Location: Experience II

Chair

Anja Nohe

University of Delaware, USA

Co-Chair

Jamila Chakir

Laval University, Canada

Biography:

Eva Collakova has obtained her PhD in 2003 from Michigan State University, where she has also completed her Postdoctoral studies. In 2009, she became an Assistant Professor at Virginia Tech, USA. She is currently an Associate Professor at the Department of Plant Pathology, Physiology and Weed Science at Virginia Tech. She has published over 20 manuscripts in peer-reviewed journals, including top plant research-related journals, e.g., Plant Cell, Plant Physiology and Plant Journal and has served as a Reviewer of over 25 manuscripts for international journals and as a Panelist and an ad-hoc Reviewer for Federal Grant Agencies in the US.

Abstract:

Seed development and metabolism in Arabidopsis are regulated by leafy cotyledon1 (LEC1), Abscisic acid-insensitive3 (ABI3), Fusca3 (FUS3) and LEC2. These transcription factors are part of the core LAFL (LEC1, ABI3, FUS3, and LEC2) regulatory network central to seed development. The action of the LAFL transcription factors is inhibited in germinating seedlings by VAL1 and 2 to suppress the embryonic program during the transition from the embryonic to vegetative state. However, the VALs are also expressed in maturing seed, which appears controversial, considering their role in suppressing the embryonic program. Two VAL1 splice variants were identified through RNA sequencing in developing Arabidopsis embryos: A full-length form containing four domains known to be involved in transcriptional and/or epigenetic regulation and a truncated form lacking the plant-homeodomain-like domain associated with epigenetic repression. Reverse genetics revealed limited influence of the VAL1 absence on seed and embryo metabolomes. However, 3,293 and 2,194 transcripts were up and down-regulated, respectively, in developing val1 mutant embryos relative to the wild type, suggesting that VAL1 is a global regulator of gene expression in developing embryos. Interestingly, none of the transcripts encoding the core LAFL network transcription factors were affected in val1 embryos. Instead, activation of VAL1 by FUS3 appears to result in repression of a subset of seed maturation genes downstream of core LAFL regulators. Transcripts that were not LAFL targets were also de-repressed in developing val1 embryos. Taken together, VAL1 appears to repress its targets through LAFL-dependent and independent mechanisms through epigenetic and/or transcriptional regulation.

Hilal Turkoglu Sasmazel

Atilim University, Turkey

Title: Hybrid PCL/chitosan scaffolds with micro and macro porosity

Time : 12:20-12:40

Biography:

Hilal Turkoglu Sasmazel is working in Metallurgical and Materials Engineering Department at Atilim University, Ankara, Turkey since 2007. Her areas of interest are biomaterials, nanomaterials, tissue engineering, polymeric and composite materials, materials surface modifications and characterizations. She was honored with TUBA-L’Oreal-UNESCO Young Women in Science Award in Materials Engineering in 2009. She has published 21 SCI research articles and has 31 conference presentations in the last 15 years. She is the Director of Polymer Composite Materials, Biocompatibility of Biomaterials and Antibacterial Property Testing Laboratories at Atilim University. She is an MC Member and representative of Turkey in EU-COST MP1101, MP1206 and FP1405 actions.

Abstract:

In this study, hybrid PCL/chitosan polymeric scaffolds have been developed by combining electrospinning, solvent casting and freeze drying techniques. The aim was to obtain a hybrid structure with micro and macro porosity. The fabrication of the scaffolds has been designed in three steps. In the first step, PCL solution, prepared by dissolving 15 weight% PCL in chloroform/methanol solvent (v/v, 75/25), was electrospun in order to obtain fibrous mats with microporous structure. In the second step, chitosan solution, dissolved in acetic acid, was cast into a Petri dish and the prepared PCL fibrous mat was immersed into the solution to combine PCL with chitosan. For a better integration of the chitosan solution to the pores of the PCL fibrous network, pressure was applied on top of the PCL mat. Finally, the samples were freeze-dried with two different pre-drying step, refrigerating and vacuum incubating, to obtain macropores, accompanying the micropores of the fibrous structure. These prepared scaffolds were found to have a structure similar to the natural extracellular matrix (ECM) with an average contact angle of 68.93±2.18o. The optimization of the fabrication parameters was carried out with naked eye observations, SEM analysis and mechanical testing. It was found that the scaffold, freeze dried for 24 hours, showed the highest Young’s modulus and yield strength values. Additionally, thickness and water contact angle (CA) measurements, Fourier Transform Infrared Spectroscopy (FTIR) and PBS absorption/shrinkage studies were carried out to define physical and chemical properties of the developed scaffolds. Finally, the biocompatibility of the scaffolds was tested in vitro with MRC5 fibroblast cells regarding cell attachment and growth and the developed scaffold was found to have better biocompatibility than commercial tissue culture polystyrene.

Biography:

Eva E Qwarnstrom is a Professor of Cell Biology at the University of Sheffield and holds an honorary affiliated Associate Professorship at the University of Washington, Seattle. She has obtained her PhD degree from the University of Lund, Sweden, following a Fellowship at the National Institute of Health, Bethesda, USA. She is a Member of Editorial Boards and scientific advisory committees.

Abstract:

Members of the toll-like and IL-1 receptor family (TIR) are central regulators of immune and inflammatory responses. Signal activation is induced through ligand binding and controlled by system specific co-receptors. The IL-1RI co-receptor TILRR is a splice variant of FREM1. TILRR association with the signaling receptor magnifies IL-1 induced activation of the canonical and non-canonical NF-B network by enhancing signal amplification at the level of the receptor complex and potentiates recruitment of the MyD88 adapter and PI3 kinase. TILRR controlled MyD88 dependent activation of the canonical pathway is regulated in a Ras-dependent manner, reflected in alterations in cytoskeletal structure and cell adhesion. The changes induced provide a process for rapid control of NF-B, involving sequestration and release of cytoskeletal bound IBα through a mechanism controlled by TILRR signal amplification. In silico simulations using agent based modeling of the NFB network predict cytoskeletal control of inhibitor levels to provide a mechanism for signal calibration and to enable activation-sensitive regulation of NFB induced inflammatory responses. Our studies have identified two functional sites within the TILRR core protein, which selectively control inflammatory and anti-apoptotic responses. The mechanisms underlying distinct network amplification and the relevance of pathway-specific regulation of canonical and non-canonical NFB activation will be discussed.

Anja Nohe

University of Delaware, USA

Title: New treatments for articular cartilage formation and repair

Time : 13:50-14:10

Biography:

Anja Nohe is an Associate Professor in the Department of Biological Sciences at the University of Delaware, USA. She has received her PhD in Chemistry in 2000. After a Postdoctoral fellow at the University of Western Ontario in Canada, she accepted a first faculty position at the University of Maine in Chemical and Biological Engineering. In 2008, she relocated to the University of Delaware, USA. She is a Member of several Editorial Boards. She uses novel imaging approaches such as AFM and the family of Image Correlation Spectroscopy to define cellular processes during stem cell differentiation and skeletal formation. Moreover, utilizing novel techniques and tools such as real time imaging and nanoparticles, she focuses on protein dynamics in cells as well as on protein distribution in mice.

Abstract:

Osteoarthritis (OA) is characterized by the progressive degradation of articular cartilage. There are no treatments today that can stop or reverse the loss of cartilage degradation. A desperate need for treatment options are on the rise as does the OA cases on an annual basis. Growth factors like Bone Morphogenetic Proteins (BMPs) are known to be present throughout the chondrocytic lineage and influence their secretion of extra cellular matrix (ECM) that is essential for the formation of articular cartilage. However, BMPs usage as a therapeutic has many drawbacks as they are known to initiate chondrocyte hypertrophy and cartilage degradation. In order to develop a more specific treatment we designed a peptide CK2.1. Using state of the art imaging techniques and system biology approaches we designed a peptide that activates a very specific BMP2 signaling pathway without the induction of chondrocyte hypertrophy. Injection into the tail vein of mice reveals increased articular cartilage formation. Additionally, markers for cartilage formation such as collagen type IX are up-regulated. This is in sharp contrast to BMP2 injection. BMP2 injection up-regulated collagen type X and MMP13 markers for hypertrophy. Second harmonic imaging of the cartilage shows a more improved structure of the cartilage. These data make CK2.1 a peptide that can restore cartilage without induction of hypertrophy and a useful therapeutic for OA treatment.

Talila Volk

Weizmann Institute of Science, Israel

Title: The mechanobiology of muscle nuclei: Mechanism and functional significance

Time : 14:10-14:30

Biography:

Talila Volk gained a BSc in Biology at Tel Aviv University. She continued her scientific training at the Weizmann Institute of Science, Rehovot, where she completed her MSc and PhD degrees in the laboratory of Benjamin Geiger. She then moved to the laboratory of John Fessler at UCLA for her postdoctoral studies. In 1990, Talila returned to Israel and, during the years that followed, she became a faculty member in the Department of Molecular Genetics at the Weizmann Institute, where she currently works.

Abstract:

Nuclear shape and morphology is essential to maintain the epigenetic state of the genome and is robust in differentiated cells. In contrast to nuclei in non motile tissues, nuclei in differentiated skeletal and cardiac muscles are facing iterated and altered cytoplasmic mechanical forces, produced by muscle contraction/relaxation waves. Recent findings from several labs (including ours), uncovered a muscle-specific network of nuclear associated cytoskeletal proteins, which is essential to protect muscle nuclei from the variable cytoplasmic strain induced by muscle contraction/relaxation and consequently is essential for the maintenance of myonuclear shape. We are studying Nesprin-related mechanisms essential for maintenance of robust muscle nuclear structure. Our recent studies identified intra-nuclear alterations in the distribution of chromatin elements and DNA within the muscle nuclei of Nesprin/MSP-300/Klar mutants. These proteins were shown to be essential for linking the nuclear membrane with the microtubule network, as well as with muscle sarcomeres, in order to maintain robust myonuclear shape. Furthermore, we have identified a novel membrane protein, (Muscle-specific-alpha2delta), which is essential for keeping Nesprin/MSP-300 in the nuclear membrane preventing its re-translocation to the ER. Live imaging of muscles within intact Drosophila larvae with fluorescently labeled nuclei and Z-lines enabled imaging of myonuclei during muscle contraction/relaxation waves. A general recovery of myonuclear shape is detected in the course of contraction/relaxation waves of wild type larvae. In contrast, mutant nuclei became fluidic and exhibited significant deformation. We suggest that this deformation is the basis for defects in the intra-nuclear organization of chromatin, which further leads to aberrant transcriptional alterations in the mutant muscles. Such alterations might represent the cause for the numerous muscle diseases associated with mutants of the LINC complex in humans.

Biography:

Haya Lorberboum-Galski is a full Professor of Biochemistry at the Department of Biochemistry and Molecular Biology, Institute for Medical Research Israel-Canada (IMRIC), Faculty of Medicine, the Hebrew University of Jerusalem, Israel. She has published over 60 publications in peer-reviewed journals in her fields of expert, as well as review articles and edited a book on chimeric proteins. She serves as an ad-hoc Referee for peer-reviewed journals. She is currently the Chairman of the Institute for Medical Research Israel-Canada (IMRIC).

Abstract:

Modern medicine offers no cure for genetic mitochondrial disorders and the usual treatment is mostly palliative. We developed a novel concept for the treatment of mitochondrial disorders using Cell/Organelle-Directed Protein Replacement Therapy; the delivery of a wild type mitochondrial protein/enzyme directly to its sub-cellular location and into its natural complexes, in the form of a fusion protein. Our approach is to fuse a wild type mitochondrial protein, including the Mitochondrial Targeting Sequence (MTS) with the delivery peptide TAT [HIV-transactivator of transcription (TAT) peptide], which will lead the protein/enzyme into the cells and their mitochondria, where it will substitute for the mutated endogenous protein. We tested this novel approach using a number of mitochondrial proteins, implicated in mitochondrial human diseases: Lipoamide Dehydrogenase (LAD), C6ORF66 and Frataxin were evaluated in vitro, in patients’ cells and in vivo, in mouse models. TAT-MTS-Mitochondrial fusion proteins are rapidly and efficiently internalizing into cells and their mitochondria both in patients’ cells and in mice tissues, including the brain. Treatment with the new TAT-MTS-Mitochondrial fusion proteins, improves mitochondrial functions and life span in animal models. Interestingly, when we replaced the MTS sequence of the exogenous protein with a heterogeneous MTS sequence, both mitochondrial penetration and biological activity significantly increased. This novel approach may open new inroads in the management of many incurable mitochondrial diseases.

Claire Wyart

Institut du Cerveau et de la Moelle épinière-UPMC CNRS, France

Title: Investigation of sensory interface relaying information from cerebrospinal fluid to motor circuits

Time : 14:50-15:10

Biography:

Claire Wyart has completed her PhD in Strasbourg, France and her Postdoctoral Fellowship in UC Berkeley, California, USA. She has trained in neuroscience, physiology and biophysics. She has started her lab in the Brain and Spine Institute in Paris in 2011. Her main interest is to unravel the circuits located in hindbrain and spinal cord that underlie locomotion. In particular, she has developed new optical and ontogenetic technologies to probe the role of sensory feedback during active locomotion.

Abstract:

The cerebrospinal fluid (CSF) is a complex solution circulating around the brain and spinal cord. Behavior has long been known to be influenced by the content and flow of the CSF, but the underlying mechanisms are completely unknown. CSF-contacting neurons by their location at the interface with the CSF are in ideal position to sense CSF cues and to relay information to the nervous system. By combining electrophysiology, optogenetics, bioluminescence monitoring with calcium imaging in vivo, we demonstrate that neurons contacting the CSF in the spinal cord detect local bending and in turn feedback GABAergic inhibition to multiple interneurons drives locomotion in the ventral spinal cord. Behavior analysis of animals deprived of this mechano-sensory pathway reveals its contribution in modulating frequency and duration of locomotion. Altogether our approach developed in a transparent animal model shed light on a novel pathway enabling sensory motor integration between the CSF and motor circuits in the spinal cord.

Biography:

Hila Toledano has received her PhD from The Weizmann Institute Israel (2003) and completed her Postdoctoral studies at the Salk Institute, San Diego CA (2012). She is a PI at University of Haifa, Israel and her lab is focused on post-transcriptional regulation of adult stem cells.

Abstract:

Highly regenerative tissues are supported by rare populations of tissue-specific stem cells that continuously divide to both self-renew and generate differentiated progeny. Aging is characterized by aberrant tissue regeneration that is attributed to deteriorated function of stem and its surrounding cells; however it is not clear whether this process is genetically regulated. Heterochronic microRNAs (controlling the timing of events) were initially described to control the timing of developmental stages; however their role in the regulation of aging is just beginning to be studied. Previously we have linked the role of the heterochronic miRNA let-7 to the declined function of the germline stem cell in aged Drosophila males. Our recent findings indicate that the expression of the evolutionary conserved miR-9a increases significantly during aging in both stem and progenitor germ cells. We further show that miR-9a directly down regulates the levels of N-cadherin, which is required to enable stem cells detachment from the niche. Thus we conclude that miR-9a promotes differentiation and attenuates tissue degeneration. Characterizing the microRNA based posttranscriptional regulatory network and its temporal modulation is critical towards understanding the role of regulation in driving and responding to aging.

Yu Haijun and Yunfeng Zhou

Zhongnan Hospital of Wuhan University, China

Title: Radio-sensitization of clioquinol and zinc ion in human cancer cells

Time : 15:30-15:50

Biography:

Yunfeng Zhou is a Professor of Radiation Oncology and he was the Dean of Medical School and the President of Zhongnan Hospital, Wuhan University. From 1986 to 1991, he studied for his Oncology Diploma (DIS) in Lyon, France. He has been working at the Department of Radiation Oncology and Medical Oncology as a Director of Hubei Cancer Clinical Study Center, Hubei Key Laboratory of Tumor Biological Behaviors and Hubei Radio-therapeutic Quality Control Center. His main research fields including radiation biology which focuses on the radio-sensitivity modified by telomere/telomerase and radiation-guided gene therapy of cancer. He has published more than 100 papers in international and national journals. Due to his outstanding contributions for Sino-France medical education exchange, the French Government awarded him French Knight Badge (2006) and National Order of the Legion of Honor (2009).

Abstract:

Objective: We have reported that the anticancer activity of Clioquinol and Zinc in different cancer cells, Clioquinol and Zinc can inhibit the cancer cell viability by down-regulation of NF-kb activity. Re-activation of NF-kb plays an important role in radio-resistance of human cancer cells. Here we investigated the radio-sensitization of Clioquinol and zinc in different human cancer cells.

Methods: The toxicity of 1 μM Clioquinol (CQ) and 10 μM ZnCl2 (Zn) in human cancer cells of Hep-2 and human normal cells MRC-5 was determined by MTS assay. The radio-sensitization of CQ+Zn in Hep-2 and Hela cells was detected by colon formation measure. The effect of CQ+Zn on the NF-kB activity in Hep-2 and Hela cells is measured by the luciferase activity assay. The ATM RNA and protein expression level were determined by RT-PCR and Western blot methods.

Results: The cell viability of Hep-2 and MRC-5 treated with 1 μM CQ and 10 μM Zn for 72 hours were 104.0% and 114.3% respectively compared to the control groups (Hep-2 cells: CQ+Zn vs. Control, P=0.8850; MRC-5 cells, CQ+Zn vs. Control, P=0.8204). Colon formation measure indicated that 1 μM CQ and 10 μM Zn can significantly enhance the radio-sensitivity of Hep-2 and Hela cell (Irradiation group vs. Irradiation+CQ+Zn group: P<0.001 in Hep-2 cells and P<0.001 in Hela cells), SERSF2 for Hep-2 and Hela were 1.33 and 1.75 respectively. One μM CQ and 10 μM Zn inhibited the activity of NF-kB after 2 Gy γ-Ray irradiation in Hep-2 and Hela cells (Irradiation group vs. Irradiation+CQ+M Zn group: For Hep-2 cells, 151.10% vs. 108.60%, P<0.001; for Hela cells, 156.30% vs. 104.20%, P<0.001). We further detected the ATM mRNA and protein expression level after 2Gy irradiation with or without pre-treatment of 1 μM CQ and 10 μM Zn for 6 hours. ATM mRNA expression level in Hep-2 after 24 hours of irradiation in the group of with the 1 μM CQ and 10 μM Zn was 67.78% of that in the irradiation along group (P=0.017). ATM protein expression level after 48 hours of irradiation in the group of with the 1 μM CQ and 10 μM Zn was 69.38% of that in the irradiation along group (P=0.039).

Conclusion: Clioquinol and zinc can enhance the radio-sensitivity of human cancer cells, the inhibition of NF-kB and ATM may mediate the radio-sensitization in human cancer cells.

Avinash Patel

Max Planck Institute of Molecular Cell Biology and Genetics, Germany

Title: Dissecting the mechanisms of liquid to solid phase transition associated with neurodegenerative diseases

Time : 15:50-16:10

Biography:

Avinash Patel has completed his PhD from the Manchester Cancer Research Institute, UK in 2012. He is currently pursuing Post doctoral research in the lab of Prof Tony Hyman, Max Planck Institute for Cell Biology and Genetics, Dresden, Germany. He has recently published a paper in the journal Cell, which showed general principles underlying Liquid-to-Solid phase transitions might be a key mechanism behind neurodegenerative diseases.

Abstract:

FUS/TLS is a prion-like protein that contains intrinsically disordered domains and is associated with neurodegenerative disease. We recently showed that intracellular FUS/TLS compartments form under various cellular conditions and that these compartments exhibit liquid-like properties in vivo and in vitro. “Aging” experiments revealed that FUS/TLS liquid droplets undergo a phase transition to a solid-like state which is accelerated by disease mutations. We discovered that concentrating proteins by phase separation comes with the trade-off that can also promote protein aggregation. Solid-like aggregates of prion-like proteins are a hallmark of many aging-associated diseases. Aberrant phase transitions might be one trigger causing aging-associated diseases. However, the molecular mechanisms underlying this aberrant phase transition and the strategies cells have developed to sustain the function of these aggregation-prone proteins remain largely enigmatic. Here, we present recent advances we made in understanding the mechanisms cells might have developed to prevent the liquid-solid phase transitions by using a wide range of biochemical, biophysical and cell biology techniques. We find that electrolytes, small compounds and protein interactors affect the liquid-liquid, as well as liquid-solid transitions. Insights gained from studying liquid-solid phase transition might help us developing drugs targeted to treat age-associated diseases.

Chasserot-Golaz Sylvette

Institute of Cellular and Integrative Neurosciences, France

Title: Actin and annexin A2: Essential partners of neuroendocrine secretion

Time : 16:25-16:45

Biography:

Chasserot-Golaz Sylvette has completed her PhD from University of Strasbourg, France which is centered on the mechanism of action of steroids antiglucocorticoids in hepatocytes and hepatoma cells at Institut de Biologie Moléculaire et Cellulaire (IBMC) in 1985. She has been working as a permanent Research Scientist at INSERM since 1988 and moved to the Institut des Neurosciences Cellulaires et Intégratives (INCI) in Strasbourg in 1993 where her research is dedicated to elucidating the molecular mechanisms underlying exocytosis in neuroendrine cells. She is an expert in the molecular and cellular implication of annexin A2 in chromafin cells and more generally in cellular neurobiology. She has published more than 84 papers in renowned journals.

Abstract:

The neuroendocrine system depends on elaborate cellular communication provided by intense membrane trafficking. Calcium regulated exocytosis results in the release of molecules such as neurotransmitters and hormones contained in secretory granules. In neuroendocrine cells, the recruitment and subsequent fusion of secretory granules at the plasma membrane occur at specific sites dedicated to exocytosis. Annexin A2 was the first protein identified at these exocytotic sites in chromaffin cells. It binds two major actors of exocytosis, actin and phospholipids and mediates the formation of lipid microdomains required for the spatial organization of fusion sites at the plasma membrane. To understand how annexin A2 promotes this membrane remodeling, the involvement of cortical actin filaments in lipid domain organization was investigated. Electron tomography of chromaffin cells, together with amperometric measurements of single cell catecholamine release showed that cortical actin bundled by annexin A2 connects docked secretory granules to the plasma membrane and contributes to the formation of GM1-enriched lipid microdomains at exocytotic sites. When an annexin A2 mutant with impaired actin filament-bundling activity was expressed, the formation of plasma membrane lipid microdomains and the number of docked granules decreased and fusion kinetics slower, whereas the pharmacological activation of the intrinsic actin-bundling activity of endogenous annexin A2 had the opposite effects. Thus, annexin A2-induced actin bundling is essential for generating active exocytotic sites. Our results reveal that annexin A2 and the actin cytoskeleton are essential partners in the formation of lipid platforms for granule docking and fusion. This challenges the classical passive role depicted for the cortical actin cytoskeleton in calcium-dependent exocytosis and represents a major advance in our understanding of neuroendocrine secretion.

Jamila Chakir

Laval University, Canada

Title: Tissue engineering concept of a model of airway bronchial mucosa

Time : 16:45-17:05

Biography:

Jamila Chakir is a full Professor at the Department of Medicine at Laval University and Institut Universitaire de Cardiologie et Pneumologie de Québec. She has obtained her PhD degree in Immunology in France. She has received her Postdoctoral research training at Laval University and McGill University, Canada in inflammation and remodeling in asthma. Her research focuses on cellular and molecular mechanisms of airway remodeling particularly the role of structural cells in airway remodeling and their interaction with and inflammatory cells. She has published more than 200 papers, communications and book chapters in the respiratory and immunology field and holds grants from Canadian agencies. She is a Member of different national and international scientific committees and has received several awards from national and international organisms.

Abstract:

Asthma is an inflammatory disease characterized by an injury-repair cycle in the bronchial wall leading to airway remodeling. Cellular interactions between epithelial cells and underlying fibroblasts play a key role in this remodeling. The available information on resident cells in the bronchial mucosa were obtained from studying fixed bronchial biopsies or from studies conducted on cells grown in monolayers. However, isolated cells can only simulate a small part of the body’s complexity and often lose their morphology and functional properties. Tissue engineering is a field, which applies the principles of biology and engineering to the development of functional substitutes for damaged tissue. The two major goals of tissue engineering are the production of functional tissues that can be grafted into human and the development of in vitro models that are superior to conventional cell cultures mainly because monolayer cultures lack an adequate extracellular matrix. These in vitro models offer the possibility to study different mechanisms involved in many diseases such as asthma. We developed a bronchial mucosa model by tissue engineering using primary fibroblast and epithelial cells isolated from normal and asthmatic human bronchial biopsies. We observed that this model exhibits morphological, histological and functional features of bronchial mucosa. In engineered tissue from normal volunteers, fibroblasts were well organized in the extra-cellular matrix and the epithelial cells proliferate and differentiated to produce a pseudo-stratified structure. Epithelial cells and fibroblasts in this model were able to produce basement membrane proteins. This confirmed that there was functional in vitro cooperation between cells through laminin and type IV collagen synthesis. We used this model to study communication between inflammatory and resident bronchial cells. We found that T cell survival was greater in asthmatic engineered bronchial mucosa and that epithelial cells are more effective than fibroblasts in ensuring T cell survival. We also showed that fibroblasts from asthmatic subjects regulate epithelial cell proliferation and TGF-β signaling may represent one of the pathway involved in these interactions. This sophisticated three dimensional model could be a valuable tool to a better understand key mechanisms involved in inflammation and airway repair in asthma

E. Sacide Çaglayan

Yıldırım Beyazıt University, Turkey

Title: Importance of Myc-related microRNAs in induced pluripotency

Time : 17:05-17:25

Biography:

E Sacide Caglayan has completed her PhD on Medical Genetics in Afyonkocatepe University in 2010 and worked as a Visiting Scholar on induction of pluripotency from fibroblasts by using microRNAs in Ruohola-Baker Lab, Institute of Stem Cell and Regenerative Medicine in University of Washington. Presently, she is working as an Assistant Professor in Health Science Faculty, Yildirim Beyazit University, Turkey.

Abstract:

Pluripotent stem cells (PSCs) have the capacity to differentiate into any cell type of the body. Therefore, induced pluripotent stem cells (iPSCs) are seen as a promising solution for patient-specific cell therapies. However, the safety is major issue for in vitro methods that are used in induction of pluripotency and also in differentiation of PSCs toward specific cell types. In pioneer studies of iPSC generation, the role of c-Myc has been highlighted as a possible master regulator of pluripotency, but direct c-Myc overexpression is known to prompt drawbacks, especially in human cells. In recent studies, the role of non-protein coding RNA molecules such as microRNAs (miRNAs) has been shown in enhanced reprogramming efficiency. In addition, new reprogramming methods have been ultimately improved by adding miRNAs, in the absence of previous factors. Cross interaction between miRNAs and c-Myc has been also found in differentiation of iPSCs, as well as in reprogramming and self-renewing the pluripotent state. Thence, miRNAs are promising solution for efficiency and safety of iPSC derivation and differentiation methods. The purpose of the present review is to evaluate interaction mechanisms of miRNAs with c-Myc and in iPSC technology.

Yu Liu

Zhongnan Hospital of Wuhan University, China

Title: Neogenin expression may be inversely correlated to the tumorigenicity of human lung cancer

Time : 17:25-17:45

Biography:

Yu Liu is currently working as an Associate Professor in the Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China. Her research interests include the study of key signaling pathways involved in liver metastasis of colorectal cancer by exploring the molecular mechanisms mediated filopodia growth of tumor cells to provide new thinking direction and theoretical basis for effective prevention and treatment of colorectal cancer liver metastases. She also works on the study of key proteins involved in the communications between stomach cancer cells and bone lesion to investigate the mechanism of pre-metastatic communication between primary tumors and bone.

Abstract:

Despite advanced screening technology and cancer treatments available today, metastasis remains an ongoing major cause of cancer-related deaths worldwide. Typically, lung cancer is one of the cancers treatable by surgery in conjunction with chemotherapy when it is detected at an early stage. However, it still ranks as the highest modality and mortality of cancer types in the world and this is mostly due to a recurrence of metastatic lung cancer post-resection of the primary malignancy. Lung cancer metastases predominantly occur in the liver and bone and yet the molecular mechanisms that regulate these organ-specific lung cancer metastases are largely unknown. Therefore, the identification of any critical molecule, which triggers malignancy in lung cancer, would be an excellent target for treatment. There is growing evidence that cytoskeletal proteins and actin-based protrusions have central roles in cancer biology, particularly in metastasis. Our previous study showed neogenin, a receptor of chemotropic neuronal guidance molecule Netrin, can directly interact with myosin X, one of key filopodia regulators and regulates in myosin X movement and functions in inhibition of filopodia formation. However neogenin's relationship to tumorigenesis remains to be elucidated. We report here neogenin expression in human lung cancer samples and its association with different clinicopathologic characteristics relationship. Immunohistochemically, compared with adjacent normal tissues, neogenin staining was significantly lower in tumor tissues (P<0.001). Loss of neogenin sub-cellular localization in lung cancer tissue was correlated with pathological stage, differentiation extent (P<0.001), but not with the age or smoking history, lymphatic invasion, vascular invasion, pleural invasion and gender (P>0.05). Conversely, RGMc, one of ligands of neogenin, expression is not differential between lung cancer tissue and normal tissue. More importantly, membranous staining of neogenin was significantly correlated with a better overall survival of either stage I or stage II/III lung cancer patients and multivariate analysis confirmed that membranous expression of neogenin was an independent positive prognostic indicator (P<0.05). Together, these observations establish neogenin may play a role in lung carcinogenesis as well as morphogenesis and the expression may be inversely correlated with lung carcinogenicity. It is valuable as a potential prognostic factor.

Jun Wu

Southeast University, China

Title: Proteolytic maturation of Drosophila neuroligin3 in central nervous system

Time : 17:45-18:05

Biography:

Jun Wu is currently pursuing PhD in Life Science at Southeast University, China. His research interest focuses on the molecular mechanism of neurological disorder diseases, such as autism spectrum disorders.

Abstract:

Neuroligins are postsynaptic adhesion molecules that are essential for synaptic function and regulation by binding to their presynaptic ligands, Neurexins. Mutations in neuroligin and neurexin genes have been implicated in cognitive diseases such as autism. Previous study shows more than two isoforms of endogenous neuroligin3 in Drosophila. Here, we report that Drosophila neuroligin3 (DNlg3) is proteolytically activated in the central nervous system specifically, which is essential for an interesting behavior. A protease belonging to ADAMs (a disintegrin and metalloproteinases) family is responsible for DNlg3 processing in vivo and in vitro. Interestingly, as a membrane protein, DNlg3 is processed intracellularly rather than at the cell surface. DNlg3 is cleaved at its extracellular AchE-like domain to generate the N-terminal fragment (NTF) and the cleaved membrane-anchored fragment (cDNlg3). After cleavage, the cDNlg3 rather than full-length (FL) or NTF can rescue defect in DNlg3 mutants, suggesting that proteolytic cleavage of DNlg3 is required for keeping normal behavior. Our study broadens our knowledge of the scope of Neuroligins function, as well as provides a novel cleavage paradigm for studying other membrane proteins.

Arezou Pakfar

Islamic Azad University, Iran

Title: Chondrogenic and possible pathologic effects of PRP on adipose derived

Time : 18:05-18:20

Biography:

Arezou Pakfar holds a Master degree in Cellular and Molecular Biology at Islamic Azad University, Iran. Her thesis was about Tissue Engineering and Stem Cells. She is currently working as a Researcher at Stem Cell Technology Research Center since 2014.

Abstract:

Introduction: Application of activated Platelet-Rich Plasma (PRP) with its vast range of cytokines and growth factors has achieved a considerable attention for chondrogenic differentiation in tissue engineering fields. Therefore, the aim of this study was to investigate the effects of PRP on human adipose derived MSC chondrogenesis.

Material & Methods: MSCs were differentiated using different PRP concentrations (5% and 15%). Changes in gene expression levels for cartilage and bone specific markers (COLII, AGC, SMAD2, SOX9) and (RUNX, Osteocalcin), respectively, were appraised by real time PCR. Also chondrogenesis was assessed by measuring secreted glucosaminoglycan in the medium or that kept in cell ECM. The expression of pathologic markers was evaluated by measuring the VEGF, TNFα secretion and alkaline phosphatase activity and calcium deposition.

Results: The most secreted VEGF (p<0.05) in 5% and 15% concentration were anti-angiogenesis. The inflammation factor (TNF-α) quantity of 5% PRP was the lowest (p<0.05) on 21st day but chemotaxic characteristics of the mentioned group was the highest. The expression levels of AGC, SOX9, COLII and RUNX were significantly (p<0.05) down-regulated while Osteocalcin was up-regulated. In addition, hypertrophy was seen in chondrogenic differentiation.

Conclusion: Due to having vast range of biologic active factors, PRP based chondrogenesis of human adipose derived MSC is dose dependent and the undesired outcomes due to absence of regulatory factors, should be suppressed by further optimizing the formulation of chondrogenic differentiation media.

Biography:

Mohammed Nabih Baeshen is an Assistant Professor of Genomics and Biotechnology, Department of Biology, Faculty of Science, University of Jeddah since 2014 to till date. He has completed his PhD in 2010 from King Abdulaziz University (KAU) and been assigned as an Assistant Professor at the Department of Medical Laboratories at the Faculty of Health Sciences, KAU. He was also assigned as Consultant in the Center of Nanotechnology at KAU. He has three reference books in practical and theoretical introductory biology and up to 29 publications to his credit.

Abstract:

Rhazya stricta is a popular plant used in folkloric medicine around many parts of Asia. Recent studies proved its medicinal properties against many diseases, inflammations and abnormal conditions. Many in vivo and in vitro studies showed the ability of plant extracts against different types of cancer. Our study is representing new records and novel techniques were first used for R. Stricta. All previous studies used whole leave extracts and alkaloidal fractions according to their famous medicinal reputation, while our present study also showed a cytotoxic effect of the non-alkaloidal fraction of the leaf extract against breast cancer MFC-7 cell line. On the other hand, we introduced in our study for the first time the cytotoxic effect of the biosynthesized extracts of R. Stricta leaves with gold nanoparticles against MFC-7 cell lines as aqueous whole extract, alkaloidal and non alkaloidal fractions of the extract. MTT test results showed cytotoxic effect of all nano-biosynthesized plant extracts when compared to non treated control group as represented by the percentage of cell death as follows: 82% non-alkaloidal fraction, 70% alkaloidal fraction, 52% whole aqueous extract and 0% for the control group. These results showed that the fractionations of the plant extracts were more effective than the whole aqueous extract against MFC-7 cell line and non-alkaloidal fraction as not expected gave the strongest effect against MFC-7 cell lines. In conclusion, our results were promising for the treatment of cancer and we recommend to apply it more in vivo and in vitro studies against more types of cancer with more experiments of the biosynthesis of R. stricta extracts alone or mixed with other medicinal plant extracts with more types of nanoparticles in different physical and chemical conditions to get the best results for this promising plant.