Conference Schedule

Day1: August 20, 2018

Keynote Forum

Biography

Richard Harbottle undertook his Undergraduate degree in Biochemistry from the University of St.Andrews in Scotland and subsequently joined a Gene Therapy group at Imperial College London where he did his MSc in Human Molecular Genetics and a PhD in the Development of Non-Viral Gene Therapy. He is currently the Principle Investigator and Group Leader of the DNA Vector Research Group at the German Cancer Research Centre (DKFZ) in Heidelberg. His research focuses on the development of DNA technologies for gene and cell therapy with particular focus on the application of minimally sized DNA vectors which can autonomously replicate within cells without causing any genetic or molecular damage.

Abstract

The research of the DNA Vector Lab has most recently focused on the development of a next-generation non-viral DNA vector for gene and cell therapy and the genetic modification of cells. We have successfully built a novel DNA vector platform, which is uniquely suited for this purpose; it provides persistent expression and episomal maintenance without the use of potentially toxic viral components or the risk of insertional mutagenesis. We have demonstrated for the first time that non-integrating non-viral DNA vectors can be used comparably in applications to integrating vector systems such as Lentiviral and Sleeping Beauty vectors and with genome editing systems such as CRISPR; in some instances, our DNA vectors can be used where viruses cannot. We are applying our DNA vectors for gene therapy, for the generation of isogenic cell lines for tumour modelling and the genetic modification and therapeutic correction of clinically relevant human cells. We have recently made a breakthrough in our DNA vector design which allows the application of our vector in stem cells and primary human cells. For the first time, a non-integrating vector system can provide persistent transgene expression in primary human T-cells without the risk of integration-mediated genotoxicity, and we are currently developing a range of novel DNA vectors for anti-tumour immunotherapy. These DNA vectors can also be used to genetically modify stem cells, and we have recently shown that we can generate stable mouse embryonic cell lines and can generate transgenic mice from these modified cells. This presentation will illustrate the features of these novel DNA vectors and how we intend to leverage this new DNA Vector platform in projects which encompass T-Cell immunotherapy, stem cell therapy and prophylactic gene therapy for cancer.

Biography

Jan Lukas Robertus has received his MD at the University of Utrecht and completed his PhD and Registrar program in Pathology at the University of Groningen, the Netherlands. He was appointed as a Consultant Cardiothoracic Pathologist at The Royal Brompton and Harefield NHS Foundation Trust in February 2015. He has previously worked as a Consultant Cardiothoracic Pathologist at the Erasmus Medical Centre, Rotterdam, The Netherlands.  He is the Lead Pathologist for computational pathology. He is also Co-lead for the Royal Brompton Cardiac Morphology Unit and is Member of the Brompton Cardiac Morphology Steering Committee. He is Honorary Senior Clinical Lecturer at the National Heart and Lung Institute, Imperial College London. His main research interests are Computational Pathology, Specifically in the Areas of Thoracic Oncology, Cardiomyopathies, Aortopathies, Cardiac and Pulmonary Transplantation.

 

Abstract

There is an urgent need for alternative methods to objectively diagnose and classify tumours and for identification of significant new tumour subtypes. Computational pathology offers an opportunity for consistent and automated evaluation and stratification of tumour phenotype. Although knowledge of the molecular basis of tumours is rapidly increasing, histomorphology based diagnostic subtyping and recognition of new subtypes remains dependent on the subjective and limited morphological diagnosis of expert pathologists. The limitations of this classical approach are demonstrated in the inter-observer reproducibility that generally shows acceptable k-values only for typical tumour growth patterns and when expert opinion is obtained. Deep learning approaches in computational pathology have already shown excellent performance in a range of image classification challenges, and are set to revolutionize biomedical research, clinical practice, and the healthcare industry. Artificial Intelligence (AI) applications, for example using convolutional neural networks, can analyse and grade tumour tissue biopsies; a task currently performed by pathologists. Similarly, computational pathology and concurrent deep learning approaches are also creating novel tools to link mutational status and gene expression to phenotype. Deep learning in computational pathology has been shown to be able to identify prognostic factors and determine genotype-phenotype correlations in various types of cancer. Computational pathology and OMICS are part of an integrative approach that is set to accelerate our ability to interrogate biologically relevant pathways in cancer. This will require a multidisciplinary approach of pathology, computational science, mathematics, molecular biology and clinical data. Ultimately, computational pathology and it’s applications in AI will lead to improved options for individualized therapy and accelerate the future development of new treatment pathways.

 

Biography

Magnus S Magnusson is a Research Professor at University of Iceland. He has completed his PhD in 1983, University of Copenhagen. He is the Author of the T-pattern model regarding real-time organization of behavior. He Co-directed a DNA analysis, numerous papers, talks and keynotes at international mathematical, neuroscience, proteomics, bioinformatics and religion conferences.  He was Deputy Director (1983-1988) in the Museum of Mankind, Paris. He is Invited Professor in Psychology and Biology of Behavior at the University of Paris (V, VIII, XIII). Since 1991, he is the Founder and Director of the Human Behavior Laboratory in formalized collaboration with 32 European and American universities based on Magnusson’s analytical model initiated at University Paris V, Sorbonne, in 1995.

 

 

Abstract

Beginning in the early 1970’s, this longstanding primarily ethological (i.e., biology of behavior) project concerning social interaction and organization in social insects and primates including humans, was initially inspired mainly by the work of N. Tinbergen, who with K. Lorenz and von Frisch shared the Nobel Prize in Medicine or Physiology in 1973 for their ethological research and discoveries. The smallest creatures they studied were social insects and there was no mentioning of self-similarity or any nanoscale actors or of cell societies (better named protein societies). The work on this project focusing on pattern definitions has resulted in the self-similar fractal-like T-pattern recurring with statistically significant translational symmetry, resulting also in the creation of the special purpose software THEMETM (hbl.hi.is and www.patternvision.com) allowing their abundant detection in animal and human interactions and later in neuronal interactions, showing T-patterned self-similarity of interaction between and within brains. T-patterning in DNA and proteins was then noticed. Moreover, T-pattern based self-similarity in social behavior and organization from Cell City (protein cities) to the very recent and only large-brain mass-societies; those of modern humans. Not existent in the mass-societies of insects (hives) and cells (animal bodies), in protein and human mass societies long T-patterned strings external to and more durable than the citizens, are essential. That is, strings of molecules in protein cities, but of letters in human cites after the gradual but fundamental invention of writing and standardized and massively copied, distributed, promoted and enforced letter strings (texts) called legal or holy and finally allowing the development of modern science and technology and mass-societies. Human and protein citizens formed with external T-patterned strings are now known to do string controlled social work in complex societies, such self-similarity from nano to human mass-social scales providing possibilities of deeper understanding.

 

Tracks

  • Genetics & Genetic Engineering | Human Genetics & Genetic Disorders | Gene Mutation and Cloning | Immunology & Immunogenetics | Plant Genetics | Bioinformatics in Genetics | Immunotherapy | Next Generation Sequencing | Stem Cell Therapy | Regenerative Medicine
Location: Meeting Place 1
Speaker

Suzanne A Al Bustan

Kuwait University, Kuwait

Chair

Biography

Suzanne Al-Bustan has completed her PhD in Human Genetics from the Duncan Guthrie Institute in Medical Genetics at Glasgow University in 1992. She is an Associate Professor of Human and Molecular Genetics in the Department of Biological Sciences and currently the Department Chair of Biological Sciences. She has published numerous papers in reputed journals and has been active in both scientific research and supervision of several graduate students in the areas of human genetics and molecular biology.  Her main research interests are in the Genetic Association of Candidate Genes with Complex Traits, specifically Dyslipidemia and Subsequent Disorders. The methods applied include re-sequencing of genes involved in the lipid transport (APO gene family) and metabolism (LPL) in order to identify variants that may increase the risk to develop dyslipidemia.

 

Abstract

Interethnic genetic differences play a role in plasma lipid level variation across populations. Several genes involved in lipid metabolism and transport are candidates for the genetic association with lipid level variation including lipoprotein lipase (LPL). This enzyme is important for the hydrolysis of circulating triglycerides into free fatty acids for tissue utilization. It is encoded by a 30 Kb gene, mapped to chromosome 8p22. More than 1000 variants have been identified across the gene including both SNP’s and InDel’s with variable frequencies across different populations. The objective of the study was first to identify variants across the LPL gene among a sample of Kuwaiti’s of Arab ethnicity and investigate the genetic association of selected variants with variation in lipid levels among a cohort of 712 apparently healthy Kuwaiti’s. The variants were identified by re-sequencing the full gene in 100 sample of Kuwaiti’s with document Arab ethnicity. A total of 293 variants were identified and characterized among which were 47 novel variants. The study was the first to report a genetic association of a novel “rare” variant (LPL: g.18704C>A) with a significant increase in serum TG (p=0.044) and VLDL (p=0.043) levels. In addition, the variant also showed a significant (p=0.033) association of lower high-density lipoprotein (HDL). The opposing effect of one variant on two lipid levels can be explained by the direct action of LPL on TG levels and indirect action on HDL levels (Figure 1). This newly identified variant (g.18704C>A) should be investigated in other populations for its genetic association with serum lipid levels to verify if it is ethnic specific and its role in the gene expression regulation of pathways involved in lipid metabolism and transport. Moreover, the study verified the importance of identifying ethnic specific variants that would explain the interethnic variation in lipid levels.

 

 

 

Biography

Jun Dou now is a Director, Professor of Department of Pathogenic Biology and Immunology, School of Medicine, Southeast University. He got his Medicine Doctor degree (MD, PhD) in 1997 at Zhejiang University of China. He visited the Ulm University School of Medicine, Germany as a Visiting Scholar from Jun’ 1999 to Sep’ 1999, and then visited the CDC, USA as a Senior Visiting Fellow from Oct’ 2001 to Feb’2004. He also visited the Georgia State University, USA as a Visiting Fellow from Sep’ 2006 to Dec’2006. Recently, he twice visited the Yale University School of Medicine, USA as a Senior Visiting Fellow in 2014 and in 2015. Currently his research has focused on targeted toward cancer stem cells (CSCs) by manipulating nc-RNAs for treating breast, ovarian, colon cancers and melanoma. He also continues research in CSC vaccines and CSC nanotheranostics in treating cancers.

 

Abstract

Tumor vaccines offer a number of advantages for cancer treatment. In the study, the vaccination of cancer stem cells (CSCs) with high expression of the type I receptor tyrosine kinase-like orphan receptor (ROR1) was evaluated in a murine model for the vaccine’s immunogenicity and protective efficacy against epithelial ovarian carcinoma (EOC). CD117+CD44+ CSCs were isolated from human EOC HO8910 cell line using a magnetic-activated cell sorting system; murine ID8 EOC suspension sphere cells, which are collectively known as cancer stem-like cells, were aquired from serum-free suspension sphere-forming culture. Mice were subcutaneously immunized with the repeat cycles of freezing and thawing whole HO8910 CD117+CD44+CSC and ID8 cancer stem-like cells, respectively, followed by a challenge with EOC cells at one week after final vaccination. The efficacy of CSC vaccine was observed in that the CSC vaccination induced significantly immunity against EOC growth, and markedly prolonged survival of EOC bearing mice in the prophylactic setting compared with non-CSC vaccination. Flow cytometry showed significantly increased immunocyte cytotoxicities and remarkablely reduced CSC counts in the CSC vaccined mice. Moreover, the protective efficacy against EOC was decreased when the ROR1 expression was down-regulated by shRNA in CSC vaccines. The findings from the study suggested that CSC vaccines with high ROR1 expression were highly effective in triggering immunity against EOC in vaccinated mice and may serve as an effective vaccine for EOC immunoprophylaxis.

Biography

Sudha Bansode is a Associate Professor in Zoology at Shankarrao Mohite College, Akluj, Maharashtra State , India. Recently she has completed her Post Doctoral Studies at University of California, Riverside, USA. She is a active researcher & passionate teacher in India. Still she has been published above 25 research papers in International Journals & she is interested on Bone Research. Also she has honor of Distinguished Editorial Board Member of several International Journals. She is a own author of “Textbook Histological Techniques” & “Outlines of Physiology”. And now she is working on another own reference book “Rhythms in Freshwater Crustaceans”. She is a University recognized research guide for Ph.D. students in India.

 She was a invited Indian Speaker of “OXFORD SYMPOSIUM” on 27-29 August, 2014 at Balliol College, Oxford, United Kingdom & CELL SIGNALING & CANCER THERAPY – International Conference at Double Tree, Hilton Chicago on 27-28 September 2017. She was academic visitor of Bangkok- Thailand, Colombo-Sri Lanka, Daira-Dubai-UAE. Her recent intellectual Interaction is with many International Professional groups.

 

Abstract

Genes are understandably crucial to physiology, morphology and biochemistry, but the idea of genes contributing to individual differences in behaviour once seemed outrageous. Nevertheless, some scientists have aspired to understand the relationship between genes and behaviour, and their research has become increasingly informative and productive over the past several decades. At the forefront of behavioural genetics research is the fruitfly Drosophila melanogaster, which has provided us with important insights into the molecular, cellular and evolutionary bases of behavior. By employing this development in their experiments with laboratory fruit flies, Gantz and Bier demonstrated that by arranging the standard components of this anti-viral defense system in a novel configuration, a mutation generated on one copy of a chromosome in fruit flies spreads automatically to the other chromosome. The end result, Bier says, is that both copies of a gene could be inactivated “in a single shot.”

The two biologists call their new genetic method the “mutagenic chain reaction,” or MCR. “MCR is remarkably active in all cells of the body with one result being that such mutations are transmitted to offspring via the germline with 95 percent efficiency. Thus, nearly all gametes of an MCR individual carry the mutation in contrast to a typical mutant carrier in which only half of the reproductive cells are mutant.”

Bier says “there are several profound consequences of MCR.  First, the ability to mutate both copies of a gene in a single generation should greatly accelerate genetic research in diverse species.  For example, to generate mutations in two genes at once in an organism is typically time consuming, because it requires two generations, and involved, because it requires genetic testing to identify rare progeny carrying both mutations.  Now, one should simply be able to cross individuals harboring two different MCR mutants to each other and all their direct progeny should be mutant for both genes.”

 

Biography

Iman Yousefi Javan has completed his PhD from Tuscia University (University of Viterbo in Italy). His graduation course is Plant Biotechnology and he was the winner of the scholarship in Italy (in years 2009 & 2010). He is Head of Department and Assistant Professor of Torbat Heydarieh University in Iran (Department of Plant Production, Faculty of Agriculture), which is one of Iranian leading University. He has published more than 10 papers in reputed journals and has been serving as an Editorial Board Member of repute. He is Academic Staff in Torbat Heydarieh University since 2014. Having a special interest in application of new methods in genetic plants resources, here he is working about of Drawing genetic map of the Tetraployid wheat. He is Member of Iranian Agriculture and Natural Resources Engineering Organization (M.n. 1008506996); Food and Agriculture Organization (FAO) (M.n. CSCP);  Iranian Science Agronomy and Plant Breeding Association (M.n.3502); International Society for horticultural science; Member of ABRII (Agriculture Biotechnology Research Institute of Iran).

Abstract

One of the most valuable and irreplaceable ones all over the world is Saffron. Saffron is the dried stigmas of Crocus sativus L. (Iridaceae) and the most precious and expensive spice. Due to the presence of water soluble carotenoid derivatives in saffron which are known to have antioxidant, anticarcinogenic and antitumors activities, this spice is often used for medicinal purposes. Saffron has three major carotenoid derivatives crocin, picrocrocin and safranal that are responsible for its intense color, bitter taste and aroma, respectively. In the pathway for making crocin, it possesses many enzymes which are catalyzes the reactions and are coded by related key genes. This research aim was to identify, isolate, and characterize LycB, CCD, CI, ZDS, PSY, IPP genes that was done by comparing with other genomes and protein sequences of these genes in other plants. Genomic DNA and cDNA was extracted from stigma organs, after designing specifc primers of these genes, using reference nucleotide sequence and carrying out PCR for gene amplifcation, the product of reaction was electrophoresed on the agarose gel. The resulting bands were isolated and characterized from the saffron genome. All exon and introns were identified from the crocetin component genes. After comparison between the sequenced fragments of nucleotide and the reference genome revealed, and also blasting sequences, we observed that there is a very similar resemblance between the crocetin encoding genes with few nucleotide differences between fragments (point mutations) which did not make a difference, in amino acids and ultimately in proteins.

Biography

Huanxiang Zhang has completed his PhD from Beijing Normal University, China and Post-doctoral studies from Geneva University School of Medicine, Switzerland. He is now working in the Department of Cell Biology, Medical College of Soochow University, China. His research focuses on the Control of the Directed Migration and Differentiation of Stem Cells, including neural stem cells, mesenchymal stem cells and embryonic stem cells, and tissue engineering, especially the interaction between stem cells and the silk fibroin scaffolds with a variety of physical and chemical properties. Recently, his group demonstrated the close relationship between the chemotactic migration of stem cells and their differentiation states, and further systematically studied the underlying mechanisms, thereby shedding light on optimization of the therapeutic potential of stem cells to be employed for tissue regeneration after injury.

 

Abstract

Precise migration of stem cells is crucially important for embryonic development, homeostasis in adults, and tissue repair after injury. However, the detailed mechanisms of the directed migration of these cells are not clear. Given the fact that only a very limited number of transplanted cells successfully reach the injured tissues, which severely restricts their clinical applications; further understanding of the cellular and molecular events underlying the directed migration of these cells will help to improve the application of stem cells as therapeutic vehicles. The multipotent mesenchymal stem cells (MSCs) with the ability to self-renew and differentiate into a variety of tissue cells have emerged as a promising source for cell-based therapies. In an effort to find a population of MSCs with strong migratory capacity, especially in response to growth factors or cytokines that are released from the injury sites and that act as chemo attractants to stimulate the directed migration of MSCs, our work has been focusing on the relationship between the chemotactic responses of MSCs and their differentiation status, as well as the delineation of the underlying regulatory mechanisms. Results showed that MSCs in varying differentiation states display different chemotactic responses to a variety of chemo attractants, such as hepatocyte growth factor (HGF). In this talk, I will summarize our data regarding the regulatory effects of PI3K/Akt, MAPKs, microRNAs, and beta-catenin signalling on the differentiating MSCs that undergo chemotaxis.

 

Biography

Gabrielle Bradshaw has a BSc (Hons) in Molecular Medicine and Haematology from Wits University, South Africa, a Master’s in Medical Research/Genomics from Griffith University, Australia, and  is currently a final year PhD Candidate at Queensland University of Technology in Brisbane, Australia. She is a qualified Medical Laboratory Scientist (Nat. Dipl in Biomedical Technology from University of Johannesburg, South Africa with experience working full time for the National Health Laboratory Service in Johannesburg, and part-time in the Molecular Genetics pathology laboratory at the Royal Brisbane and Women’s Hospital for Queensland Health. She has so far published 3 first-author papers in her research area of non-Hodgkin lymphoma and primary immunodeficiency, and she has an interest in Personalised Medicine, Diagnostic Genomics, and Gene Therapies to treat Cancer and Congenital Diseases.

Abstract

Aims: We aimed to use next generation sequencing to identify the molecular aetiology of a primary immunodeficiency disorder present with persistent lymphopaenia and neutropaenia, and to develop an in vitro rescue phenotype strategy. 
 
Methods: Whole exome sequencing was performed on a proband and his parents on the Ion Torrent platform at a read depth of 20X with target base coverage of 94.63%. Trio analysis was performed on the Ion Reporter Suite where variant annotation identified included SNPs and indels for each exome library. Confirmation of the causative role of the candidate gene was performed by qPCR and Western Blot analyses on the proband, family members and healthy control. We will further develop an in vitro proof-of-principle rescue phenotype strategy to correct the causative mutation in proband lymphocytes using CRISPR/Cas9 ribonucleoprotein (RNP) technology.

 

Results: Data filtering and in silico prediction tools identified a damaging and disease-causing single base mutation in X-chromosome gene MSN (c.511C>T p.Arg171Trp), not identified previously in gene variant databases. The mutation was validated in all family members by Sanger sequencing, confirming the proband was hemizygous X-linked recessive (-/T) and had inherited the affected T allele from his non-symptomatic carrier mother (C/T). Western blot has demonstrated the absence of moesin (MSN) protein in proband lymphocytes, compared with normal expression in lymphocytes from the healthy control, father and mother. qPCR identified significantly lower levels of MSN mRNA transcript expression in the proband compared to the healthy control in whole blood (P = 0.02) and in lymphocytes (P = 0.01). These results confirmed MSN deficiency in the proband, directly causative of his immunodeficient phenotype.

 

Expected results: We expect that proband primary lymphocytes transfected with custom designed guide RNAs, wild type donor sequence and Cas9 v2 protein, will undergo homology directed repair of the R171WMSN mutation with limited off-target effects, with rescue phenotype confirmed by qPCR/Western Blot.

 

Biography

Ewelina Kawecka is pursuing her PhD (2nd year) studies. Her Bachelors’ thesis, at Cardinal Stefan WyszyÅ„ski University in Warsaw, was a typical review dedicated to acute myeloid leukemia. The research during Master studies was carried out at Warsaw University of Life Sciences (WULS-SGGW). The Master’s thesis was focused on the mechanisms of the coat colour genes inheritance in coloured mice. Currently, her PhD studies are held in two places. The experimental part of the studies is conducted at the Institute of Genetics and Animal Breeding Polish Academy of Sciences, near Warsaw, but studies and lectures are performed on WULS, Veterinary Medicine Faculty. During her research, she is especially interested in Understanding of Complexity of Interaction between Phenotype and Genotype of Domestic Animals. 
 

Abstract

Inflammatory state of the mammary gland (mastitis) is mainly caused by bacteria. Mastitis is characterized by physical, chemical and microbiological changes in the milk composition. Both clinical and subclinical mastitis causes economic losses. Commonly two groups of staphylococci, important agents of mastitis, are distinguished: coagulase-positive (CoPS) and coagulase-negative (CoNS). CoPS cause predominantly chronic subclinical mastitis while CoNS are considered as minor pathogens causing mild clinical disease. The study was performed to measure differences in the level of expression of genes CXCL5, ITGAL and CCR1 in udder secretion tissue taken from cattle infected with CoPS and CoNS and from healthy animals. The study was conducted on 40 Polish Holstein-Friesian cows of Black-and-White variety. The animals were suffering from chronic and recurrent mastitis. Altogether, 51 parenchyma samples from udder quarters were collected: CoPS-infected (N=25), CoNS-infected (N=13) and non-infected (N=13). Total RNA was isolated using RNeasy Mini Kit (Qiagen), then cDNA templates were prepared and gene expression was determined using qPCR (LightCycler 480, Roche). The GAPDH gene was used as a reference. The expression level of the CXCL5 gene was higher in samples of animals infected with CoPS and CoNS than in non-infected ones. There were differences in the ITGAL gene expression between all three studied groups: higher mRNA level was in the CoPS-infected than in the CoNS-infected samples, and higher mRNA levels in the CoPS-infected and CoNS-infected samples than in non-infected ones. However, no differences in the expression of the CCR1 gene between studied groups were observed. Increased expression of studied genes in both CoPS-infected and CoNS-infected animals proves that CoNS also trigger the immunity of udder secretory tissue, although, they are considered as less pathogenic bacteria.