Day 15 :
- Genomics | Next Generation Sequencing | Cancer Biology | Bio-Engineering | Biomarkers Structural Biology | Integrative Biology
Location: Orly
Chair
Laila Alves Nahum
René Rachou Institute, Brazil
Co-Chair
Mamoru Shoji
Emory University School of Medicine, USA
Session Introduction
Nehir Ozdemir Ozgenturk
Yildiz Technical University, Turkey
Title: Pathways and co-expression network analysis of immune-related genes in shortterm calorie restricted mice
Biography:
Abstract:
Mamoru Shoji
Emory University School of Medicine, USA
Title: Inhibition of breast cancer bone metastasis and pancreatic and colon cancer by synthetic curcumin analogue UBS109
Biography:
Mamoru Shojiobtained his Medical Degree from the Hokkaido University, Japan, and completed internships at the US Naval Hospital, Yokosuka, Japan and the University of Pennsylvania in Philadelphia. He did his residency in Internal Medicine at the Lahey Clinic, Boston and fellowship training in Immunology at the Peter Bent Brigham and Robert Breck Brigham Hospitals (mentor, John R David, MD), Harvard Medical School in Boston, in Tumor Immunology at the University of Minnesota (mentor, Charles F Mckhann, MD from Massachusetts General Hospital) in Minneapolis, followed by fellowship in Hematology and Medical Oncology at Emory University (mentor, Charles M Huguley, Jr., MD).
Abstract:
Biography:
Marta Koblowska is currently the Director of the Laboratory of Bioinformatics and Systems Biology at the Faculty of Biology, University of Warsaw. Since 2008, she is the Head of the Laboratory of Microarray Analysis, in the Institute of Biochemistry and Biophysics, Polish Academy of Sciences. Her main research interests focus around chromatin function in regulating gene expression changes in plant adaptation to stress conditions. Her group recently showed that plant specifi c histone deacetylase HD2C interacts with BRM-containing SWI/SNF chromatin remodeling complex and both are involved in mediating the heat stress response in Arabidopsis.
Abstract:
One of the major abiotic constrains aff ecting plant growth is soil salinity. Despite many years of studying the molecular basis of plant response to high salinity, we still have gaps in our understanding of complex mechanisms underlying plant tolerance to salinity. To advance our knowledge about the early stages of plant cell response to salinity, we carried out a timeseries experiment during the fi rst 100 minutes of high-salt stress. As the most suitable model for performed studies, we chose Arabidopsis T87 cell line, off ering a relative cellular homogeneity comparing to a mixture of cells building the whole seedling or their organs. Our previous results describing nucleosomal response to high salinity, cold and abscisic acid (ABA) showed that Arabidopsis T87 cell line is a very convenient model to analyze stress response at the cellular level. To establish if frequent passages had an impact on T87 cells genome, we characterized a genetic variation in T87 cells. Apart from our previous data demonstrating that phosphorylation of histone H3 (H3S10ph) is a nucleosomal marker of cells standard behavior under stress, we also showed a novel histone modifi cation, H4K16ac to be a valid epigenetic signature of plant stress response. Transcription profi ling of T87 cells led to identifi cation of previously unrecognized genes, strongly activated during fi rst few minutes of salinity stress. Time-series transcriptome analysis during salinity stress followed by Bayesian network modelling recognized a set of hub genes directing the early response of plant cells to salinity stress.
Michael Bergel
Texas Woman’s University, USA
Title: Regulation of mitotic spindle polymerization by a novel histone deacetylase 3-linker histone H1.3 protein complex
Biography:
Michael Bergel is currently an Associate Professor at Texas Woman’s University (TWU), the largest university primarily for women in the United States. His lab has recently submitted a provisional patent application: U S Provisional Patent Application No. 62/567,089 entitled “Use of histone acetyltransferase inhibitor amidoximes as anti-proliferative agents”, fi led October 2, 2017. During his Postdoctoral training at the NIH, NCI with Dr. M Bustin, he specialized in the fi eld of chromatin. Specifi cally, he studied the HMGN1/2 proteins and their acetylation by the histone acetyltransferases p300 and PCAF. He also demonstrated that HMGNs are involved in regulation of core histone posttranslational modifi cations. He obtained his Master’s and PhD from the Hebrew University of Jerusalem in the fi eld of Cancer Biology, mentored by Dr. Jacob Hochman. His research interest includes chromatin, cancer biology, DNA repair and cellular UV response.
Abstract:
Histone deacetylase 3 (HDAC3) and linker histone H1 are involved in both chromatin compaction and the regulation of mitotic progression. However, the mechanisms by which HDAC3 and H1 regulate mitosis as well as the factors controlling HDAC3 and H1 activity during mitosis are unclear. Furthermore, as of now, no other association between class I, II or IV HDACs and linker histones has been reported. Here, we describe a novel HDAC3-H1.3 complex containing SMRT and N-CoR and at least four other proteins which accumulated in synchronized HeLa cells in late G2 and mitosis. Nonetheless, the deacetylation activity by the HDAC3 in the complex was evident only in mitotic complexes. HDAC3 associated to H1.3 was highly phosphorylated on S424 only during mitosis. Isolation of inactive HDAC3-H1.3 complexes from late-G2 cells and phosphorylation of HDAC3 in the complexes at serine 424 by protein kinase CK2 (also known as casein kinase 2), activated the HDAC3 in vitro. In vivo, CK2a and CK2a’ double knockdown cells demonstrated a signifi cant decrease in HDAC3 S424 phosphorylation during mitosis. HDAC3 and H1.3 co-localized in between the chromosomes with polar microtubules and spindle poles during metaphase through telophase and partially co-localized with chromatin during prophase and interphase. H1 was previously reported to associate with microtubules; thus, it could potentially function in targeting HDAC3 to the microtubules. We recently demonstrated that HDAC3, H1.3 or double knockdown cells have a lower microtubule polymerization rate in mitotic cells, thus supporting the role of the activated HDAC3-H1.3 complex in regulating mitotic microtubule growth.
Witold Chmielewski
Dentistry of Laval University, Canada
Title: Engineering human oral mucosa for clinical application
Biography:
Abstract:
Soft tissues such as skin and oral mucosa defi cits are usually corrected with autologous tissue collected from diff erent donor sites. Considered as the gold standard in damaged tissue reconstruction, this procedure is hampered by signifi cant limitations that include the limited amount of tissue to be collected, the creation of new fragile sites and the possible inappropriate healing of those donor sites. To overcome these limitations, some clinical initiatives have shown the possible use of engineered soft tissues such as oral mucosa for tissue reconstruction. Th us, our primary goal was to optimize the needed conditions for engineering clinically useful gingival human tissue. To reach our goal, we used primary human epithelial cells and fi broblasts that have been isolated from small gingival biopsies. Cells were propagated and then used to engineer human oral mucosa using a collagen scaff old. Before graft ing, tissue structure and protein production were investigated using histological and immunohistochemical techniques. Th e in vivo studies were performed by graft ing the engineered tissue onto the dorsa of immunodefi cient mice. Aft er 15 and 60 days post graft ing, biopsies were collected and used to evaluate the structure of the newly generated mucosa. Interestingly, our data demonstrated that isolated gingival cells were able to adhere and proliferate when seeded into collagen scaff old. Epithelial cells gave a well-structured and stratifi ed epithelium, basically being cultured into a connective tissue (collagen matrix populated with gingival fi broblasts). Following graft ing, the engineered human oral mucosa was able to generate mucosa that covers all available graft ing surfaces. Th e tissue contained a well-vascularised lamina propria and well-structured epithelium. Both structures communicate through a basement membrane containing lamini-5 and type IV collagen. All together, the results demonstrate the usefulness of engineered oral mucosa tissue as an alternative to replace damaged gingiva.
Alexander Archakov
Institute of Biomedical Chemistry, Russia
Title: Molar concentration welcomes avogadro in postgenomic analysys
Biography:
A I Archakov is a Full Member of the Russian Academy of Sciences and Professor & Scientifi c Advisor at Institute of Biomedical Chemistry. He has organized scientifi c school to study molecular organization and functioning of oxygenase cytochrome P450-containing systems, molecular mechanisms of the structure and function of membranes and biological oxidation. He has guided the institute’s members in developing a fundamentally new pharmaceutical composition “Phosphogliv” with antiviral activity for the treatment of liver diseases of various etiology. He is the pioneer in the development of proteomics in Russia. Currently, he is the International “Human Proteome” Project Coordinator in Russia. He is one of the Russia’s top 100 scientists with Hirsch number 27. He is the author of more than 700 scientifi c works including about 482 scientifi c articles, 6 monographs, 30 patents and author’s certifi cates. He was Scientifi c Advisor for 15 Doctors’ and more than 60 PhD theses. He is the winner of three state prizes of the USSR, the RSFSR and of the Russian Federation.
Abstract:
Alex Chenchik
Cellecta, Inc., USA
Title: Targeted single-cell RNA expression profi ling for biomarker discovery
Biography:
Alex Chenchik is the President and Scientifi c Director of Cellecta Inc., Mountain View, California, USA. His work focuses on “Development and application of next generation functional genomic technologies for discovery biomarkers, drug targets and development novel drugs”. He worked for Systems Biosciences, LLC as Vice- President of R/D and developed genetic screen technology with pooled lentiviral shRNA libraries in combination with a wide range of reporter cell lines. He also worked for BDB Clontech as Director of GCA Department and participated in the development of microarrays and disease-profi ling arrays for expression profi ling, PCR-based technologies for gene cloning, and subtraction-based approach for discovery of differentially expressed genes. He has done PhD in Molecular Biology (1982) from Institute of Molecular Biology, Moscow, Russia. He did MS in Chemistry (1978) at Institute of Fine Chemical Technology, Moscow, Russia.
Abstract:
Arieh Zaritsky
Ben-Gurion University of the Negev, Israel
Title: Multiplication of virulent bacteriophage: Interactions with the host
Biography:
Arieh Zaritsky obtained a distinguished MSc in Genetics at the Hebrew University, Israel in 1967. He completed his PhD from Leicester University, UK in 1971 and Post-doctorate at University Institute of Microbiology, Copenhagen, Denmark in 1972. During his career, he has instructed over 50 graduate students/scientists and was awarded numerous research grants. He visited higher education institutions around the world and delivered invited lectures at international meetings. He is a recognized expert in Bacterial and Bacteriophage Physiology, on which he has published about half of his 130 peer-reviewed articles, and was awarded (1994) Burroughs-Wellcome/ ASM Visiting Professorship.
Abstract:
Dependence of virulent (bacterio) phage multiplication on the physiological state of its host, conceived in the 1940’s,was refi nedfor the T4/Escherichia coli model system.Th e knownkinetic parameters (adsorption rate, eclipse and latent periods, ripening-rate, and consequent burst size) are relatedsolely to the host’s physiological state expressed by the bacterial growth rate before infection.Numerical models were advanced to explain (a)dependence of phage multiplication dynamics on host’s physiology, (b) co-existence of phage and its susceptible bacteria based on phage suicideand (c) kinetics of cell lysis based on materials corrosion, statistics of extremes and updated knowledge on bacterial physiology and phage biology. A mathematical model (d) was devisedto maximize phage titers by adjusting values of bacterial doubling time and initial multiplicity of infection (MOI). Results display a range of possible values along a golden strip in the relevant plane, and times to achieve these maxima and gains were evaluated.Resolution of the adsorption kinetics was refi ned (e) by frequent (~5 min-1) sampling at MOI=1 during the fi rst 6 min. Th e observed fast drop in free phage and bacteria is consistent with a relatively simple model. Th e sharper reduction in viable cells indicates that adsorption is more complex than thought to be.Th e consistencies of the various models with existing experimental resultssupport predictability and potential use to improve phage therapy.
JoonChing Juana
University of Malaya, Malaysia
Title: Biological and chemical fi xation of carbon dioxide
Biography:
Joon Ching Juan received his BSc in 2003 and PhD in 2007 from National University of Malaysia, Malaysia. Currently, he is an Associate Professor of Catalysis at Nanotechnology and Catalysis Research Centre, University of Malaya, Malaysia and also Senior Research Fellow (Adjunct) position at Monash University, Sunway Campus. Until now, he has managed to publish more than 100 publications, co-author four book chapters and his H-index is 20 (2017). He is the recipient of several awards including, Malaysia’s Research Star Award (2017) and National Young Scientist Award (2016).
Abstract:
- Human Genomics | Bioinformatics in Genomics | Micro RNA | | Biophysics | Cell biology
Location: Orly
Chair
Michael Bergel
Texas Woman’s University, USA
Co-Chair
Marta Koblowska
University of Warsaw, Poland
Session Introduction
Manjit Kaur
National Human Genome Research Institute - NIH, USA
Title: International Summit in Human Genetics and Genomics (ISHGG): Training the next generation of scientists and clinicians in human genetics and genomics in developing or genetics resource poor countries
Biography:
Manjit Kaur completed her MS (Microbiology) from University of Maryland, USA; an MBA from Johns Hopkins Carey Business School, Baltimore, Maryland, USA. She is an Interdisciplinary Scientist trained in microbiology, clinical pathology, infectious diseases, recombinant vaccines (cholera and malaria), biotechnology and human genetics and genomics. She previously worked for Academia, the Department of Defense and the private sector, before arriving at National Institute of Health, USA (2001), to work on neural tube defects. She now manages International Program at NHGRI that helps fi ll the knowledge gap in genetics and genomics in developing/genetics resource poor countries.
Abstract:
Genomics is increasingly becoming the backbone of all biomedical research and clinical application. Inherited and de novo disorders are adding to the burden of disease and disability in developing countries and straining their resources. Advances in human genetics and genomic research now make it possible to prevent, diagnose and treat many genetic and congenital birth defects; and proven strategies help manage unanticipated conditions. Unfortunately, many countries lack trained geneticists and the subject is not included in their curriculum, thus making it diffi cult to address these issues. To help fi ll the knowledge gap, National Human Genome Research Institute (NHGRI) developed ISHGG, a 5-year initiative (2016-2020), to assist developing countries build capacity in genetics and genomics. In 2016 and 2017, NHGRI sponsored professionals (n=19, n=26), from multiple health-allied disciplines, from several countries (n=13, n=24). Th e summit included didactics, clinics, fi eld trips, workshops and a patient-panel. Pre- and post-surveys conducted helped gauge knowledge about the subject, interest and learning among people. Th e results indicated that the summit was a unique learning opportunity for participants and speakers, and its continuance was encouraged. One-year outcomes from the 2016 summit included collaborations (27), publications (54) and grants (24). Annual feedback from participants on their eff orts in genetics/genomics, indicates that the summit is making good progress in achieving its goals of promoting genetic and genomic research and medicine through international cooperation and collaboration; identifying and fi lling the knowledge gap in genetics and its related technologies in developing countries and help reduce the burden of disease and disability in these countries.
Biography:
Abstract:
As scientifi c technology continues to improve, so does the ability of shared resource labs to eff ectively serve their scientifi c partners. However, an increase in laboratory customers presents a unique set of issues, which can hinder a lab’s operational effi ciency and impact overall results. In this workshop we will identify opportunities for optimized lab operations effi ciency, discuss details of an eff ective laboratory operations strategy, and provide insights on best practices and current tools in the industry. Investing time and thought into refi ning your laboratory operations will pave the way for satisfi ed partners and improved innovation.
Ana Fernández Marmiesse
University Hospital of Santiago de Compostela, Spain
Title: Neuromegen: Achieving rapid diagnosis for neurodevelopmental disorders
Biography:
Abstract:
Sarah S. Knox
West Virginia University School of Public Health, USA
Title: Wave/particle duality in biomedical research
Biography:
Abstract:
Igors Pupko
Reproductive Medicine and Genetic Clinic iVF Riga, Latvia
Title: Diffi culties of mosaicism interpretation in embryo aneuploidy screening in IVF setting
Biography:
Abstract:
Embryo aneuploidy screening (PGT-A) using diff erent approaches (FISH, arrayCGH, NGS) has been widely used in IVF setting worldwide. Chromosomal aberrations found in embryos could be as high as 50% from all embryos. Mosaic chromosomal aberrations oft en seen in embryos are well described. Diffi culties in interpreting results are challenging especially when there are no euploid embryos suitable for transfer. Several guidelines are available and they all state that euploid embryo should be preferred over aneuploid or mosaic aneuploid embryo. In case of mosaic embryos, chromosomal aberrations including chromosomes 13, 18, 21, as well as chromosomes which are linked with uniparental disomy, should be excluded. Embryo selfrescue is known mechanism, which in most cases manages to remove cells with aneuploidy and continue development from mosaic aneuploid embryo to child with normal karyotype in up to 80% pregnancies. Th e experience of our clinic has allowed to accumulate knowledge about the mosaic aneuploid embryo PGT-A data interpretation. Data interpretation should be done by specialists – geneticists and molecular geneticists to avoid misdiagnosis and carefully consider possible eff ects of mosaic aneuploidy, especially if there are no euploid embryos for transfer. In practice we have seen several possible outcomes aft er embryo self-rescue – normal and ongoing pregnancy, miscarriage and uniparental disomy..
Miriam Payá Milans
University of Tennessee, USA
Title: Exploring the design of RNA-Seq analysis pipeline
Biography:
Miriam Payá Milans is a Young Researcher with an international background. On her PhD studies, in Seville Spain, she worked on the molecular and biochemical analysis of genes in the lipid biosynthesis pathway. Part of that research was carried out in collaboration with laboratories at the Universities of Missouri and Guelph. After PhD, she decided to expand into the fi eld of bioinformatics, with her fi rst work done on SNP analysis in octoploid strawberry, in Barcelona. She is currently working as Postdoctoral Fellow at University of Tennessee, focusing on the analysis of RNA-Seq data in several plant species. There, she helps teaching at RNASeq analysis workshops and offers bioinformatics support to colleagues.
Abstract:
Transcriptome analysis through RNA-Seq data is well-established in model organisms, but the data analysis on other species can be less straightforward. Compared to other kingdoms, genome sequencing projects are far lower in plants, resulting in an increased challenge to the study of crop species. For example, in working with blueberries, we have more than one species of interest, fewer genomic resources than many model plant systems and various levels of polyploidy. When developing a workfl ow of soft ware tools to analyze this data, a researcher faces decisions among numerous algorithms at each step. We have explored some of the current options available to analyze RNA-Seq data in two situations: fi rst, when the closest reference genome is from a diff erent species and second, when a polyploid species is being sequenced but the closest reference genome is a diploid progenitor species. Results are compared between the usages of a related species reference genome against the utilization of de novo transcriptome assemblies. Further, comparisons are made amongst read correcting, quality trimming, and read mapping soft ware choices. We conclude that diff erent soft ware packages and approaches infl uence RNA-Seq analysis and recommend the election of parameters that maximize desired metrics when using polyploid species and/or a distant reference genome.