Day 2 :
- Track 4: Cell Biology, Track 5: Tissue Biology, Track 6: Developmental Biology
Location: Valencia B, Melia Valencia
Chair
Anja Nohe
University of Delaware, USA
Co-Chair
Nirmal K. Shetty
Shri Krishna Research Centre, India
Session Introduction
Anja Nohe
University of Delaware, USA
Title: Identifying new targets to improve skeletal formation in human
Time : 09:00-09:20
Biography:
Anja Nohe is an associate professor in the Department of Biological Sciences at the University of Delaware. She 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. She is a member of several editorial boards and her research is currently funded by the National Institute of Health. 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:
Humans rely on their skeleton during their lifespan for several crucial functions as diverse as body support, walking, and energy balance. Unfortunately, during aging the human skeleton loses bone mass and its function is impaired. This leads to diseases such as Osteoporosis. A woman’s risk of breaking a hip due to osteoporosis is equal to her risk of breast, ovarian and uterine cancer combined. And a man age 50 or older is more likely to break a bone due to osteoporosis than he is to get prostate cancer. For most bone diseases, new innovative treatments and therapeutics are needed. However, in order to develop these the formation of the skeleton and the skeletal changes in adults must be determined. Bone is a dynamic living tissue that hosts a variety of different cell types embedded into mineralized matrix. Bone morphogemetic protein 2 (BMP2) is a growth factor that drives stem cell differentiation and bone growth in vivo. However, it has several side effects, when being used in the clinic. Therefore therapeutics and treatments based on the signaling pathway of BMP2 may show great potential to induce skeletal growth. Using a systems biology approach we modeled the BMP2 signaling pathway and defined key targets in the BMP2 signaling pathway. We confirmed their role using atomic force microscopy combined with fluorescent microscopy. Moreover, we developed a peptide that activates specific signaling pathway in vitro and in vivo. We showed that systemic injection of this peptide in mice causes increase in bone mineral density and mineral apposition rate as well as trabecular thickness. These results suggest that the peptide is a powerful mediator of skeletal growth and may be used to improve skeletal formation in adults.
Imre Olah
Semmelweis University, Hungary
Title: Organization of avian thymic medulla and surfactant production
Time : 09:20-09:40
Biography:
Imre Olah has completed his MD at age of 24 from Semmelweis University Faculty of Medicine. His PhD and DSc were completed from Hungarian Academy of Sciences. His postdoctoral studies were made at the Anatomy, Histology and Embryology Department, Semmelweis University. He worked as Research Associate in Department of Biological Structure, Washington State University Seattle, Poultry Science Department Mississippi State University, and Clemson University South Carolina. He was professor and Head of Department of Human Morphology and Developmental Biology, Semmelweis University. He has published more than 130 papers, and book chapters. Recently professor emeritus
Abstract:
Thymic medulla of the chicken is compartmentalized to 1.) keratin positive network (KPN), and 2.) keratin negative areas (KNA). KPN is connected with the cortical epithelial reticular cells (ERC) and the KNA is a dilation of the interlobular septae consisting of reticular connctive tissue. “Derailed” differentiation or development of thymic ERC results in thymic cyst and/or Hassall’s body’s formation. Both cysts and Hassall’s bodies locate in the KPN of thymic medulla. Possibly, the differentiation of the cells of the thymic cyst and Hassall’s body‘s cells stopped in the early and late stages of development, respectively. The thymic ERC and the surfactant producing type II pneumocytes of the lung develop from the foregut endoderm. The transmission electron microscope shows, that the cells of the multicellular cysts are polarized and the structure of the cytoplasmic granules identical with that of the type II pneumocytes. At the apical side of the cyst epithelial cells express alpha smooth muscle actin. The lumen of the cysts is filled with a substance of medium electron density and strongly stained with anti-surfactant SP-B. These findings indicate, that the cyst epithelium actively secretes surfactant, which contribute to the central tolerance of thymus, and innate immunity. The thymic ERC and the surfactant producing epithelial cells of the cysts express MHC class II antigen unlike the type II pneumocytes.
Jamila Chakir
Laval University, Canada
Title: Regulatory role of microRNA in severe asthma
Time : 09:40-10:00
Biography:
Jamila Chakir is a full professor, department of Medicine at Laval University and Institut Universitaire de Cardiologieet Pneumologie de Québec. She obtained a PhD degree in Immunology in France. She received postdoctoral research training at Laval University and McGill University, Canada in inflammation and remodeling in asthma. Dr Chakir’s research focuses on cellular and molecular mechanisms of airway remodeling. 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 amember of different national and international scientific committees and has received several awards from national and international organisations.
Abstract:
Allergic asthma is a chronic inflammatory disease characterized by an airway hyper-responsiveness and a deregulated inflammation in response to allergens. Available treatments are mainly symptoms-driven and do not interfere with the natural history of the diseases. Severe asthma constitutes a challenging problem for the healthcare system. Its heterogeneity complicates the management of the disease. There is a significant need to understand the pathogenesis of severe asthma. Bronchial epithelium is considered a key player in coordinating airway wall remodelling. While, in mild asthma, the epithelium is damaged and fails to proliferate and to repair in severe asthma the epithelium was reported to be highly proliferative and thicker. This may be due to different regulatory mechanisms. We studied microRNAs profile and evaluated their role in regulating proliferation of bronchial epithelial cells obtained from severe asthmatic subjects in comparison to cells obtained from mild asthmatics and healthy controls. We found that in mild asthmaepithelial cells produce high amount of TGFï¢1 and express high level of TGFï¢-RI and phosphorylated-Smad3, indicating that TGFï¢1signallingis up-regulated. In severe asthma, this pathway was down-regulated. Thus, in epithelial cells from severe asthmatics compared to mild asthma and controls, miR-19a, a member of the miR-17~92 cluster, is up-regulated and increases proliferation. Knockdown of miR-19a in epithelial cells reduces significantly their proliferation through targeting TGF-ï¢ downstream signaling. Our study uncovers a new regulatory pathway involving miR-19a that is critical to the severe phenotype of asthma and indicates that down-regulating miR-19a expression could be explored as a potential new therapy to modulate the epithelium repair in asthma (Funded by the CIHR).
Helena Barreto Henriksson
Sahlgrenska University Hospital, Sweden
Title: Stem cell biology and applications in preclinical experiments
Time : 10:00-10:20
Biography:
Helena Barreto Henriksson is active in the regenerative medicine research field since 10 years with main focus on molecular regenerative features of cartilage. Currently, Helena is working as a researcher at the Dept. of Orthopaedics, Sahlgrenska University hospital/Gothenburg University, Sweden in the translational medicine field; “from preclinical to new clinical approaches” e.g. stem cell therapy for degenerated intervertebral discs as well as studying local tissue specific stem cell populations in the disc. Helena Barreto Henriksson finished her PhD studies (Medical Science) at Gothenburg University, 2010 with the thesis “Intervertebral disc regeneration, Studies on stem cell niches and cell transplantation.
Abstract:
Regenerative medicine is a rapidly increasing research field worldwide. In this field, cell therapy applications involving mesenchymal stem cells(MSCs) are currently under investigation, some applications are already in clinical use. Cell sources for clinical treatments in clinical use are e.g. bone marrow derived MSCs. Low back pain is common in the Western world and intervertebral disc(IVD) degeneration is considered to be a major cause.Recently, stem cell therapy has been discussed as alternative treatment option for degenerated IVDs where the purpose would be to repair, maintain, or enhance the function of particular cell typesin the IVD.Further, normal cell proliferation and regeneration in the IVD are at present sparsely investigated. Cartilage is considered to lack/have a poor capacity of self-repair. However, studies have identified progenitor-/stem cells in cartilage(different mammalian species)and data point in direction that adult IVDs have a regeneration capacity, however slow.The possibility to stimulate local cells in situ would be an interesting biological treatment option. Preclinical experiments e.g. xenotransplantation animal models are useful for evaluation of e.g. the local microenvironment effects that MSCs will encounter after transplantation. We have investigated cellular migration and tissue distribution of transplanted MSCs bynon-toxic pre-labeling e.g. iron compoundsfor tracing in vivo as well as monitoring effects of different biomaterials e.g. cellular motilityon aligned collagen fibres coated surfaces (time-lapse methods). In conclusion, stem cell therapy using MSCs and/or to stimulate local stem-/progenitor cells hold a high promise for development of biological treatment options for degenerated cartilaginous tissues.
Bernardo L Trigatti
McMaster University. Canada
Title: High density lipoprotein signaling in macrophages and its role in atherosclerosis protection.
Time : 10:35-10:55
Biography:
Bernardo L Trigatti has completed his PhD in 1995 at McMaster University and postdoctoral studies from the Massachusetts Institute of Technology before re-joining McMaster University’s Department of Biochemistry and Biomedical Sciences in 2000. He is an Associate Professor at McMaster University and joined the newly formed Thrombosis and Atherosclerosis Research Institute in 2010. He is leading a lab group focusing on uncovering molecular pathways involved in the development of atherosclerosis and associated cardiovascular disease.
Abstract:
Macrophages play key roles in the development of atherosclerosis, a leading cause of coronary heart disease, stroke and peripheral vascular disease. Macrophages participate in all stages of atherosclerotic plaque formation. Lipid laden macrophages accumulate in developing atherosclerotic plaques. Macrophage apoptosis contributes to the development of lipid rich, cell free necrotic cores within atherosclerotic plaques, a key feature of the so-called vulnerable plaque. Vulnerable plaques with large, unstable necrotic cores are prone to rupture, resulting in occlusive and potentially devastating athero-thrombosis. High density lipoproteins (HDL) protect against the development, contribute to the stabilization and also trigger the regression of pre-established atherosclerotic plaques. Recent studies have revealed that HDL, in addition to its well established role in mediating cholesterol removal from atherosclerotic plaques, can also act as a signaling molecule in a variety of cell types. Our studies have explored the ability of HDL to trigger signaling events in macrophages activating pro-survival and migratory responses. These contribute to the protection of macrophages against apoptosis in atherosclerotic plaques, limiting the formation of necrotic cores, as well as the stimulation of macrophage egress from plaques, promoting the regression of pre-established atherosclerotic plaques. Identification of the signaling pathways involved in these processes will allow us to identify new therapeutic targets for plaque stabilization and to induce atherosclerotic plaque regression.
Nirmal K. Shetty
Shri Krishna Research Centre, India
Title: New nomenclature for pedigree charts based on the novel pattern of inheritance of ancestral and parental chromosomes
Time : 10:55-11:15
Biography:
Nirmal K Shetty is the Director of Shri Krishna Research Centre, Mumbai, India. He graduated from Madras Medical College, India, and studied Acupuncture in Shanghai, China. He is also a Consulting Acupuncturist for over two decades, and is associated with Cumballa Hill Hospital, Inlaks General Hospital and Shanti Avedna Cancer Hospice. His study focuses on innovative theoretical research at the interface, with the objective of giving a new perspective to inheritance of chromosomes. The study hopes to open new fields of research in future that may help in finding solutions to some genetic disorders and cancer.
Abstract:
A new nomenclature for pedigree charts was developed based on a fundamental new hypothesis which depicts a novel pattern of inheritance of ancestral and parental chromosomes. It gives a new dimension to the inheritance of hereditary traits. Of the two sex chromosomes XX or XY, the first chromosome ‘X’ represents ancestral and the second chromosome X or Y represents parental viz., mother or father respectively, autosomes are also differentiated in the same manner. In the pedigree charts, suffix numbers are given in sequential order to ancestral sex chromosomes and parental sex chromosomes separately depicting married partners as well. Applying the new nomenclature for pedigree charts gives better clarity with regard to inheritance of hereditary characteristics. This could help in genetic counseling and in understanding better, how some types of consanguineous marriages predispose their offspring to genetic disorders and that one type of consanguineous marriage does not affect the offspring. The new hypothesis is based on innovative theoretical research at the interface. Principle of opposites, Barr body, gene recombination during chiasma and natural selection, all play an important role in pre-determining the pattern of inheritance of chromosomes at the time of fertilization leading to the formation of the zygote. This hypothesis opens new fields for research in biology and genetics and may help future research in finding cures for some genetic disorders and cancer.
Jim Karagiannis
University of Western Ontario, United Kingdom
Title: On the computational ability of the RNA polymerase II carboxy terminal domain
Time : 11:15-11:35
Biography:
Jim Karagiannis is an associate professor at the University of Western Ontario in London, Ontario, Canada. His research makes use of the model eukaryote Schizosaccharomyces pombe and explores the complex post-translational modifications that take place on the carboxy-terminal domain (CTD) of the largest subunit of RNA polymerase II. Through an empirical examination of the informational properties and regulatory potential of the CTD, Dr. Karagiannis hopes to decipher the “programming language” used by eukaryotes to control aspects of gene expression.
Abstract:
The RNA polymerase II carboxy terminal domain has long been known to play an important role in the control of eukaryotic transcription. This role is mediated, at least in part, through complex post-translational modifications that take place on specific residues within the heptad repeats of the domain. In this report, the phenotypic effects of systematic site-directed mutations in the fission yeast RNA pol II carboxy terminal domain (CTD) are investigated. Remarkably, we find that alterations in CTD structure and/or phosphorylation result in distinct phenotypic changes related to morphogenetic control. A hypothesis based upon the concepts of “informational entropy” and “algorithmic transformation” is developed to explicate/rationalize these results. In addition, a formal mathematical conceptualization of CTD modification (in the form of a semi-Thue string rewriting system) is presented. Since the semi-Thue formalism is known to be Turing complete, this raises the possibility that the CTD – in association with the regulatory pathways controlling its post-translational modification – functions as a biological incarnation of a universal computing machine. These ideas imply that the controlled manipulation of CTD effectors could be used to “program” the CTD and thus to manipulate biological processes in eukaryotes in a definable manner.
Yunfeng Zhou
Wuhan University, China
Title: Telomere/telomerase and radiosensitivity
Time : 11:35-11:55
Biography:
Yunfeng Zhou has completed his PhD/MD in 1991 from Lyon University, France. He is the Director of Hubei Cancer Clinical Study Center, Hubei Key Laboratory of Tumor Biological Behaviors and Hubei Radiotherapy quality control center. His main research fields including telomere/telomerase in anti-cancer therapy and radiation-guided gene therapy of cancer. In addition to being an outstanding oncologist, he was committed to Sino French medical exchange. Due to his great contributions, the French Government awarded him French Knight Badge (2006) and National Order of the Legion of Honour (2009). He published more than 100 papers in international and national journals.
Abstract:
Radiotherapy is the major method of malignant treatment and the high radioresistance of tumor cells is still the significant reason for the failure of radiotherapy. So identifying new factors that predict radioresistance is an area of intense research and could be of great value in the treatment of cancers. Based on our research during the past 15 years, we find that telomere, telomerase and telomere-binding proteins are important regulators of radiosensitivity. Firstly, our study indicated that telomere length may be used as a promising tool to predict the radiosensitivity of human carcinomas. Further, we found that telomerase and telomere-binding proteins (TPP1, POT1, TRF2 and CTC1) are effective radiosensitization targets in cancer radiotherapy. Moreover, our research team combine CArG element with hTERT promoter to form a new kind of chimeric promoter, which combines gene with ray skillfully and treat tumor with local therapy as well as inducing the expressing of therapeutic gene. Our research team has successfully construct a new kind of chimeric promoter system based on hTERT and verified its radiosensitization effect in cervical cancer, lung cancer and liver cell model. In summary, our research demonstrated that telomere, telomerase and telomere-binding proteins are effective radiosensitization targets in cancer radiotherapy. Now our research mainly focuses on their mechanisms of the radiation-sensitizing effect.
Hui Yang
Wuhan university, China
Title: Carboxyl terminus of Hsp70-interacting protein(CHIP) functions as a tumor suppressor and enhance the radiosensitivity in cervical cancer
Time : 11:55-12:15
Biography:
Hui Yang is a PhD candidate of Wuhan University, China. She took part in the group of Prof. Yunfeng Zhou who has been the head of Zhongnan Hospital of Wuhan University and research on the telomere/telomerase in anti-cancer therapy and radiation-guided gene therapy of cancer.
Abstract:
Cervical cancer recurrence and metastasis after radiotherapy is one of the main reasons lead to cervical cancer treatment failure. CHIP serves as a chaperone-associated Ubox-containing E3 ligase that can modulate a lot of tumor-related proteins and has been reported to act as an tumor suppressor in pancreative cancer, breast cancer, colorectal cancer and so on. But we know little about its roles in cervical cancer. In this study, we show a significant difference in the expression of CHIP between the normal squamous cervical epitheilia, high grade squamous intraepithelial lesions and invasive squamous cell carcinoma of the cervix tissues. Gene set enrichment analysis(GSEA) shows that the CHIP is related to cell cycle progression, cell apoptosis and DNA damage pathways. So we hypothesis that CHIP can modulate the radiosensitivity in cervical cancer. Here, we established two radioresisitant cervical cancer cell lines C33AR and HelaR by exposing their parental C33A and Hela cells to repeated X-ray irradiation with a total dose of 60Gy and 72Gy respectively. The radiosensitivity of these two pairs of radiosensitive and radioresistant cell lines were confirmed by clonogenic assays. We then examine the cell cycle distribution and cell apoptosis by flow cytometry and found that the radioresisitant cell lines prolonged G2 arrest and lesser apoptosis which compared to their parent cell lines after 6Gy X-ray irradiation. Furthermore, transwell, real-time PCR and TeloTAGGG telomerase PCR ELISA Kit were performed to examine cell invasion, telomere length and telomerase activity in these two pairs of cell lines separately and the C33AR and HelaR cell lines show a significant difference in cell invasion, telomere length and telomerase activity. In addition to this, real-time PCR and western blot were used to examine the expression of CHIP and hTERT respectively and show that the CHIP is low expressed in radioresistant cell lines, whearas the hTERT is high expression in radioresisitant cell lines. In order to further explore the relationship between CHIP, hTERT and radiosensitive, we use real-time PCR to detect the expression of CHIP and hTERT at different time points after 2Gy, 5Gy and 10Gy irradiations, the results show that the CHIP expression is accompany with the changing of hTERT, a few minutes after the high expression of hTERT, the CHIP is high expression and then the expression of hTERT is declined. Overexpression of CHIP in C33AR and HelaR cell lines show an enhancement of radiosensitivity and down regulate telomerase activity. These results showed that CHIP can be seen as a tumor suppressor and high expression of CHIP can enhance the radiosensitivity by negatively regulates telomerase activity. Hence, CHIP may served as a novel target radiosensitizer.
Ewa Maj
Polish Academy of Science, Poland
Title: Antiangiogenic treatment in non-small cell lung cancer (NSCLC)
Time : 12:15-12:35
Biography:
Ewa Maj is PhD student at Institute of Immunology and Experimental Therapy, PolishAcademy of Science. She has completed her M.Sc. of Biotechnology from University of Agriculture in Krakow and also M.Sc. of Medical Analytics from Jagiellonian University Medical College in Krakow. Before Ph.D. studies she worked in Laboratory of Autoimmunology in “Diagnostyka Medical Laboratories” as medical technologist.She has published about 9 papers as co-author in reputed journals and presented results of her research on a national and international conferences.
Abstract:
Lung cancer is the leading cause of cancer-related deaths worldwide. Due to lack of early symptoms patients are diagnosed with advanced stage of the disease. Growing tumors promotes angiogenesis inside malignant tissue, what next results in metastatic potential and poor prognosis. Tumor angiogenesis is one of the targets for anticancer therapy developed today. Malignant cells, including lung cancer cells, release many growth factors that are involved in tumor angiogenesis. Blocking signal transduction pathway of VEGF, main angiogenicfactor, by for example VEGF receptor inhibitors or anti-VEGF monoclonal antibodies results in endothelial cells apoptosis what in turn blocks angiogenesis. Recently it was discovered, that tumor suppressor p53 protein is involved in controlling tumor vascularization. In cancer tissue samples obtained from patients with lung cancer,immunohistochemical analysis showed that mutant p53 correlated with higher VEGF expression. In our study we decided to combine some tyrosine kinase inhibitors(TKI) with cytostatics: cisplatin and docetaxeland also calcitriol analog as a proposed treatment in non-small cell lung cancer (NSCLC) model. The research focused on combined effect of above mentioned drugs towards proliferation of lung cancer and endothelial cells and the VEGF production by cancer cells in vitro. The mechanism of observed downregulation of VEGF expression in lung cancer cells after exposure to combination of TKI with cytostatics was explored.
Justyna Trynda
Polish Academy of Science, Poland
Title: The role of microRNA-125b in calcitriol-induced differentiation of human leukemia and lymphoma cells
Time : 12:35-12:55
Biography:
Justyna Trynda is PhD student at Institute of Immunology and Experimental Therapy, Polish Academy of Science. She has completed her M.Sc. of Biology from University of Agriculture in Wroclaw and also Molecular Biology from Jagiellonian University in Krakow. Before Ph.D. studies she worked in Laboratory of Electron Microscopy in University of Agriculture in Wroclaw as senior technician. She has published about 2 papers as co-author in reputed journals and presented results of her research on a national conferences.
Abstract:
MicroRNAs are short (~22 nucleotides) single strands of RNA that function as regulators of mRNA translation. They have integral roles in a broad array of biological processes. Many microRNAs are implicated in the anticancer action of calcitriol (active form of vitamin D). One of the most important is miR-125b known as regulating vitamin D receptor (VDR) and vitamin D 24-hydroxylase- CYP24 expression. Moreover, miR-125bhave been reportedto be involved in a variety of cancers regulating cell cycle, differentiation and apoptosis by targeting a number of genes such as transcription factors, matrix-metalloproteases, members of Bcl-2 family, p53, NF-κB.The aim of our work was to study the role of miRNA-125b in anticancer activity of calcitriol in human leukemia and lymphoma cells. In our experiments we measured the expression of microRNA-125b after calcitriol treatment and correlated it with the level of mRNA and protein e.g. vitamin D receptor, vitamin D 24-hydroxylase- CYP24, membrane associated rapid response steroid receptor ERp57,and others, which are responsible for differentiation of cells. We conclude that microRNA-125b may regulates crucial molecules engaged in differentiation process of human leukemia and lymphoma cells after exposure to calcitriol.
Abdel-Hamid
National research centre, Egypt
Title: Diagnosis of dengue infection using metabolome analysis (biomarker profiles)
Time : 12:55-13:15
Biography:
Abdel-Hamid Zaki, Deputy of Pharmaceutical and Drug Industries Division (NRC). He was appointed as a head of Therapeutic Chemistry Department, National Research Centre, (2006, 2012)). He is working as professor of Applied Biochemistry at the same department. Major field of his interest is metabolomics in pharmaceutical research. He awarded many of scientific mission and grants from DANIDA (Denmark – 1994), TWAS (Italy-1997, 2001, 2003), FAPESP (Brazil, 2001),and UNESCO (2002). Abdel-Hamid was obtained and held PI for 5 international research projects from ISESCO- (1990-1993), TWAS- (1995-1996),TWAS ( 1998-1999), TWNSO- (2004-2006) and STDF (2014-2016).
Abstract:
Dengue is a major health and pressing threat to Malaysia with increasing atypical manifestations. In this study, metabolomics approach was used to identify metabolite candidates by means of 1H NMR- spectrometry as a diagnostic tool for dengue disease. The mid-stream urine collected from 52 patients diagnosed with dengue fever at Penang General Hospital and 43 healthy individuals was analyzed with 1H NMR spectroscopy, followed by chemometric multivariate analysis. NMR signals which highlighted in the OPLS-DA S-plot were selected and identified using Human Metabolome Database (HMDB) and Chenomx Profiler. A highly predictive model was constructed from urine profile of dengue infected patients versus healthy individuals with the total R2Y (cum) value is 0.935, and the total Q2Y (cum) value is 0.832. The differences between infected patients versus healthy individuals were found to be related to amino acid metabolism, tricarboxylic acid intermediates cycle and β-oxidation of fatty acids. Distinct variations in certain metabolites were recorded including amino acids, various organic acids, betaine, valerylglycine, myo-inositol and glycine. The results open up a possibility of rapid, non-invasive analysis and diagnosis of dengue disease using urine metabolic profile.
- Track 10: Systems Biology
Location: Valencia B, Melia Valencia
Chair
Robert A. Drewell
Clark University, USA
Co-Chair
Jacqueline M. Dresch
Clark University, USA
Session Introduction
Robert A. Drewell
Clark University, USA
Title: Decoding the regulatory architecture in Drosophila Hox gene enhancers
Time : 14:00-14:20
Biography:
Robert A. Drewell completed his PhD at Cambridge University in 1999 and conducted postdoctoral studies at University of California, Berkeley and California Institute of Technology. He is an Associate Professor at Clark University and has published more than 30 papers.
Abstract:
In Drosophila, the Abdominal-B homeotic (Hox) gene is expressed in a spatially and temporally restricted pattern along the anterio–posterior axis during embryonic development. The transcription pattern is controlled through specific interactions between transcription factors and a number of enhancers in the neighboring intergenic region. Using computational, mathematical modeling and experimental molecular genetic approaches we investigate how the architecture of transcription factor binding sites mediates the functional activity of these enhancers. A cross-species comparison of the enhancers reveals an evolutionarily conserved signature motif containing two FUSHI-TARAZU activator binding sites that appear to be acting in a cooperative manner. We also find that the transcriptional repressors KNIRPS, KRUPPEL and GIANT are able to restrict gene expression from the enhancers through different molecular mechanisms including short-range repression and competitive binding. Thermodynamic mathematical models can accurately predict the regulatory logic at the enhancers. Our results demonstrate that the transcriptional output of the enhancers relies on a complex set of combinatorial inputs mediated by specific transcription factor binding sites and that the sequence architecture at the enhancers is critical to maintain robust regulatory function.
Jacqueline M. Dresch
Clark University, USA
Title: Detecting nucleotide interdependency in transcription factor binding sites
Time : 14:20-14:40
Biography:
Jacqueline Dresch completed her PhD in Mathematics and Quantitative Biology in 2012 from Michigan State University and postdoctoral studies from Harvey Mudd College in 2013.She is currently an assistant professor in the Mathematics and Computer Science Department at Clark University. She leads an active interdisciplinary undergraduate research group and has published multiple collaborative papers in reputable journals.
Abstract:
A long-standing question in modern molecular biology is how an organism’s genome encodes the instructions for every biological process that takes place throughout their lifetime. In eukaryotes, much of the focus of this field has been on understanding gene expression during development and the binding of protein transcription factors (TFs) to DNA cis-regulatory modules (CRMs) to regulate this expression. Our research focuses on the model organism Drosophila melanogaster. We have explored nucleotide dependencies within binding sites for a group of transcription factors known to be critical to Drosophila development. Our results suggest that many of these proteins have varying levels of nucleotide interdependencies within their DNA recognition sequences, and that, in some cases, models that account for these dependencies greatly outperform traditional models used to predict binding sites.
Bin Zhang
Icahn School of Medicine at Mount Sinai, New York
Title: Comparative network analysis of insulin resistance in caucasian and african americans
Time : 14:40-15:00
Biography:
Bin Zhang is an associate professor of the Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, USA. He holds a Ph.D. and a master degree in Computer Science from the State University of New York at Buffalo, a master degree in electronic engineering from Tsinghua University, China, and a bachelor's degree in electrical engineering from Tongji University, China. His expertise lies in systems biology. He has published 86 peer-reviewed papers including 9 papers in Nature, Science, Cell, Nature Genetics, and PNAS. As of April 2015, his publications have been cited 7131 times.
Abstract:
African Americans (AA) have more pronounced insulin resistance and higher insulin secretion than European Americans (Caucasians or CA) matched on age, gender, and body mass index (BMI). However, molecular mechanisms underlying distinguished insulin resistance in AA remains unknown. In this study, we performed integrative network analysis the gene expression data from the subcutaneous adipose tissue of 99 CA and 37 AA metabolically characterized non-diabetic subjects with a range of insulin sensitivity (SI) and BMI values. We systematically identified the common and ethnicity-specific co-expressed gene modules and drivers. Many adipose co-expression modules were enriched for genes differentially expressed between the two ethnicities or with differential connectivity (MDC) among members of the network module. For example, SIis positive correlated with transcript modules enriched for mitochondrial metabolism in both groups. Several SI associated co-expressed modules are enriched for genes differentially expressed between groups, or had different modular connectivity among members of the network module. SI-associated transcriptional networks that were deranged predominantly in one ethnic group may explain the physiological features of glucose homeostasis among AA subjects. This study paves a way for systematically understanding the molecular mechanisms of insulin resistance in both CAs and AAs. Further studies will be required to identify how genetic and epigenetic factors determine the structure of co-expression networks in adipose tissue that modulate glucose-homeostasis and related physiological traits.
SÃlvia M. Rocha
Universidade de Aveiro, Portugal
Title: Constructing a workflow based on breath and urinary metabolomics to go further on asthma management
Time : 15:00-15:20
Biography:
Sílvia M. Rocha is assistant professor in the Chemistry Department at the Aveiro University. She is BA in Pharmaceutical Sciences at the Pharmacy Faculty (Coimbra University), and PhD in Chemistry (Aveiro University). For the last 22 years, she has performed studies on the characterization of plant-derived natural products, prospection of bioactive compounds, and metabolomics applied to human fluids, plants and microbial systems. Her main skills are oriented to sample preparation and high through-put analysis based on comprehensive two-dimensional gas chromatography and mass spectrometry developments. She published over 85 SCI papers, 2 books, 7 book chapters, and 3 patent applications.
Abstract:
Breath and urinary-based metabolomics are centered on the capture, analysis, and establishment of metabolite biomarker patterns in humans, towards the development of platforms that may be used as tools in a broad spectrum of medical problems. Current developments confirm the potential of this upward trend in the development of rapid, low-cost and non-invasive real-time disease diagnostic tools. Advancements in sampling methodologies and an explosion in the diversity, versatility, and sensitivity of associated detection platforms have catalyzed the interest on the body fluid metabolomics studies. For instance, multidimensional gas chromatography (GC×GC-ToFMS) allowed to go forward on breath and urinary metabolomics towards the understanding asthma perturbations in humans. Asthma is a heterogeneous inflammatory disorder, which is now one of the commonest chronic disorders in the world, and it is also associated with high direct and indirect health costs, especially related with diagnosis and treatment. A particular emphasis in the talk will be placed on the more recent developments on breath and urinary asthma metabolomics towards disease management (diagnosis, disease status evaluation, follow-up therapy and personalized disease evaluation). Challenges associated with metabolomic workflow construction, namely those related to the complexity of biological samples, data acquisition and processing from high throughput techniques (NMR and multidimensional gas chromatography), and search for associations between the instrumental data and metabolic pathways or clinical parameters will be also discussed. Acknowledgments: Funding is acknowledged from the FEDER through the COMPETE Programme and from the FCT, Portugal, under projects PEst-C/QUI/UI0062/2013 (Research Unit 62/94 QOPNA), and PTDC/QUI-QUI/117803/2010.
Samara Silva de Souza
Federal University of Santa Catarina, Brazil
Title: Systems Biology of nanocellulose synthesis: new approach to build a core metabolic model based on computational analysis
Time : 15:20-15:40
Biography:
Samara Silva de Souza is currently a PhD student and researcher at the Chemical Engineering Department of the Federal University of Santa Catarina. Her research interests include Genomics and Bioinformatics and Systems Biology. The Integrated Technologies Laboratory's - InteLab major goal is to integrate multidisciplinary researches, particularly those that unify molecular biology and chemical engineering interests. The InteLab works in the fields of Genome Engineering (Bioinformatics, Metabolic Engineering, and Applied Genomics) and Chemical and Biological Reactors, aiming to develop innovative processes and products for chemical, biotechnological and medical applications. Her thesis concentrated on the study of metabolic network reconstructions, in particular, a bacterium which has been used for nanocellulose biosynthesis. The importance of nanocellulose-based is particularly for tissue engineering applications. Through these researches she acquired different skills in the area of Systems biology and acquainted with different tools and analysis.
Abstract:
Systems biology is a new field that aims to focus on molecular components to understand biological systems. The systematic approach to biology is not new, but it has recently gained new attraction due to emerging experimental and computational methods. Reconstruction of genome-scale metabolic models based on a combination of genome sequence and biochemical information have influenced the field of systems biology in the past decade. Different approaches are frequently used to identify the components of the system and their interactions, to build in silico models that explain complex cellular processes and make testable predictions, as well as to represent these relationships using different computational resources. The Gram-negative bacterium Gluconacetobacter hansenii has been extensively used for nanocellulose synthesis and the recent availability of its genome sequence allows the development of metabolic models of the production of bacterial nanocellulose by integrating typical experimental work with genomic and high-throughput post-genome data. However, despite the importance of bacterial cellulose-based biomaterials particularly for tissue engineering applications, a core metabolic model of its biosynthesis has not been proposed so far. The constraint-based reconstruction and flux analysis approach was used to analyze the model and simulate different conditions to evaluate its consistency and representativity for cellulose biosynthesis. The reconstruction process involves the following steps: 1) creation of a draft model using automated resources, 2) manual curation to construct the core model, 3) conversion of the model into a mathematical format and, 4) biological and biochemical analysis of the network. A core metabolic model developed can provide strategies for developing these biomaterials through a better knowledge of G. hansenii metabolic pathways and elevate our capability for understanding the metabolic capacity under perturbations such as environmental changes.
Nabil Semmar
Institut Supérieur des Sciences Biologiques Appliquées de Tunis, Tunisia
Title: A new computational approach to graphically highlight regulation relationships in metabolic systems from chromatographic data
Time : 15:40-16:00
Biography:
Nabil Semmar is specialized in computational biology focusing his scientific researches on analysis of regulation laws of structural diversity and functional variability in biosystems. He is a multidisciplinary biologist with a long academic itinerary including Master’s in Environmental Sciences (marine and terrestrial), a PhD in Phytochemistry and Post-doctoral researches in Pharmacometrics and Pharmacokinetic Modeling (1988-2004). In his PhD (Lyon, 2000), he developed an original simplex approach helping to statistically highlight multidirectional (flexible) relationships between biological components of polymorphic systems. His finding concerning simplex control of complex biosystems was appreciated by IAEA who invited him as consultant and speaker for conference in scientific program on plant and animal resources management (Vienna, 2008). More recently, he showed the ability of simplex approach to extract hysteretic regulation laws between drug metabolites in pharmacokinetic populations (2010). Moreover, his statistical contributions in pharmacometrics and population pharmacokinetics modeling were appreciated by Biomedical Simulations Resource Group (California) who invited him as speaker for a conference (Los Angeles, 2007). In pedagogy, he is the author of three books on statistics, computational metabolomics and chemotaxonomy in addition to several book chapters published in different international publishers (since 2009). He is Associate Professor at the University of Tunis (ISSBAT) (Tunisia) where he teaches these fundamental and specialization fields in different licenses and masters of biological sciences.
Abstract:
A new computational approach was developed to highlight some metabolic order by statistically exploring the variability between and within chromatographic profiles representing different states in the studied population. The approach consisted in combining metabolic variability of chromatographic profiles initially classified into metabolic trends (MbTrs). Illustration was based on 248 profiles of plasmatic L-dopa and its metabolites (3-OMD, DOPAC and HVA) analysed at different times (after L-dopa administration) in 34 patients suffering from Parkinson disease. After statistical classification of the population into different MbTrs, classified profiles were iteratively combined in silico by applying a Scheffé’s mixture design. To take into account the variability within and between MbTrs, the mixture design was iterated k times by bootstrap leading to k response matrices that were averaged to obtain a complete set of smoothed profiles representing gradual regulations between metabolites. Smoothed response data were used to graphically analyse backbone of the metabolic system. The results highlighted MbTr-dependent relationships between metabolites, revealing high metabolic flexibility. Apart from this static application, the same iterative algorithm was applied to separate data subsets corresponding to different sampling times. From 3-D plots (time t, metabolite x, metabolite y), smoothed results highlighted a counter-clock hysteresis between a precursor (DOPAC) and its derivative (HVA) suggesting a lag between metabolic regulations; such a process was compatible with the metabolic pathways.