Commensal gut bacteria-derived microvesicles: Mediators of microbe-host crosstalk and vehicles for drug delivery.
Keynote & Invited lecturers
Prof. Simon Carding (UK)
Completed postgraduate work at the Medical Research Council’s Clinical Research Centre then postdoctoral work at New York University School of Medicine and Yale University prior to a faculty position at the University of Pennsylvania, Philadelphia and the development of a research programme focusing on gut biology and immunology. Returned to the UK and the University of Leeds to develop a new programme of research focusing on commensal gut bacteria leading to the development of a Bacteroides drug delivery technology platform for the development of new treatments for GI-related diseases. Relocated to the Quadram Institute and Univ. East Anglia to develop and lead a multidisciplinary Gut Biology Research Programme. A current focus is using commensal gut bacteria derived microvesicles for boosting natural immunity in at risk individuals, and for the delivery of therapeutic proteins and vaccine antigens to mucosal sites to treat or prevent autoimmne- or infection-related diseases that target the GI-tract and the brain (the gut-brain axis). .
TALK: Commensal gut bacteria-derived microvesicles: Mediators of microbe-host crosstalk and vehicles for drug delivery.
Talk abstract : The human gastrointestinal tract is home to hundreds of trillions of microorganisms (the microbiome) that perform a vital role in food digestion and providing essential nutrients and vitamins. They also play an important role in metabolizing medicines and drugs, and in resisting infection by pathogens. Gut microbes are however susceptible to change with alterations in their makeup and activity occurring as a result of exposure to various environmental factors such as diet, drugs, pathogens and behaviour. Such changes have been associated with more than 90% of human diseases affecting the gut, liver, joints, heart and brain. A central question to discriminating between association and causality is, how do gut microbes communicate with their host to affect physiological changes at the cellular and organ level within the gut and beyond? We have uncovered roles for microbiota-derived metabolites and highly stable, nanosized microvesicles (outer membrane vesicles; OMVs) naturally produced in the gut by prominent members of the intestinal microbiota in cross-kingdom communication. We have shown that specific microbial metabolites can affect various tissues including the blood brain barrier and that OMVs can bring about changes in host cell physiology by delivering various cargo including metabolic enzymes and mediators of intracellular signaling. Via their ability to cross the intestinal epithelium and access the lymphatic and vascular system they can also affect cells and tissues throughout the body and via interactions with the blood brain barrier, access the brain. Furthermore, we have exploited this OMV-mediated cross-kingdom communication pathway to develop a drug delivery technology platform using OMVs to deliver therapeutic proteins and vaccine antigens directly to mucosal tissues. Pre-clinical studies highlight the utility of this technology in both boosting natural immunity and in preventing and treating infection and autoimmune mediated pathologies that affect the gut and other tissues, with a particular interest in neurological disorders including dementia.
Ana L. Carvalho, Sonia Fonseca, Ariadna Miquel-Clopés, Kathryn Cross, Khoon-S. Kok, Udo Wegmann, Katherine Gil-Cardoso, Eleanor G. Bentley, Sanaria H.M. Al Katy, Janine L. Coombes, Anja Kipar, Regis Stentz, James P. Stewart & Simon R. Carding (2019) Bioengineering commensal bacteria-derived outer membrane vesicles for delivery of biologics to the gastrointestinal and respiratory tract, Journal of Extracellular Vesicles, 8:1, DOI: 10.1080/20013078.2019.1632100
Joseph Foley is a research scientist at the Stanford University School of Medicine. In the laboratory of Prof. Robert B. West, he applies laser-capture microdissection and single-cell technologies to study the functional genomics of the tumor microenvironment in breast cancer. Dr. Foley has been pioneering molecular biology and bioinformatics techniques for next-generation sequencing since the early days of the technology. He carried out his dissertation research in with Prof. Arend Sidow at Stanford University, using a new approach in large-scale ChIP-seq analysis to map the behavior of dozens of transcription factors at high-occupancy target regions. At Stanford he also assisted in the development of 3SEQ, a streamlined gene-expression profiling method that is robust to RNA degradation. He expanded on this work in his postdoctoral research in neurogenomics with Prof. Michael Meaney at McGill University's Douglas Hospital Research Centre, where he combined 3SEQ with other recent innovations to create a much more efficient and sensitive method, Smart-3SEQ. He then returned to Stanford to adapt Smart-SEQ to tissue samples from laser-capture microdissection. Together these techniques unlock gene-expression profiling from very small samples of fixed archival tissue, including single cells, which enables new approaches in molecular pathology and histology-directed genomics.
TALK: Gene-expression profiling of single cells from archival tissue with laser-capture microdissection and Smart-3SE.
Recent publication :
Joseph W. Foley, Chunfang Zhu, Philippe Jolivet, Shirley X. Zhu, Peipei Lu, Michael J. Meaney and Robert B. West. Gene expression profiling of single cells from archival tissue with laser-capture microdissection and Smart-3SEQ. Genome Res. 2019. 29: 1816-1825 doi: 10.1101/gr.234807.118
Amanda Kedaigle is a Computational Biologist at the Broad Institute and Harvard University, working with the groups of Paola Arlotta, Joshua Levin, and Aviv Regev. Her research leverages transcriptomic and epigenomic data from brain organoids to gain insight into human development and psychiatric disorders. She received her Ph.D. in Computational and Systems Biology from MIT in 2018, where she applied novel tools combining 'omic data modalities to the study of Huntington's Disease, in the lab of Ernest Fraenkel. She also holds a Graduate Education in Medical Sciences certification from the Institute for Medical Engineering and Science, and a B.A. in Bioinformatics from Wellesley College.
TALK: Evaluating the reproducibility and fidelity of human brain organoids using single cell data.
Recent publication :
Velasco, S., Kedaigle, A.J., Simmons, S.K. et al. Individual brain organoids reproducibly form cell diversity of the human cerebral cortex. Nature 570, 523–527 (2019).
Mikael Kubista (Czech Republic)
Institute of Biotechnology Czech Academy of Sciences.
TALK: Two-Tailed PCR for Precision Molecular Analyses.
Prof. Joakim Lundeberg (Sweden)
Professor Joakim Lundeberg of the Department of Gene Technology focuses on molecular technology development. Since May 2010, his research group has been located at the Science for Life Laboratory (SciLifeLab), a national center for molecular biosciences with focus on health and environmental research. The center combines frontline technical expertise with advanced knowledge of translational medicine and molecular bioscience. His current research focus relates to spatially resolved gene expression studies in situ, Spatial Transcriptomics. RNA-sequencing offers the possibility to analyze the expression of all genes in a sample. However, the spatial information of gene expression is lost. In the pioneering work a method was described that allowed studies of gene expression in tissue sections using RNA-sequencing to uncover transcriptional patterns in situ (Ståhl et al, Science, 2016). Applying this strategy has been demonstrated to work remarkably well and allows visualizing and quantifying the transcriptome in regular histological tissue sections, i.e. tissue domains can be matched to precise gene expression patterns. Furthermore, data driven methods can be applied to discover in an unsupervised manner transcriptomic patterns in space. Such patterns correspond to cell-types, microenvironments, or tissue components that allow for novel avenues of research.
Daan Noordermeer (France)
Daan Noordermeer obtained his PhD in 2009 from the Erasmus University (Rotterdam, The Netherlands), working with Wouter de Laat and Frank Grosveld on the 3D genome organization of the mouse beta-globin locus. He then moved to the Ecole Polytechnique Fédérale de Lausanne (EPFL, Switzerland) for a postdoc with Denis Duboule. Here, he was among the first to report an intimate link between 3D genome organization, histone modifications and gene regulation (Noordermeer et al., Science 2011). Since 2014, he is a tenured researcher at the CNRS (French National Center for Scientific Research) and he heads the Chromatin Dynamics group at the I2BC (Institute for Integrative Biology of the Cell, Gif-sur-Yvette - France). With his team, he continues the investigation into the links between genome structure and epigenetic mechanisms using a mix of genomics and single-cell approaches in the context of stem cells, aging and cancer.
Michael W. Pfaffl (Germany)
In 1986, Michael W. Pfaffl started studying ‘Agriculture - Animal Science’ and ‘Biotechnology’ at the Technical University of Munich (TUM). In 2010 he became Professor of ‘Molecular Physiology’ at the TUM School of Life Sciences in Weihenstephan. Today he has reached the ‘Principal Investigator’ status at the Institute of Animal Physiology & Immunology and is one of the leading scientists in the field of Gene Quantification, RT-qPCR technology, RNA sequencing, EV transcriptomics, and complex data analysis in expression profiling. He is author of around 210 peer-reviewed publications, 50 book chapters, and has held more than 270 lectures worldwide. In March 2012 the Elsevier SciVerse Scopus Award 2012 was granted to Prof. Michael W. Pfaffl, whose top cited Scopus article entitled "A new mathematical model for relative quantification in real-time RT-PCR" published 2001 in Nucleic Acids Research 29(9) which has been cited today more than 21,800 times. He is coauthor of the Minimum Information for Publication of Quantitative Real-Time PCR Experiments (MIQE) guidelines (2009) and coauthor of the dMIQE guidelines for digital PCR (2013). Professor Michael W. Pfaffl has editorial involvements as Founding- & Section-Editor in ‘Biomolecular Detection and Quantification’, Editor in ‘Methods’ and ‘International Journal of Oncology’, and Editor-in-Chief of the ‘Gene Quantification’ webportal, the world’s biggest webpage around qPCR, dPCR and Gene Expression profiling techniques and applications. He is initiator and lead organizer of the qPCR, dPCR & NGS Gene Quantification Event series in Freising Weihenstephan in Germany since 2004 (https://www.eConferences.de);
TALK: Michael’s talk will be focused on Transcriptional Biomarkers in Liquid Biopsies – applying small-RNA Seq and RT-qPCR to identify valid ‘Biomarker Signatures’ in blood and circulating extracellular vesicles.
Sophie Rome (France)
Sophie Rome obtained her PhD in 1996 from the University of Lyon (molecular biology, bioinformatics, microbial ecology). She holds the position of Scientific Director in the department of Human Nutrition of the French INRAE institut in Lyon. Her research focus relates to the role of extracellular vesicles in the development of metabolic diseases (obesity, diabetes, dyslipidemia) and in the regulation of skeletal muscle (SkM) mass. Her group has demonstrated that SkM-released extracellular vesicles are involved in the process of myogenesis and can transfer deleterious lipids and miRNAs into insulin-sensitive tissues during the development of diet-induced obesity. In parallel, she has worked on blood circulating miRNAs to predict the development of diseases associated with diabetes like nephropathies. Recently she has developed an active research program to determine the impact of editable plant-derived extracellular vesicles on the metabolism and whether they could be used as nutritional strategies in the prevention and treatment of intestinal complications associated with obesity. Sophie Rome is the president of the French Society of Extracellular Vesicles which gathers more than 200 laboratories in France (www.fsev.fr).
TALK: Biological Functions of Plant-Derived Extracellular Vesicles: good and bad odds.
Scientific Director in the Department of Human Nutrition at INRAE Institut, FRANCE
Investigator at CarMeN Laboratory
Daniel Rosenberg (USA)
Dr. Daniel W. Rosenberg obtained his Doctoral Degree in Environmental Health Sciences at the University of Michigan. He began his research career in molecular pharmacology at The Rockefeller University in the Laboratory of Attallah Kappas, where he attained the rank of Assistant Professor. After moving to the University of Connecticut in 1991, he was appointed as the HealthNet, Inc. Chair in Cancer Biology and Professor of Medicine in the School of Medicine. He has developed an active research program that focuses on the pathogenesis of gastrointestinal diseases and has also established a translational research program in Colon Cancer Prevention, serving as its Director. The long‐term goals of the Program are to improve the early detection of cancer, develop population‐based studies of cancer risk and develop effective chemoprevention strategies for the treatment of high‐risk individuals. Dr. Rosenberg has published a number of recent papers that define the epigenetics of early human neoplasia in the colon, as well as the mutational, transcriptional and microbiome profiles that are associated with neoplastic progression. Research in the Rosenberg Lab extends across a wide range of research topics in colon cancer biology, applying sophisticated mouse genetic cancer models to further our understanding of carcinogenic mechanisms and to identify novel chemoprevention strategies. He is particularly interested in how nutrition influences cancer risk via changes to the microbiome, thereby affecting colonic homeostasis both in healthy and diseased tissues. As part of his nutritional-cancer approach, his lab has a particular interest in how prostaglandins and one-carbon metabolism may be therapeutically targeted for providing durable cancer prevention.
TALK : I would like to speak about the use of laser capture microdissection to characterize the stromal-epithelial interactions that drive early colonic neoplasia (human and mouse). I will also talk about how LCM can be used to capture small numbers of colonic crypt stem cells defined by specific immunological markers (e.g. Lgr5, Bmi1, Dclk) and how these stem cell populations acquire somatic mutations and respond to specific environmental (microbiome, inflammatory) challenges. I believe that LCM has advantages over single cell analyses in that it maintains the 3-dimensional structure of the tissue, allowing one to visualize specific cell behavior within the intact tissue architecture.
Jo Vandesompele is full professor in Functional Cancer Genomics and Applied Bioinformatics at Ghent University, Belgium. He obtained a Master of Science in Bioscience Engineering (1997) and a PhD in Medical Genetics (2002). Jo is also co-founder and Chief Scientific Officer at Biogazelle, a CRO specializing in high-value genomics applications to support pharmaceutical research, clinical trials and diagnostic test development. He is author of more than 250 scientific articles in international journals, including some pioneering publications in the domain of RNA quantification and non-coding RNA. His H-index is 66, with 33 000 citations. The lab’s research aims to exploit RNA for diagnostic and therapeutic purposes. The various research lines converge on studying the role of non-coding RNA in cancer and on the utility of extracellular RNA in liquid biopsies.
TALK : Extracellular RNA profiling in human biofluids: about standardization and beyond microRNAs and plasma.
Everaert, C., Helsmoortel, H., Decock, A. et al. Performance assessment of total RNA sequencing of human biofluids and extracellular vesicles. Sci Rep 9, 17574 (2019).
Eva Hulstaert E., Annelien Morlion, Francisco Avila Cobos, Kimberly Verniers, Justine Nuytens, Eveline Vanden Eynde, Nurten Yigit, Jasper Anckaert, Anja Geerts, Pieter Hindryckx, Peggy Jacques, Guy Brusselle, Ken R. Bracke, Tania Maes, Thomas Malfait, Thierry Derveaux, Virginie Ninclaus, Caroline Van Cauwenbergh, Kristien Roelens, Ellen Roets, Dimitri Hemelsoet, Kelly Tilleman, Lieve Brochez, Scott Kuersten, Lukas Simon, Sebastian Karg, Alexandra Kautzky-Willers, Michael Leutner, Christa Nöhammer, Ondrej Slaby, Gary P. Schroth, Jo Vandesompele, Pieter Mestdagh. Charting extracellular transcriptomes in The Human Biofluid RNA Atlas. bioRxiv 823369;