Day 2 :
Scientific Advisor Royal Dutch Navy, Netherlands
Time : 08:30-09:10
Stef Stienstra is a Strategic and Creative Development Manager in Biomedical Science, who works internationally for several medical and biotech companies as Scientific Advisory Board Member. He is also an active Reserve-Officer of the Royal Dutch Navy in his rank as Commander (OF4). For the Dutch Armed Forces, he is CBRNe specialist with focus on (micro)biological and chemical threats. He is also Manager of the group of medical- and environmental functional specialists within the 1st CMI (Civil Military Interaction) Battalion of the Dutch Armed Forces. In his civilian position, he is at this moment developing with MT-Derm in Berlin (Germany), a novel interdermal vaccination technology as well as a new therapy for cutaneous leishmaniasis for which he has won a Canadian ‘Grand Challenge’ grant. With Hemanua in Dublin (Ireland), he has developed an innovative blood separation unit, which is also suitable to produce convalescent plasma for Ebola Virus Disease therapy. He has finished both his studies in Medicine and in Biochemistry in The Netherlands with a Doctorate and has extensive practical experience in cell biology, immuno-haematology, infectous diseaases, biodefense and transfusion medicine. His natural business acumen and negotiation competence helps to initiate new successful businesses, often generated from unexpected combinations of technologies. He consults at top level management, in which his good understanding of abstract science combined with excellent skills in communication of scientific matters to non-specialists helps to get things done.
As curative medicine gets, compared to public health systems, generally more attention and financial support, particularly the underdeveloped countries are not well enough prepared for outbreaks of infectious diseases. In the past several Western public health institutes, like the French ‘Institut Pasteur’, the Dutch ‘Tropeninstituut‘, and many others, were prominent surveyors of contagious diseases and very active in the international mitigation of infectious diseases. In the last decennia, the investments in worldwide public health unfortunately have been reduced compared to curative healthcare. With the recent Ebola Virus Disease outbreak in West Africa, we see a new wave of growing interest to invest in Worldwide Public Health to prevent spreading of highly contagious diseases. Most public health systems in developing countries do not have proper diagnostic laboratories, quarantine procedures and treatment facilities. Non-Governmental Organisations (NGOs) helping to fight outbreaks are often better trained in curative treatments and have less skills with biological (bioweapon) threats in which military have more experience. I acclaim Bill Gates’ announcement in the New England Journal of Medicine (Bill Gates, NEJM, March 19, 2015) that all countries should identify trained military resources that would be available for outbreaks and work together to fight epidemics. New diagnostic technologies will help us worldwide in the defence against emerging contagious diseases. Especially in PCR-based systems, which are nowadays quite ruggedized, are very promising in the identification of potential outbreaks of infectious diseases in wildlife, cattle and/or the human population in developing countries.
Helmholtz Centre for Infection Research, Germany
Keynote: Global reprogramming of the Yersinia pseudotuberculosis transcriptional landscape in response to host signals
Time : 09:10-09:50
Petra Dersch graduated in Microbiology at the University of Konstanz and at the Max-Planck-Institute for Terrestrial Microbiology Marburg. She worked as a Postdoc at the Tufts Medical School, Boston/USA, started her own group at the Freie Universität Berlin, and was Junior Research Group Leader at the Robert Koch Institute Berlin. In 2005, she was appointed at the Technische Universität Braunschweig as Associate Professor in Microbiology, and since 2008, she is Head of the Department of Molecular Infection Biology at the Helmholtz Centre for Infection Research in Braunschweig. She is member of various boards, and a current member of the study section, “Microbiology, Virology and Immunology” of the DFG. Since 2016, she is one of the Vice Presidents of the German Society for Hygiene and Microbiology. Her main research field is Molecular Pathogenesis of Enteric Pathogens. She published more than 90 original papers in peer-reviewed international journals, reviews and book chapters.
Yersinia pseudotuberculosis evolved numerous strategies to survive in environmental reservoirs and mammalian hosts. A hallmark is the ability to rapidly adjust the lifestyle upon host entry to prevent attacks by the host immune systems. The pathogen employs a plethora of control elements to fine-tune regulatory networks. To capture the range, magnitude and complexity of the underlying control mechanisms, we used comparative RNA-seq-based transcriptomic profiling under infection-relevant conditions in vitro and during the infection process in mice. We identified riboswitch-like RNA elements, a set of antisense RNAs, and previously unrecognized trans-acting RNAs, which are differentially regulated under infection conditions. We revealed a temperature- and host-induced reprogramming of important metabolic pathways, virulence traits, and discovered CRP as master regulator of non-coding RNAs. Individual regulatory RNAs, which are differentially regulated during infection, were characterized and their role in infection was elucidated using mouse infection models. Among the regulatory RNAs, which are most important for Yersinia virulence, are the Crp-dependent Csr-type regulatory RNAs found to control multiple virulence-relevant metabolic processes. Our finding highlights a novel level of complexity in which the concerted action of transcriptional regulators and non-coding RNAs adjusts the control of Yersinia fitness and virulence to the requirements of their virulent lifestyle.
- Nuss AM, Beckstette M, Pimenova M, Schmühl C, Opitz W, Pisano F, Heroven AK, Dersch P (2017) Tissue dual RNA-seq allows fast discovery of infection-specific functions and riboregulators shaping host-pathogen transcriptomes. Proc Natl Acad Sci USA. 114(5):E791-E800.
- Nuss AM, Schuster F, Roselius L, Klein J, Bücker R, Herbst K, Heroven AK, Pisano F, Wittmann C, Münch R, Müller J, Jahn D, Dersch P (2016) A precise temperature-responsive Bistable Switch controlling Yersinia virulence. PLoS Pathog. 2016; 12(8):e 1006091.
- Wang H, Avican K, Fahlgren A, Erttmann SF, Nuss AM, Dersch P, Fallman M, Edgren T, Wolf-Watz H (2016) Increased plasmid copy number is essential for Yersinia T3SS function and virulence. Science. 353(6298):492-5.
- Righetti F, Nuss AM, Twittenhoff C, Beele S, Urban K, Will S, Bernhart SH, Stadler PF, Dersch P, Narberhaus F (2016) Temperature-responsive in vitro RNA structurome of Yersinia pseudotuberculosis. Proc Natl Acad Sci USA. 113(26):7237-42.
- Nuss AM, Heroven AK, Waldmann B, Reinkensmeier J, Jarek M, Beckstette M, Dersch P (2015) Transcriptomic profiling of Yersinia pseudotuberculosis reveals reprogramming of the Crp regulon by temperature and uncovers Crp as a master regulator of small RNAs. Plos Genet. 2015; 11(3):e1005087.
Queen’s University Belfast & Agri-Food & Biosciences Institute, UK
Keynote: Paramyxovirus receptor interactions: Importance in understanding cross species infection, vaccine design and disease treatment
Time : 09:50-10:35
S Louise Cosby was appointed as the Head of Virology Branch at the Agri-Food and Biosciences Institute, UK, in 2015. She was the Chair of Microbiology in Queen’s University Belfast from 2002 and remains an Emeritus Professor. She is a Fellow of Royal College of Pathologists (London) and Fellow of the Royal Society of Biology, UK. She has served/currently serves on grant/editorial boards: BBSRC, UK; Chair/Member, Science Foundation Ireland; Deputy Chair Professional Development Committee, Microbiology Society, UK; Associate Editor, Journal of Neurovirology, USA; Review Editor, Frontiers in Microbiology; External Assessor for Appointments and Promotions in Medical Microbiology, University of Malaysia. Her research interests are: virus pathogenesis including, virus-receptor interactions, virus-induced immunosuppression and vaccine development. Her work has focused on paramyxoviruses of both human and veterinary interest, with publications/grant funding in this area.
Viruses make use of cell receptors to both enter the cells and regulate cellular processes. We examined 2 important aspects of virus receptor interactions in members of the Paramyxoviridae, measles virus (MV), veterinary viruses (also in morbillivirus genus) and respiratory syncytial virus (RSV), a major cause of bronchiolitis in infants. MV can cause severe complications such as giant cell pneumonia and acute post measles encephalitis. More rarely fatal infections of the CNS, subacute sclerosing panencephalitis and in immunosuppressed individuals, measles inclusion body encephalitis occur. The World Health Organization (WHO) has set goals towards the complete eradication of MV in at least five WHO regions by 2020. We determined that both MV and RSV infection up-regulates TRPV1, TRPA1 and ASICS 3, airway receptors implicated in cough hypersensitivity and broncho-constriction in asthma and chronic obstructive pulmonary disease. We and others have also shown that veterinary morbilliviruses share common cell entry receptors with MV raising the risk of zoonotic infection. MV is thought to have evolved from the now eradicated cattle morbillivirus, rinderpest, by entering the human population during cattle domestication. This highlights the potential consequences of complete withdrawal of MV vaccination after eradication. MV vaccine is live attenuated and has very low risk of reversion, but is unlikely to be acceptable in a MV free world and may only give partial protection against morbillivirus zoonotic infection. Formalin fixed MV and RSV vaccines were used for a period in the 1960’s, but induced an altered immune response and death of some children following later infection. Based on our understanding of cross species infection new vaccines will be required. In conclusion, receptors are important players in cross-species infection as well as drug targets. Approaches to inhibit airway receptors during virus exacerbations, cell entry receptors for MV and veterinary morbilliviruses and vaccine approaches will be discussed.
- Omar S, Clarke R, Abdullah Brady CH, Corry J, Winter H, Touzelet O, Power UF, Lundy F, McGarvey LPA, Cosby SL (2017) Respiratory Virus Infection Up-Regulates TRPV1 and ASICS3 Receptors on Epithelial and Neuronal Cells. Plos One DOI:10.1371/journal.pone.0171681.
- Melia M, Earle JAP EARLE, Abdullah H, Reaney, K, Willet B, Tangy F, Cosby, SL (2014). Use of SLAM, PVRL4 and HB-EGF as Cell Entry Receptors by Phocine Distemper Virus. Plos One 9(8):e106281.
- Abdullah H, Heaney LG, Cosby SL, McGarvey LPA (2014) Rhinovirus up-regulates transient receptor potential channels in a human neuronal cell line: implications for respiratory virus induced cough reflex sensitivity. Thorax 69:46-54.
- Abdullah H, Brankin B, Brady C, Cosby SL (2013) Wild Type Measles Virus Infection Up-Regulates PVRL4 and Causes Apoptosis in Brain Endothelial Cells by Induction of TRAIL. Journal of Neuropathology and Experimental Neurology 72: 681-696.
- Cosby SL (2012) Morbillivirus Cross Species infection: Are humans at risk? Future Virology 7(11):1103-1113.
University of Cambridge United Kingdom
Keynote: Improved antibiotic treatments and vaccines against bacterial diseases: why do we need to understand how the pathogen interacts with the host?
Time : 11:00-11:40
Pietro Mastroeni received a Degree in Medicine and Surgery from the University of Messina, Italy. He moved to the University of Cambridge, UK where he completed his PhD before working at the University of Newcastle, UK and then became a Research Fellow at Imperial College, University of London UK. He is currently a Reader in Infection and Immunity at the University of Cambridge, UK. He has published more than 100 papers in reputed journals, many prestigious review articles, edited two books, and serves as an Editorial Board Member for several international journals.
Bacterial diseases cause approximately six million deaths per year. Antimicrobial resistance is increasing and better vaccines are needed. The prevention and treatment of infections must be underpinned by an in depth knowledge of the biology and pathogenesis of the microbes and their interaction with the immune system. Empirical approaches achieve only partial success and do not allow accurate targeting of medical interventions. The location, growth status, between organs spread and interaction with cells of the immune system are key variables of the infection process that affect the efficacy of vaccine-induced immune responses and antibiotics. Our recent work has been focused on the fundamental bases of the biology of invasive Salmonella infections in the light of immune-deficiencies that predispose humans and other animals to these diseases. We have shown that Salmonella has a pathogenesis that is both intracellular and extracellular, with systemic spread in multiple body tissues and several sophisticated mechanisms that allow the bacteria to evade killing by phagocytes and disseminate in the tissues. Salmonellae are vulnerable to antibodies and complement that lyse the bacteria and/or target them to phagocytes, increasing the antimicrobial functions of host cells. We have identified phagocyte receptors, intracellular killing mechanisms and bacterial evasion strategies that affect phagocyte- and antibody-mediated killing of Salmonella. We have also determined the interactions between pathogen location, growth, spread and the efficacy of antibiotic therapy. This work lays a foundation for the development of better vaccines and antibiotic treatments for Salmonella infections and establishes principles applicable to other systemic bacterial diseases.
- V Radjabova, Pietro Mastroeni, K Skjodt, P Zaccone, B de Bono, J Goodall, E Chilvers, J Juss, D Jones, J Trowsdale, A Barrow (2015) TARM1 is a novel leukocyte receptor complex-encoded ITAM receptor that costimulates proinflammatory cytokine secretion by macrophages and neutrophils. J. Immunol. 195:3149-3159.
- Pietro Mastroeni, O Rossi (2016) Immunology, epidemiology and mathematical modelling towards a better understanding of invasive non-typhoidal Salmonella disease and rational vaccination approaches. Expert Reviews of Vaccines, DOI:10.1080/14760584.2016.1189330.
- Y S Goh, K Armour, M Clark, A Grant, Pietro Mastroeni (2016) IgG subclasses targeting the flagella of Salmonella enterica serovar Typhimurium can mediate phagocytosis and bacterial killing. Journal of Vaccines and Vaccination. 7: 322.
- A Grant, O Oshota, R Chaudhuri, M Mayho, S Peters, S Clare, D Maskell, Pietro Mastroeni (2016) Genes required for the fitness of Salmonella enterica serovar Typhimurium during infection of immunodeficient gp91-/-phox mice". Infect. Immun. 84: 989-997.
- O Rossi, A Grant, Pietro Mastroeni (2017) Effect of in vivo neutralisation of tumor necrosis factor alpha on the efficacy of antibiotic treatment in systemic Salmonella enterica infections. FEMS Microbiology. doi: 10.1093/femspd/ftx002.
Trinity College Dublin, Ireland
Keynote: Investigating the role of histone acetylation in the regulation of flocculation in Saccharomyces cerevisiae
Time : 11:40-12:20
Alastair Fleming is an Assistant Professor in the School of Microbiology and Genetics at Trinity College Dublin, Ireland, where he is the PI of the Yeast Chromatin Group. His research group focuses on the role of ‘chromatin remodelling’ during various biological processes in yeast. Current research areas include the investigation of: (i) the epigenetic signature associated with cellular aging, (ii) the epigenetic regulation of transcription initiation, (iii) epigenetic memory during transcription elongation, and (iv), the chromatin-mediated regulation of flocculation within yeast cell populations.
Flocculation is a stress response whereby yeast cells adhere to each other to form an aggregation which offers protection to those cells within the ‘floc’ against the outside environment. The flocculation phenotype is important in biofilm formation and in industries such as brewing. Flocculation is mediated by the expression of cell wall proteins known as flocculins. These are lectin-like proteins which bind to the mannose residues in the cell walls of neighbouring yeast cells. The dominant flocculin gene in yeast is FLO1, which is regulated by the Tup1-Cyc8 co-repressor and the Swi-Snf co-activator. Although the mechanism of FLO1 repression has been well characterised, the mechanism of FLO1 de-repression is poorly understood. We show FLO1 de-repression in a cyc8 deletion strain is accompanied by Sas3 and Ada2-dependent histone H3 lysine-14 acetylation at the FLO1 promoter and ORF, together with Swi-Snf recruitment and histone eviction at the promoter. In the absence of Ada2 and Sas3-dependent H3 lysine-14 acetylation, Swi-Snf recruitment and histone eviction proceed at the de-repressed FLO1 promoter, but FLO1 transcription is reduced. Following the conditional depletion of Cyc8 via anchor-away, we show RNA polymerase II (RNAP II) is recruited to the de-repressed FLO1 promoter in a bi-phasic manner concomitant with a similar pattern of histone acetylation. In the absence of Sas3 and Ada2-dependent H3 acetylation, histone eviction and RNAP II recruitment at the FLO1 promoter still occur, however RNAP II is absent from the gene coding region. This suggests that in the absence of Cyc8, Sas3 and Ada2-dependent histone H3K14 acetylation is not required for histone eviction and RNAP II recruitment at the FLO1 promoter, but is required to enable transcription elongation to occur.
- Young CP, Hillyer C, Hokamp K, Fitzpatrick DJ, Konstantinov NK, Welty JS, Ness SA, Werner-Washburne M, Fleming AB, Osley MA (2017) Distinct histone methylation and transcription profiles are established during the development of cellular quiescence in yeast. BMC Genomics. 18(1):107.
- Church M, Smith KC, Alhussain MM, Pennings S, Fleming AB (2017) Sas3 and Ada2(Gcn5)-dependent histone H3 acetylation is required for transcription elongation at the de-repressed FLO1 gene. Nucleic Acids Res.
- Haran J, Boyle H, Hokamp K, Yeomans T, Liu Z, Church M, Fleming AB et al. (2014) Telomeric ORFs (TLOs) in Candida spp. encode mediator subunits that regulate distinct virulence traits. PLoS Genet. 10(10).
- Fleming AB, et al. (2014) The yeast Cyc8-Tup1 complex cooperates with Hda1p and Rpd3p histone deacetylases to robustly repress transcription of the subtelomeric FLO1 gene. BBA-GRM. 1839(11):1242-55.
- Barski A, Chepelev I, Liko D, Cuddapah S, Fleming AB, et al. (2011) Pol II and its associated epigenetic marks are present at Pol III-transcribed noncoding RNA genes. Nat Struct Mol Biol. 17: 629-634