Overview
This (online) joint symposium aims to explore areas of research priorities, complementary strengths, and avenues to further strengthen collaborative partnership between National Centre for Infectious Diseases (NCID), Imperial College London (ICL) and NTU Singapore’s Lee Kong Chian School of Medicine (LKCMedicine).
This event is open to all participants from National Centre for Infectious Diseases and Department of Infectious Diseases, Tan Tock Seng Hospital, Imperial College London and associated NHS Trusts and, Lee Kong Chian School of Medicine.
CME/CPE/CNE points will be awarded for Singapore attendees only (if applicable).
This will be a Zoom meeting. To register for this event, please click “Register now” on the left-hand side of the page (or – for mobile devices – above) or click here.
Registration will close on 31 October 2023.
Agenda
Speaker profiles and synopses
Mechanisms of Immunity Against Malaria by Professor Faith Osier, Department of Life Sciences; Co-Director, Institute of Infection, ICL
Professor Faith Osier is Chair of Malaria Immunology and Vaccinology in the Faculty of Natural Sciences at Imperial College London where she also serves as the Co-Director of the Institute of Infection. She previously led two cross-continental research teams in Kenya and Germany with a vision to “Make Malaria History” through vaccination. Her work focuses on vaccine candidate discovery, the identification of correlates of protection and the mechanisms that underpin protective immunity. Her work has led to international honours and prizes, including the Royal Society Pfizer Prize, the Sofja Kovalevskaja Award, and a UKRI African Research Leader Award. She is a TED Fellow, an EDCTP Senior Fellow and an official #TOGETHERBAND Ambassador for the United Nations Global Goal 3. Faith is the Past President of the International Union of Immunological Societies (IUIS) and was recently awarded the prestigious British Society for Immunology Lifetime Honorary Membership Award.
Synopsis
Passive transfer experiments established the protective role of antibodies in immunity against malaria over half a century ago but the mechanisms that underpin protection are still debated. We first demonstrate the power of contemporary controlled human malaria infection studies to clearly distinguish protected from susceptible volunteers. We then show IgG Fc-dependent effector mechanisms involving complement, natural killer cells, neutrophils and monocytes are much stronger correlates of protection than the widely accepted of inhibition of erythrocyte invasion. Our data suggest that a structure & Fc-function guided approach to malaria vaccine development may be beneficial.
Plasmodium Vivax and Zoonosis Malaria in South East Asia by Professor Laurent Renia, Program Director, Infectious Disease & Professor of Infectious Disease, Lee Kong Chian School Of Medicine
Laurent Renia is currently a professor of infectious diseases and the director of the Respiratory and Infectious Diseases Programme at the Lee Kong Chian School of Medicine and in the School of Biological Sciences, Nanyang Technological University. He is also a senior fellow and principal investigator of the A*STAR ID Labs.
He obtained his Ph.D. in 1991 from University Pierre et Marie Curie (now Sorbonne University) in Paris, France, and did his post-doctoral at New York University (1991-1992) under Victor Nussenzweig. He returned to Paris in 1993 where he obtained a permanent position as a research scientist at the French National Institute of Health (INSERM). Between 2001 and 2006, he became research director at INSERM, co-director, and director of the Department of Immunology at the Institut Cochin. He first joined A*STAR as a senior principal investigator in the Singapore Immunology Network (SIgN) in 2007. He became its Executive Director in 2013 from 2020. In 2020, he founded the A*STAR ID Labs (A*STAR) as its executive director. He holds an adjunct position at the French National Institute of Health (INSERM). His scientific interests cover the immunology of infectious disease, focusing on mosquito-borne and zoonotic diseases, and newly emerging viruses such as SARS-CoV-2. His research focuses on shaping new concepts based on the understanding of molecular and cellular mechanism immunity through the development of animal models and new assays and approaches. He has published more than 390 articles and book chapters.
Synopsis
Malaria remains a serious and persistent threat to public health in many parts of Southeast Asia. It is caused by parasitic protozoans of the Plasmodium. In Southeast Asia, the most prominent species is P. vivax although P. falciparum is also responsible for high morbidity. In addition, several simian Plasmodium species has been shown to infect humans. Zoonotic malaria poses a challenge for malaria elimination efforts in Southeast Asia, as it requires different strategies and interventions than human-only malaria. For example, diagnosis of zoonotic malaria may require molecular methods to distinguish between simian and human Plasmodium species. Treatment of zoonotic malaria may require different drug regimens to prevent drug resistance and relapse. Our lab is interested to understand the biological processes that mediate re-emergence of human parasites and emergence of zoonosis caused by primates Plasmodium parasite species. The malaria parasites have a complex life cycle, with one phase in the mosquito, and another in the mammalian host. In mammals, they first have a phase in the liver and one in the blood. The latter is thought to be the most stringent barrier to host adaptation. In the recent years, we have developed many tools and methods and regional collaborations to study three important and related parasites: P. vivax, P. cynomolgi and P. knowlesi. Using patients and monkey samples, we and others have obtained strong evidence that the host barrier to adaption in humans is the tropism of the parasite to red blood cells, in particular young red blood cells (i.e., the reticulocytes) and a family of proteins called reticulocyte binding proteins (RBPs). We are now further (i) identifying parasite ligands interacting with the erythrocytes, (ii) identifying or confirming human or monkey receptors on erythrocytes recognized by the parasites and with which ligands they interact, with the goal to develop new culture systems/conditions which will help us propagate in vitro species that have never been maintained in vitro and uncover which are the molecular roadblock for zoonosis. This will also help us to design new interventions such as vaccines against these parasites.
The Utility of Randomised Controlled Clinical Trials in Bacteraemia by Professor David Lye, Director, Infectious Disease Research Training Office, NCID
Professor David Lye is the director of Infectious Disease Research and Training Office at National Centre for Infectious Diseases and the deputy executive director of the Programme for Research in Epidemic Preparedness and Response. He is a professor at Lee Kong Chian School of Medicine and Yong Loo Lin School of Medicine. He is a senior consultant at the Department of Infectious Diseases, Tan Tock Seng Hospital. He has chaired the National Antimicrobial Stewardship Expert Panel since 2014. He is a member of National Antimicrobial Resistance Control Committee, One Health Antimicrobial Resistance Project Team and Expert Committee on COVID-19 Vaccination, Ministry of Health, Singapore. Professor Lye is the president of the Society of Infectious Disease (Singapore) and the Asia Pacific Society of Clinical Microbiology and Infection. He is a member of the executive committee of the International Society of Antimicrobial Chemotherapy and council member of the International Society of Infectious Diseases. Professor Lye has published more than 350 peer-reviewed manuscripts in journals such as NEJM, Lancet, JAMA, Lancet Respiratory Medicine, Lancet Infectious Diseases, Lancet Microbe, Lancet Global Health as well as Science, Nature Biotechnology, Nature Microbiology, Nature Communications, Science Translational Medicine, Journal Clinical Investigation and Journal Experimental Medicine. He is a Clarivate Highly Cited Researcher in 2022.
Synopsis
Bacteraemia is associated with significant mortality and strong evidence base in guiding clinical management is necessary. I will review selected recent randomised controlled trials in bacteraemia and emphasise their clinical impact. I will discuss two recent ongoing randomised controlled trials in bacteraemia, INVEST and SNAP, in gram negative and Staphylococcus aureus bacteraemia respectively. There are opportunities for translational research building on these international multicentre trials.
Targeting Bacterial Bioenergetics & Central Metabolism for Drug Development by A/Professor Kevin Pethe, Infectious Disease and Assistant Dean (Research), Lee Kong Chian School of Medicine
Associate Professor Kevin Pethe is known for his contribution in the area of chemical biology and antibiotic drug discovery for tuberculosis and mycobacterial diseases. He has provided fundamental insights into the pathogenesis of Mycobacterium tuberculosis, on microbial bioenergetics, and on strategies to discover novel antibacterial agents. Notably, he led interdisciplinary teams that developed clinical-stage drug candidates for tuberculosis and related mycobacteria. He is teaching microbiology, antibiotic drug development, infectious diseases and pharmacokinetics to undergraduate and graduate students at NTU Singapore’s LKCMedicine, the College of Science, and the College of Engineering. He is also acting as personal tutorial for undergraduate medical students of the Lee Kong Chian School of Medicine. Among other services, he is serving as academic chairperson for the NTU Institutional Biosafety Committee since 2016. Before joining NTU, he gained expertise in Research & Development in the private sector as research investigator and project manager at the Novartis Institute for Tropical Disease (Singapore) from 2004 to 2011. In 2011, he took a position of principal investigator at Institut Pasteur Korea to pursue his interest on host-pathogen interactions and chemical biology applied to tuberculosis and multidrug resistant bacteria. He was promoted to head of the department of disease biology & chemical genomics in 2013, and nominated acting CEO of Institut Pasteur Korea the same year, two positions that refined his leadership skills. His professional experience includes evaluating research grants for various National and international agencies. He is a review panel member for the Open Fund Young Individual Research Grant scheme (Singapore Ministry of Health), and for the French National Research Foundation (ANR). He received his PhD in genetics and molecular biology from Institut Pasteur and University of Lille II (France), and received his postdoctoral training in cellular microbiology at Cornell University.
Synopsis
The rapid emergence and global proliferation of multi-drug resistant bacteria poses an urgent challenge, necessitating the creation of innovative antibacterial agents with unique mechanisms of action. Conventional antibiotics, primarily sourced from nature, typically target a limited range of cellular processes, such as DNA replication, protein synthesis, and cell wall biosynthesis. In light of escalating drug resistance, there is a renewed imperative to explore alternative, essential cellular pathways, including central metabolic and bioenergetics processes, as potential targets of next generation antibiotics. However, validating such targets presents intricate challenges, given their frequent conditional essentiality. Interest in targeting central metabolism has also been muted because of a concern about selectivity with human orthologs.
This presentation aims to underscore the significance of bioenergetics targeting in the rational design of drug combinations for combating tuberculosis and other mycobacterial diseases. Additionally, it delves into the identification of metabolic vulnerabilities in other bacteria that could be exploited for drug development.
Bacterial Effectors and Their Many Ways to Modulate Immune Signaling by Dr Teresa Thurston, Advanced Research Fellow, Department of Infectious Disease, ICL
Teresa Thurston is a BBSRC David Philips Fellow and Senior Lecturer at the Department of Infectious Disease and Centre for Bacterial Resistance Biology at Imperial College London, UK. She obtained her PhD in innate immunity from the University of Cambridge with Dr. Randow and carried out postdoctoral training with Prof. Holden in Salmonella pathogenesis. Research in her group is centred around host-pathogen interactions upon infection with intracellular bacteria.
Synopsis
Many Gram-negative bacteria modulate host immune responses through the activity of effector proteins delivered by secretion systems. The downstream changes mediated by an effector’s enzymatic activity ranges from the highly specific, to the multifunctional. Together their combined action impacts the function of an impressive array of host cellular processes, including signal transduction and the manipulation of innate immune responses. Here, we present a specific example of how an intracellular bacterium reverses a host post-translational modification, to counteract the immune response of the infected cell.