Plenary Lectures

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Plenary 1

 

Balbir Singh

 

Faculty of Medicine and Health Sciences, UNIMAS, Sarawak Malaysia

PLASMODIUM KNOWLESI: PAST, PRESENT AND FUTURE

Abstract


For a considerable period, malaria in humans was thought to be caused by four species of Plasmodium: P. falciparum, P. vivax, P. malariae and P. ovale. Naturally acquired human infections with simian malaria parasites were thought to be extremely rare, until the use of molecular tools lead to the discovery of a large focus of human P. knowlesi infections in 2004 in the Kapit Division of Sarawak, Malaysian Borneo. Human knowlesi malaria cases have since been described throughout Southeast Asia, although Malaysia has reported the highest incidence to date with 7,745 cases in 2017 and 2018. The widespread distribution of human cases, with some resulting in fatal outcomes, underscore the public health importance of human P. knowlesi infections in this region. The talk will begin with a description of the pioneering work of Dr. Knowles and Dr. Das Gupta in India, following their isolation of P. knowlesi from a long-tailed macaque in 1931, and of other early studies leading to the discovery of the large focus of human infections in Sarawak in 2004. More recent epidemiological and entomological data will be presented, together with whole genome-sequencing and other molecular data of P. knowlesi isolates derived from humans and macaques, which indicate that knowlesi malaria is primarily a zoonosis, and that there are at least 3 sub-populations of P. knowlesi. It remains to be seen whether P. knowlesi continues to cause zoonotic infections or whether the loss of the natural habitat of monkeys due to deforestation, coupled with changes in mosquito abundance and feeding behavior, and an increase in the human population, result in P. knowlesi switching to humans as the preferred host.





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Plenary 2

 

Patrick Tan

Singhealth Duke-NUS Institute of Precision Medicine (PRISM) DUKE-NUS Medical School, Singapore

GENOMIC AND EPIGENOMIC PROFILES OF ASIAN ENDEMIC MALIGNANICES

Abstract


Many malignancies with high prevalence in Asia are caused by exposures to carcinogens, such as infectious agents and chemical toxins. Such cancers provide important “natural experiments” for understanding how environmental perturbations can disrupt normal cellular processes to ultimately drive tumour development, at both the genetic and epigenetic level. In this talk, I will describe how genomic approaches have led to important insights into the molecular processes driving various cancers with high-prevalence in Asia. Some of these insights may also prove relevant for treating such Asian cancers.





Abstract


Many malignancies with high prevalence in Asia are caused by exposures to carcinogens, such as infectious agents and chemical toxins. Such cancers provide important “natural experiments” for understanding how environmental perturbations can disrupt normal cellular processes to ultimately drive tumour development, at both the genetic and epigenetic level. In this talk, I will describe how genomic approaches have led to important insights into the molecular processes driving various cancers with high-prevalence in Asia. Some of these insights may also prove relevant for treating such Asian cancers.





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Plenary 3

 

M Madan Babu

MRC Laboratory of Molecular Biology

Francis Crick Avenue, Cambridge Biomedical Campus

Cambridge CB2 0QH, UK

UNDERSTANDING VARIATION IN THE GPCR SIGNALLING SYSTEM

Abstract


G-protein-coupled receptors (GPCRs) participate in diverse physiological processes, ranging from sensory responses such as vision, taste and smell to those regulating behavior, the immune and the cardiac system among others. The ~800 human GPCRs sense diverse signaling molecules such as hormones and neurotransmitters to allosterically activate the associated G proteins, which in turn regulate intracellular signaling. In this manner, GPCRs regulate virtually every aspect of human physiology. Not surprisingly, GPCRs are the targets of over one-third of all prescribed human drugs. In this presentation, I will first discuss how one could leverage data on sequence changes across diverse species to infer selectivity determinants of GPCR-G-protein binding, which is critical to elicit the right intracellular response. I will then discuss how one could exploit data on completely sequenced genomes of over 60,000 individuals from the human population to gain insights into natural receptor variation, which can result in variable drug response. Finally, I will present ongoing work wherein by studying transcriptome data from over 30 different tissues in humans, one could begin to understand how alternative splicing can create diversity in GPCR signaling components, which may contribute to tissue-specific differences in receptor signaling. I will conclude by discussing how understanding variation at these different spatio-temporal dimensions, i.e. across different species, among different individuals of a species, and between tissues of a species, can provide a rich source of new hypotheses with implications for personalized medicine and understanding basic receptor biology.





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Plenary 4

 

Leann Tilley

Department of Biochemistry and Molecular Biology, Bio21 Institute , The University of Melbourne,  Australia

NEW TECHNOLOGIES THAT PROVIDE INSIGHTS INTO MALARIA PARASITE VIRULENCE AND ANTIMALARIAL DRUG DESIGN

Abstract


Tumor-infiltrating lymphocytes (TIL) are associated with survival in virtually every human cancer, but the mechanisms by which they confer protective immunity remain incompletely understood. Focusing on ovarian cancer, our group applies genomic and molecular pathology approaches to define the mechanisms by which the human immune system responds to the evolving tumor genome over space and time. We find that optimal anti-tumor immunity involves interactions between T cells and antibody-producing B cells in the tumor microenvironment. We have evidence that T cell clones track tumor clones over space and time and apply selective pressure that leads to reduced tumor clone diversity and progressive loss of immune recognition through several mechanisms. Our findings suggest new strategies to overcome these challenges through T cell engineering and other approaches. Toward this goal, I will discuss our cancer centre's new clinical trials program focused on T cell engineering strategies for gynecological and lymphoid cancers.





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Plenary 5

 

Noboru Mizushima

Department of Biochemistry and Molecular Biology Graduate School of Medicine, The University of Tokyo, Tokyo , Japan

PHYSIOLOGICAL ROLES AND MOLECULAR MECHANISMS OF AUTOPHAGY

Abstract


Autophagy is a major degradation system in the cell. Intracellular components are sequestered by autophagosomes and then degraded upon fusion with lysosomes. Yeast genetic studies have identified more than 40 autophagy-related (ATG) genes. Many of these genes are conserved in higher eukaryotes, which brought about an exponential expansion of autophagy research in various organisms including mammals. The 2016 Nobel Prize in Physiology or Medicine was eventually awarded to the scientist who spearheaded the rapid development of the field, Dr. Yoshinori Ohsumi. However, there remain many fundamental questions in the autophagy field regarding its physiological roles and molecular mechanisms. For example, selective autophagy has become a hot topic but its precise mechanisms and physiological roles are still under investigation. We recently identified a novel receptor for autophagy of endoplasmic reticulum (ER-phagy). Also, it is now well appreciated that some ATG proteins have autophagy-independent functions or have made interesting evolution. We found that Plasmodium and Toxoplasma have a unique set of ATG proteins that contains a non-covalent type of the ATG12 system instead of the covalent type found in most eukaryotes. In this lecture, these novel findings made in vertebrates and parasites will be discussed.





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Plenary 6

 

Brad Nelson

Co-Director, Immunotherapy Program

BC Cancer, Victoria BC, Canada

DECIPHERING AND RE-ENGINEERING THE IMMUNE RESPONSE TO CANCER

Abstract


Tumor-infiltrating lymphocytes (TIL) are associated with survival in virtually every human cancer, but the mechanisms by which they confer protective immunity remain incompletely understood. Focusing on ovarian cancer, our group applies genomic and molecular pathology approaches to define the mechanisms by which the human immune system responds to the evolving tumor genome over space and time. We find that optimal anti-tumor immunity involves interactions between T cells and antibody-producing B cells in the tumor microenvironment. We have evidence that T cell clones track tumor clones over space and time and apply selective pressure that leads to reduced tumor clone diversity and progressive loss of immune recognition through several mechanisms. Our findings suggest new strategies to overcome these challenges through T cell engineering and other approaches. Toward this goal, I will discuss our cancer centre's new clinical trials program focused on T cell engineering strategies for gynecological and lymphoid cancers.