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Life Science Session - "Creating New Paradigms"
Dennis Lo

Convener, Keynote speaker and moderator

Professor Lo is the Director of the Li Ka Shing Institute of Health Sciences, the Li Ka Shing Professor of Medicine, and the Professor of Chemical Pathology of The Chinese University of Hong Kong (CUHK). He discovered the presence of cell-free fetal DNA in maternal plasma. He and his colleagues are instrumental in making non-invasive DNA-based prenatal testing a clinical reality. His team developed a Down syndrome test that has been adopted in over 90 countries and has been used by over two million pregnant women. With the use of massively parallel sequencing and the development of novel bioinformatics strategies, Professor Lo’s group also succeeded in deciphering a genome-wide genetic map of the fetus through the analysis of traces of fragmented DNA floating in the blood of pregnant women. This scientific achievement lays the foundation for developing non-invasive prenatal diagnostic tests for multiple genetic diseases. To recognise his outstanding contributions, Professor Lo is the recipient of numerous awards, for example, the 2015 AACC Wallace H. Coulter Lectureship Award, the 2016 Life Science Prize of the Future Science Prize and the 2021 Breakthrough Prize in Life Sciences, and the 2022 Lasker-DeBakey Clinical Medical Research Award. Professor Lo is a founding member of the Hong Kong Academy of Sciences.

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Title of the talk: 

Circulating DNA Molecules in Plasma: Coming all Sizes and Shapes.

Synopsis:

Cell-free DNA in plasma has made possible the development of non-invasive prenatal testing (NIPT) and cancer liquid biopsies. My group is interested in the molecular characterisation of such molecules. Such molecules have been found to consist of short fragments of DNA. The fragmentation has been found to be non-random. The study of such fragmentation is now called fragmentomics. Very recently, through the use of single molecule sequencing, we have found that there is a previously undiscovered population of 'super long' cell-free DNA in plasma. The discovery of such molecules has opened up new possibilities for plasma-based molecular analysis.

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Nancy Ip

Keynote speakers and panelists

Professor Ip is currently the Morningside Professor of Life Science and the Director of the State Key Laboratory of Molecular Neuroscience at The Hong Kong University of Science and Technology (HKUST). She is also the President of HKUST and a founding member of the Hong Kong Academy of Sciences. Professor Ip’s major research interests are in neural development and function, as well as drug discovery for neurodegenerative diseases, including Alzheimer’s diseases. She is well-known for her seminal discoveries in the biology of neurotrophic factors, which are proteins that promote the survival, development, and maintenance of neurons in the nervous system. In addition, she has also contributed significantly towards understanding the molecular mechanisms underlying brain development and synaptic plasticity, and their dysregulation in neurological disorders. She has published over 320 scientific papers, and holds 70 patents. Professor Ip's outstanding achievement has earned for her numerous awards and honours, inclduing the State Natural Science Awards (China’s highest honour in the natural sciences), the L’OREAL-UNESCO for Women in Science Award (making her the first honouree in life sciences from China), and the “Chevalier de l'Ordre National du Mérite” (National Order of Merit) by the French Government. Professor Ip also plays a key role in promoting science and technology in Hong and is active in many relevant Government committees.

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Title of the talk: 

Circulating Proteins: Potential Game Changers in the Diagnosis and Treatment of Alzheimer’s Disease

Synopsis:

Alzheimer’s disease (AD) is a neurodegenerative disease; major hurdles in disease management is the lack of objective diagnostics for early detection and effective treatments. Researchers have long focused on the classical pathological hallmarks of AD to develop diagnostic biomarkers and identify cellular targets in the brain for therapeutic intervention. Recent technological advancements have led to breakthroughs in both diagnostic biomarkers and treatment strategies. Through large-scale blood proteome profiling, we identified a panel of blood proteins for the early detection, diagnosis, and staging of AD. Moreover, we identified a circulating protein, soluble ST2 (sST2), an inhibitor of the cytokine interleukin 33 (IL-33) and its receptor signaling, as a novel disease-causing factor for AD. Elevated levels of circulating sST2 impairs microglial clearance of amyloid-beta, resulting in more severe amyloid pathology. These findings suggest that circulating proteins may be developed as novel diagnostic tools and therapeutic targets of AD and provide insights on the development of precision medicine for the disease.

KY Yuen

Professor Yuen is a microbiology, a surgeon and a physician. He is the Henry Fok Professor in Infectious Diseases, Chair of Infectious Diseases and the Co-Director, State Key Laboratory of Emerging Infectious Diseases of the University of Hong Kong. Professor Yuen is also the Chief of Service, Department of Microbiology of the Queen Mary Hospital and a founding member of the Hong Kong Academy of Sciences. Professor Yuen made his mark in 2003 when the outbreak of Severe Acute Respiratory Syndrome, or SARS, gripped the globe. He played a key role in the discovery of the coronavirus causing the disease and thus leading to measures crucial to containing its outbreak. Professor Yuen is among the world’s top 1% researchers, as ranked by the Essential Science Indicator (ISI web). He has published more than 700 papers in peer reviewed journals, with over 25,000 citations. His success is exemplified by his numerous Fellowships at distinguished institutions, including the Hong Kong Colleges of Pathologists, Surgeons and Physicians, the Royal College of Physicians (Lond and Edin), Surgeons (Glas) and Pathologists (UK), and the American College of Physicians, and the Chinese Academy of Engineering in 2007. He has also contributed substantially to society and awarded the Justice of Peace and the Silver Bauhinia Star by the Hong Kong SAR Government.

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Title of the talk: 

Tackling Emerging Infections: From SARS-03 to COVID-19

Synopsis:

Animal surveillance in Hong Kong SAR between 2003 to 2019 has identified over 30 novel coronaviruses (CoV). Some of these viruses or their close relatives have subsequently jumped into humans several years later. This is best exemplified by the bat SARS related CoV found in 2005 which turns out to be the ancestral virus of 2003 SARS-CoV-1 and 2019 SARS-CoV-2. The bat CoV -HKU4 and -HKU5 are closely related to the human and camel MERS-CoV of the 2012 outbreak in Middle East. The relative of porcine DeltaCoV-HKU15 found in 2012 was reported to infect Haitian children in 2021. However, often only the full genome sequences of these 30 novel animal CoVs are available because the majority of them cannot be cultured in vitro. Since most of these animal CoVs are found in enteric specimens while human CoVs are more often found in respiratory specimens, we use adult stem cells harvested from bat intestinal tissue and human lung tissue for setting up three dimensional (3D) organoids for the isolation and characterization of some CoVs known to have one health or public health significance. Multiplexed rapid diagnostic assay, broad spectrum antiviral, versatile vaccine platform, and reusable personal protective equipment are also important in preparedness against future pandemics.

Ting ZHU

Chair Professor, School of Life Sciences, Westlake University 1999-2003 B.E. in Engineering Mechanics (early graduation with highest honour), Tsinghua University 2003-2005 M.S. in Mechanical Engineering, MIT (Advisor: Roger D. Kamm) 2005-2010 Ph.D. in Biomedical Engineering, Harvard-MIT Division of Health Sciences and Technology (Advisor: Jack W. Szostak) 2010-2011 Postdoctoral Associate, MIT/Massachusetts General Hospital (Advisors: Maria T. Zuber, Gary Ruvkun) 2011-2016 Assistant Professor, School of Life Sciences, Tsinghua University 2016-2019 Associate Professor, School of Life Sciences, Tsinghua University 2019-2022 Professor, School of Life Sciences, Tsinghua University 2022-present Chair Professor, School of Life Sciences, Westlake University

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Title of the talk: 

Building Mirror-Image Biology Systems

Synopsis:

The overwhelmingly homochiral nature of life has left a puzzle as to whether mirror-image biology systems based on a chirally inverted version of molecular machinery could also exist. We initially developed a proof-of-concept mirror-image genetic replication and transcription system based on a synthetic 174-aa mirror-image African swine fever virus polymerase X (ASFV pol X), followed by a more efficient and thermostable 352-aa mirror-image Sulfolobus solfataricus P2 DNA polymerase IV (Dpo4) that led to the realisation of mirror-image PCR, gene transcription, reverse transcription, as well as mirror-image DNA and RNA sequencing. Toward building a mirror-image ribosome, we realised the assembly of mirror-image 5S ribonucleoprotein complexes, protein translation without aminoacyl-tRNA synthetases, and ribozyme-catalysed mirror-image tRNA charging. More recently, we chemically synthesised a 90-kDa high-fidelity mirror-image Pfu DNA polymerase, enabling the accurate assembly of a kilobase-sized mirror-image gene and biostable storage of an entire paragraph of digital text in mirror-image DNA. We also developed a ‘mirror-image selection’ scheme for the directed evolution and selection of biostable L-DNA aptamers from large randomised L-DNA libraries. Our work is a small step toward building mirror-image biology systems. It also highlights the potential to exploit mirror-image biomolecules as a unique class of therapeutic and informational tools.

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