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Theme-based Research Scheme - Fifth Round Layman Summaries of Projects Funded

Theme 1: Promoting Good Health
Project Title: Molecular Basis for Interspecies Transmission and Pathogenesis of Middle East Respiratory Syndrome Coronavirus
Project Coordinator: Prof Patrick Chiu-yat WOO (HKU)

Abstract
Global health threats due to emerging infectious agents are exemplified by HIV, influenza virus, SARS coronavirus (CoV) and Ebola virus. Compared to other viruses, CoVs are grossly understudied. The recent emergence of MERS-CoV has alerted the public and WHO, who considered MERS-CoV "a threat to the entire world". Unlike SARS which rapidly died off after the intermediate amplification animal hosts were identified and segregated from humans by closure of wild animal markets in Southern China, the MERS epidemic has persisted for at least two years with a scary fatality rate of >30%. In the past ten years, our group has been taking a lead internationally in discovering and characterizing novel CoVs in animals and human. We identified the largest number of CoVs globally, including SARS-CoV, human CoV HKU1, SARS-CoV-like bat CoVs and most importantly, Tylonycteris bat CoV HKU4 and Pipistrellus bat CoV HKU5 (BatCoV HKU4/5), which are closely related to MERS-CoV and have formed the foundation for identifying the animal origin of MERS-CoV. Our contributions have revolutionized CoV research and provided the ground for in-depth mechanistic studies on CoVs. In the past 24 months we have accumulated several lines of pilot results that lead to the present studies. We have discovered a MERS-CoV-like CoV from bats, even closer to MERS-CoV than BatCoV HKU4/5. We have set up an animal model for MERS-CoV. We have defined novel mechanisms for MERS-CoV evasion of host defense. Built on these findings and unique resources, here we will address three important issues on MERS-CoV. We will identify the evolutionary paths leading to emergence of MERS and mechanisms of interspecies transmission. We will delineate molecular mechanisms by which MERS-CoV evades innate immunity. Lastly, we will characterize pulmonary and extrapulmonary replication and pathogenesis of MERS-CoV. Our Consortium of Coronavirus Research of the State Key Laboratory for Emerging Infectious Diseases has world-leading and budding coronavirologists, and the team leader is a member of the CoV Study Group of the International Committee on Taxonomy of Viruses, with excellent connections with coronavirologists internationally. Our laboratory is well-equipped with BSL3 animal facilities. The correct mix of critical mass of excellent researchers, available infrastructure and well established collaborations with researchers from the Middle East and China will allow us to break new grounds for MERS-CoV research. By identifying new intermediate viruses and hosts and new disease mechanisms, our studies will offer insights to prevention, diagnosis and treatment of MERS and future emerging CoVs.


Theme 1: Promoting Good Health
Project Title: Centre for Research into Circulating Fetal Nucleic Acids
Project Coordinator: Prof Dennis Yuk-ming LO (CUHK)

Abstract
Prenatal diagnosis is an integral part of obstetrics. Non-invasive prenatal testing based on circulating fetal DNA analysis has resulted in a paradigm shift in antenatal care. In 1997, the project coordinator first discovered the presence of cell-free fetal DNA in the circulation of pregnant women. In 2008, this research group was awarded funding for an Areas of Excellence (AoE) project (AoE/M-04/06). The funding enabled the team to make non-invasive DNA-based prenatal testing a clinical reality by developing a Down syndrome test that has subsequently been adopted in many countries. Another significant achievement was the non-invasive decoding of the fetal genome by maternal plasma DNA analysis. In the present proposal, we plan to bring together the same multidisciplinary team of pathologists, laboratory scientists, obstetricians, bioinformaticians and public health specialists, to solve the key unmet diagnostic needs in prenatal medicine. Specifically, we plan to develop the next generation tools for the analysis of cell-free nucleic acids and to study the biology and pathological characteristics of cellfree fetal nucleic acids that have not been unravelled to date. The novel tools and new biological insights will be directed towards the overall goal of developing approaches for the assessment of pregnancy-associated pathologies, such as single gene diseases, fetal demise and preeclampsia. The implications and benefits of non-invasive prenatal testing will be explored by an ethical, legal and social arm of our team. Knowledge and knowhow will be widely disseminated through training of postgraduate students and research personnel, as well as through educational workshops for the obstetrics and laboratory medicine professions.


Theme 2: Developing a Sustainable Environment
Project Title: Smart Urban Water Supply Systems (Smart UWSS)
Project Coordinator: Prof Mohamed S GHIDAOUI (HKUST)

Abstract
Urban water supply systems (UWSS) are the lifeline of 3 billion people globally; however, these vital systems are aging and fraught with deficiencies and inefficiencies. The World Bank estimates the monetary value of the lost water worldwide is about US$15 billion/year. Pipe failures can paralyze businesses and cause devastating urban floods. Worldwide, UWSS are challenged by urban growth and climate change. Yet current methods to diagnose leakages and defects in complex underground UWSS are highly inadequate.

Water infrastructure has been highlighted as a critical issue nationally-in the 2011 "No. 1 document" issued by the Chinese Central Government; in the 2011 "Green Quality Living in Greater Pearl River Delta" study; and in the 2008 "Total Water Management" and 2015 "Water Intelligent Network (WIN)" policies of the HK government. Indeed, HK has committed HK$23 billion to the rehabilitation and replacement of its water supply infrastructure. Many other countries are long overdue for massive UWSS upgrades (e.g., the American Water Works Association estimates that at least US$250 billion is needed in the USA alone).

The design and management of UWSS is currently limited by the range and resolution of data collection in the relatively inaccessible buried pipelines. Current methods fail to provide the diagnostic resolution needed for many practical problems. We propose a comprehensive theme-based research program involving theoretical, laboratory and field studies to develop a new diagnostic paradigm for water supply network monitoring and fault detection. We will study the sensing of actively generated waves that travel at high speeds (km/s) in the fluid in the pipe and to electronically capture wave echoes. The resulting data will be processed with advanced transient-based inverse methods and algorithms to pinpoint and characterize leaks, blockages and weak pipes. The theories will be evaluated in a field test bed in HK; a general pilot-scale demonstration experimental test bed will be developed for testing hydraulic transient behavior in UWSS.

We have assembled an internationally-recognized, cross-disciplinary research team to conduct the proposed research in close collaboration with the Water Supplies Department (WSD) of HK. The findings will enable timely detection of UWSS defects and proactive mitigation measures and will crucially contribute to the sustainable development of HK through water conservation.


Theme 2: Developing a Sustainable Environment
Project Title: Understanding Debris Flow Mechanisms and Mitigating Risks for a Sustainable Hong Kong
Project Coordinator: Prof Charles Wang-wai NG (HKUST)

Abstract
The risk of natural terrain landslides in Hong Kong is increasing due to urban encroachment on steep natural hillsides and more frequent extreme weather events. Disruptions caused by the landslides after the rainstorm on 7 June 2008, in particular debris flows, are vivid examples. In fact, the June 2008 rainstorm triggered many debris flows affecting developments including highways. The North Lantau Expressway, which is the sole vehicular access to the airport, was blocked by a debris flow for 16 hours. Unlike in many other regions, Hong Kong poses to engineers the challenges of heavy intensive rainfalls of over 2,000 mm per year, very steep slopes, densely populated areas and high land costs. All these challenges prevent the adoption of conventional and empirically based protective measures used in other parts of the world. A novel, safe and economical solution is urgently needed.

To reduce debris flow risks and to provide a safe and sustainable environment for economic growth in Hong Kong, a university-led industrial collaborative project will engage engineers, a computer scientist, an environmental scientist, an ecologist, and representatives from the Hong Kong Institution of Engineers.

This research project will adopt a holistic approach to tackle scientific challenges and to address the risk of debris flows in Hong Kong. It comprises of research studies in the following three inter-related key areas:

(a) Landslide material characterisation from micro to macro-scales and innovative monitoring techniques. The study aims to characterize typical Hong Kong debris flow materials at both particulate and continuum levels, from micro to macro-scales. A novel three-dimensional (3D) imaging system mounted on an unmanned aerial vehicle will be developed to capture high-resolution aerial images of inaccessible hillsides for establishing a terrain model for geomorphological appraisal and debris mobility assessment.

(b) Investigation of debris flow mechanisms. A state-of-the-art geotechnical centrifuge and a newly constructed large-scale in-situ flume using advanced instrumentation will be used in conjunction with a novel numerical model, which considers fluid-solid and solid-solid interactions, for simulations of debris flows. Field monitoring and physical model tests of debris flows will be conducted to provide data for calibration of the new debris flow numerical model.

(c) Risk mitigation measures. The use of multiple flexible barriers as a debris-resisting structure to mitigate the risk of debris flows will be studied for heavy rainfall and steep topography conditions in Hong Kong to validate the newly developed design guidelines.

The project will have an immediate impact on both local and international practice. It will lead to sustainable and proven mitigation measures, enhanced cost-effectiveness and more environmentally friendly maintenance and remediation works in Hong Kong and countries such as Canada, USA, Central and South Americas, Italy, Norway, the UK, and Malaysia, where debris flows are a constant threat. The scientific advancements and technologies from this project will also have impacts on the prevention and mitigation of snow avalanches and submarine landslides, mine tailing dams and food processing in which an improved fundamental understanding of particulate flows is also vital.


Theme 3: Enhancing Hong Kong's Strategic Position as a Regional and International Business Centre
Project Title: Safety, Reliability, and Disruption Management of High Speed Rail and Metro Systems
Project Coordinator: Prof Kwok-leung TSUI (CityU)

Abstract
Large network systems for electricity transmission, passenger transport, supply chain management, internet connectivity, finance and other applications may be increasing in complexity faster than we can ensure their safe, reliable and efficient operation. Monitoring technologies have developed just as rapidly, yielding large quantities of data. Massive challenges loom, however, in the synthesis of monitoring techniques with effective ways to mine the resulting data for information that can be acted on quickly and effectively.

Hong Kong has a reputation for innovation, dependability, efficiency and accountability in business services. Our proposal seeks to extend Hong Kong's advantages by establishing it as a center of expertise in the safety, reliability, and efficient management of complex network systems. We will focus specifically on high-speed rail (HSR) and urban (metro) train systems. It is anticipated that project results will be transportable to other complex network systems.

Our world-class team has expertise in the rapidly developing interconnected fields of remote sensing and monitoring, real-time probabilistic and statistical analysis of large,high-velocity data streams, and decision-theoretic techniques for economical operation of safe, reliable engineering systems. The proposed research is in two areas: ensuring the safety and reliability of HSR and metro engineering systems; and ensuring the safe and efficient management of passenger capacity, demand, scheduling and pricing. We will also prescribe decision processes for disaster management and rescheduling in the event of disruptions.

In the first area, engineering systems, we focus on safety and reliability of rails, wires and cables and locomotive components. We apply anomaly detection, failure discrimination, fault diagnostics and reliability degradation modeling to derive optimal maintenance schedules and supply chain management of critical components and spare parts. In the second area, people movement and capacity management, we will create strategies to forestall emergencies and respond to them when they occur. We will focus on fire safety, avoiding overcrowding scenarios, and optimal scheduling, pricing and revenue management. For post-disruption scenarios we focus on timetable adjustment and rolling stock and crew rescheduling.