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.
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.
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.
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.
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.