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RGC Collaborative Research Fund - Layman Summaries of Projects Funded in 2014/2015 Exercise

Equipment Proposals

Four Dimensional Live Imaging of Zebrafish Embryos Development Using Light-sheet Microscopy and Biocomputational Tools
Project Coordinator: Prof CHENG Shuk Han (CityU)

The purpose of this equipment grant is to obtain from a matching fund from the Research Grants Council to purchase a light sheet microscope. This team of multi-disciplinary researchers has long been using the zebrafish embryo as a model organism to delineate important events in developmental biology and developmental toxicology. An individual cell in an embryo interacts with fellow cells and move around in the extracellular matrix. Only now, with the availability of the light sheet microscope, can we visualize and correlate the 3-dimensional (3D) tissue distribution of glycan with the 4-dimensional (4D) collective migration of cells. What we aim to achieve with this light sheet microscope, is to paint the 4D pictures of how aggregates of cells move in the 3-dimensional landscapes during the dynamic morphogenesis and organogenesis processes. This sort of information has been very difficult to obtain in the past due to the limitation of available microscopes.

Three-dimensional (3D) Atom Probe Facility for Characterization of Advanced Materials Research at Atomic- and Nano-scales
Project Coordinator: Prof LIU Chain-Tsuan (CityU)

It is well understood that material properties are determined essentially by characteristics at the atomic scale. To understand and ultimately control over the material properties, it is crucially important to quantitatively characterize the structural and compositional features at the atomic-scale spatial resolution. Among all types of nanoscale analytical tools available, atom probe tomography (APT) is the highest spatial resolution analytical technique. It offers extensive capabilities for both three-dimensional morphology imaging and chemical composition measurements at the atomic scale. Also, it is capable of quantitative detecting all elements including H, He, Li, C, and O with super-high sensitivity. It is anticipated that the APT facility will not only promote innovation and discovery in the fields of nanomaterials, nanotechnology, irradiation-induced damages, physics, chemistry, biomedicals, and electronics, but also provide tremendous opportunities for joint research between academic institutions and industries in Hong Kong and the near-by Pearl River Delta area.

Method Development by Using the Advanced Technique of NanoLC Coupled with NanoESI-LTQ Orbitrap Fusion MS and Applications for Proteomics and Metabolomics Researches
Project Coordinator: Prof CAI Zongwei (HKBU)

Mass spectrometry has played an increasingly important role in supporting various research projects including proteomics and metabolomics in Hong Kong. The analytical platform of combining proteomics and metabolomics has far-reaching implications in biological sciences including, but not limited to, human health and disease. Proteomics and metabolomics as the important parts of functional genomics provide whole pictures for understanding gene regulations, epigenetic changes and environmental influences. However, the intriguing mechanisms of these disorders or restorations need powerful analytical tools for supporting proteomic and metabolomics researches. This project intends to utilize our strong expertise in mass spectrometry to acquire an advanced instrument, namely nano-liquid chromatography coupled with nano-electrospray Orbitrap Fusion mass spectrometer, and develop methods for analyzing biomarkers of peptides/proteins and metabolites. The ultrahigh resolution Orbitrap Fusion mass spectrometry is very powerful for biomarker identification and quantification, particularly coupled with the ultrahigh performance liquid chromatography. Moreover, nano-liter LC could significantly improve the sensitivity and reduce the sample amount requirement. The obtained high sensitivity, high selectivity and broad dynamic range may guarantee the feasibility of quantitative analysis of compounds with diverse chemical structures in biological models of animals and cell lines for proteomics and metabolomics researches.

A Tier-2 Computing Center for Fundamental Physics
Project Coordinator: Prof CHU Ming-chung (CUHK)

The discovery of the Higgs Boson, or so-called 'God particle', in 2012, by the ATLAS and CMS experiments independently at the Large Hadron Collider (LHC) at CERN, highlighted many years of concerted efforts by scientists and engineers all over the world to achieve something rather miraculous: collisions of protons so energetic that the conditions roughly 10-12 s after the Big Bang are recreated in the laboratory. Each of these proton-proton collisions - 600 millions of them every second - can create thousands of particles that fly out in all directions and are recorded as electronic signals by the many layers of particle detectors. The huge amount of information generated at LHC - about 25 Petabytes of data annually - presents an unprecedented challenge for data sharing, storage, visualization and analysis. Since June 2014, the Hong Kong experimental particle physics team has become a full member of ATLAS, opening up exciting opportunities of new breakthroughs in fundamental physics to scientists and students from Hong Kong. We propose to set up a computing center in Hong Kong for ATLAS, which will be used for supporting simulation and analysis projects in astrophysics, cosmology, and particle physics. We will also develop technology based on erasure coding, which provides fault tolerance guarantees while reducing the redundancy overhead of replication.

A Unique-Multipurpose Transonic-to-Hypersonic Ludwieg Tube Facility for Study of the High-Speed Aerodynamics
Project Coordinator: Prof WEN Chih-yung (PolyU)

Hong Kong International Airport (HKIA) is currently the third busiest international passenger airport and the busiest international cargo facility in the world. The aviation industry associated with HKIA has directly contributed more than 5% GDP of Hong Kong. In view of the recent astonishing growth of the aviation industry in Asia Pacific, particularly China, The Hong Kong Special Administrative Region Government is building the third run-way at HKIA to secure her strategic role as the air transportation super hub in the world and to continuously expand her aviation industry. Meanwhile, China shows strong determination in developing her own commercial aircrafts and aerospace industry. To better link with the strong efforts of Hong Kong on the aviation industry and that of China on the aerospace research, education and research on aviation and aerospace engineering is critically important. Among all disciplines relevant to modern flying vehicles, high-speed aerodynamics is a fundamental and key knowledge because most vehicles are flying at transonic (commercial aircrafts), supersonic (fighters), and even hypersonic (rockets and space vehicles) speeds nowadays. Understanding the complicate high-speed aerodynamics relies on accurate wind tunnel experiments. Unfortunately, there is no high-speed wind tunnel in Hong Kong. Therefore, there is an urgent need to build a large-scale high-speed facility in Hong Kong for both research and educational purposes. This proposed project is motivated accordingly to offer a unique and multipurpose platform for promoting the inter-institutional research and education on the high-speed aerodynamics in Hong Kong. The primary objective of the project is to design, build and test a transonic-to-hypersonic Ludwieg tube with instrumentation and high-speed flow visualization systems. The other objectives are to conduct four multi-disciplinary collaborative researches with this equipment: (1) Experimental and numerical study of the supersonic/hypersonic boundary layer instability and the laminar-to-turbulence transition, (2) Experimental and numerical study of hypersonic rarefied flow around space vehicles, (3) Development and testing of new MEMS sensors to improve spatial resolution of measurements and functional meta-material structures to delay the boundary layer transition, and (4) Testing and examination of the transonic flows in the compressor blade cascade. It is envisaged that the proposed transonic-to-hypersonic Ludwieg tube will not only become one of the best facilities in the world for studying high-speed aerodynamics, but also enable the Hong Kong academia to be better prepared to support the high-speed aerodynamic research and education for the fast growing aviation and aerospace industry in Hong Kong and China.

A High-Output Protein Crystallography Facility with State-of-the-Art Area Detector and Automation Modules
Project Coordinator: Dr ZHAO Yanxiang (PolyU)

Protein crystallography is an essential technology of modern biomedical research. It enables scientists to obtain the three dimensional structures of protein molecules at atomic resolution and is crucial for structure-based mechanistic studies and drug discovery.

The current Protein Crystallography facility in PolyU has served as a highly productive technology platform since its establishment in 2006. Over 10 research labs from multiple Hong Kong tertiary educational institutes have used this facility to conduct cutting-edge research. Overall this facility has been essential for over 40 publications and over 20 competitively funded projects.

This project aims to upgrade the existing Protein Crystallography facility with new cutting-edge technologies including a state-of-the-art area detector for high quality data collection and automation modules to streamline the crystallization process. These upgrades would be crucial to enhance the capacity of the existing facility and to ensure that it will develop into an internationally competitive premier research centre.

Acquisition of an Ion Mobility Mass Spectrometer for Advancing Research in Drug Discovery
Project Coordinator: Dr YAO Zhongping (PolyU)

Ion mobility mass spectrometer is a new generation of mass spectrometer equipped with ion mobility technology. The ion mobility technology allows separation of ions based on their sizes and shapes and thus adds one more dimension of ion separation to conventional mass spectrometry, which only separates ions based on mass-to-charge ratios. Together with the features of high speed and high sensitivity, the proposed equipment allows acquisition of structural information of molecules effectively. In addition, the ion mobility technology significantly enhances the capability of mass spectrometry in analysis of complex samples and identification of compounds by reducing background interference, allowing separation of isomers, and providing additional information to reveal compound identity. These advantages significantly facilitate and open new possibilities to many research areas including drug discovery.

The Department of Applied Biology and Chemical Technology of the Hong Kong Polytechnic University has research strength in drug discovery, and is devoted to collaborate with other institutes to conduct world-class research in drug discovery. The drug discovery research involves a lot of structure-related studies and analysis of complex samples. In order to cope with the increasingly challenges in this field, the purchase of the proposed ion mobility mass spectrometer, which has superior capability in structural studies and analysis of complex samples, is essential. It would significantly promote the development of drug discovery and enable the setup of a platform for collaboration among different institutions in Hong Kong.

Super-resolution Electron Microscopy Facility for Cross-disciplinary Materials Research
Project Coordinator: Prof WANG Ning (HKUST)

The increasing intensity of research carried out in Hong Kong has meant a continuously growing demand for better structural characterization capabilities for advanced and nano-sized engineering materials. Transmission electron microscopy (TEM) offers the highest resolution for imaging material structures among all kinds of microscopic approaches. The spherical aberration correction technology overcomes the fundamental optical limitations of magnetic lenses and enables the use of TEM to explore atomic structures of materials with sub-Angstrom resolution. The super-resolution TEM facility we proposed is based on the aberration correction technology. This facility will restore our electron microscopy facility to the global standard and promote cross-disciplinary collaborations, particularly for the research in materials science and engineering, applied physics, mechanical and civil engineering, chemistry and chemical engineering, micro/nano-electronics and biomaterials. The research areas to be benefited include engineering metal/alloy materials, nano-composite materials to energy-related materials, nano-electronic devices to functional bio-nanomaterials, etc. In the long term, this new facility will dramatically improve our ability to carry out state-of-the-art research involving structure characterization of materials and provide great opportunities for professional training and education of science and engineering students.

Two-photon light sheet microscope system for deep and fast live imaging
Project Coordinator: Prof LOY Michael M T (HKUST)

This major equipment purchase will allow us to construct a Two-Photon Light Sheet Microscope (TPLSM) for in vivo, fast, 3-D imaging of large biological samples. Truong et al (Nature Methods, 9, 757 (2011)) demonstrated that combining two-photon excitation and scanned light sheet achieving both high imaging depth into biological samples and high imaging speed (>70 frames s-1) without compromising normal biology due to effects of phototoxicity. This is not possible with any other instruments. The addition of this 'deep and fast live imaging' capability will nicely complement our existing STORM super-resolution capability of imaging at sub-20nm resolution but at rate of several minutes per frame or longer.

This microscope will allow researchers in Hong Kong to perform 3D live fluorescence imaging of living cells or tissues up to 500 m deep, at 200 images/sec, for many hours. With this instrument, biologists and medical researchers will be able to view and study living systems in all their dynamic complexity in real time at video speed.

Micro-PET for pre-clinical molecular imaging research in Hong Kong
Project Coordinator: Prof KHONG Pek Lan (HKU)

The objectives are to establish a research platform in pre-clinical molecular imaging that will be unique to Hong Kong, facilitate multi-disciplinary and multi-institutional research in translational imaging especially in the research area of cancer, and also cardiovascular and neurodegenerative diseases. Molecular imaging of a living animal can provide important information on how its body is functioning by allowing the non-invasive 'visualisation' of molecules and molecular events in cells and tissue. These functions can be studied using organic molecules and pharmaceuticals labeled with positron-emitting radionuclides (or tracers) produced by a cyclotron, and detected by a positron-emission tomography (PET) scan. These probes provide valuable insights into biochemical, physiological, pathological and pharmacological processes in the cells and tissues. It is powerful especially for the diagnosis and assessment of cancer in helping answer questions regarding the mechanism of cancer cell suppression, proliferation and spread, the effectiveness of targeted treatment etc. The small animal PET scan (microPET) is key in allowing research studies to be first conducted in animals models of human disease before it is translated to clinical practice.

Establishment of a shared live cell imaging platform for super-resolution microscopy
Project Coordinator: Prof TSAO George Sai Wah (HKU)

Fluorescent imaging microscopy is an essential tool for life science and biomedical research and have wide research applications on cancer, stem cell, neuroscience, healthy aging, infectious diseases, immunology, bio-medical engineering and many other fields of investigation. Due to the diffraction property of light, the highest resolution power of confocal microscope under optimal condition is ~250 nanometer. However, many cell biological events at subcellular levels, including cytoskeleton dynamics, DNA-protein interaction, viral entry, organelle organization, vesicle trafficking, and endocytosis cannot be well-resolved by conventional microscopy. It is necessary and important to develop and strengthen advanced microscope techniques to tackle new challenges in molecular and cell biology.

Super-resolution fluorescence imaging microscopy is a powerful research tool to overcome the resolution limit. With the integration of new optics, fluorescent probe, high quantum efficiency imaging detector, and image reconstruction technology, various new imaging methodologies have been developed to improve the resolution power in recent years. For example, Structural Illumination Microscopy (SIM), Stochastic Optical Reconstruction Microscopy (STORM), and Stimulated Emission Depletion microscopy (STED) have been implemented to achieve higher resolution (20-120 nanometers). Three-dimensional and multicolor super-resolution imaging also allows direct subcellular localization and interaction of biomolecules at subcellular and even at single molecular level.

The combination of super-resolution microscopy and live cell imaging is particularly powerful and is a rapidly advancing field in biomedical research. Rather than observing fixed samples, live-cell super-resolution microscopy enables us to study signal transduction and molecular interaction in a time-dependent manner. This unprecedented imaging power has enabled researchers to directly visualize subcellular and molecular events in living cells at nanometer scale and has revolutionized many old concepts in biomedical sciences and to re-define many unsolved questions.

In Hong Kong, super-resolution microscopy is relatively underdeveloped compared to many leading research institutes oversea. For Hong Kong to remain competitive in life science and biomedical research, it is timely to promote and develop super-resolution fluorescent microscopy. The core facility in HKU Faculty of Medicine is a user-based shared facility and will be well fitted to initiate the advanced imaging platform in Hong Kong. The establishment of live cell super-resolution imaging microscopy will greatly enhance the research competitiveness of our researchers in Hong Kong enabling them to make important contributions to the advancement of biomedical sciences.

Inert-Environment Facilities for investigating optical-electrical-thermal properties of hybrid structure optoelectronics
Project Coordinator: Dr. CHOY Wallace Chik Ho (HKU)

Through establishing the unique inert-environment facilities in Hong Kong, our objectives are to address challenges of hybrid material based optoelectronic devices including (1) light management in the devices, (2) efficient carrier transport between active layer and electrode, (3) hybrid material systems for flexible electrodes, (4) thermal management of the hybrid structures, and (5) comprehensive understanding of device physics. We would also like to promote collaborative research among professionals with multidisciplines from institutions and industries.

The proposed system covers aspects ranging from fabrication of optoelectronics devices to characterization of optical/ electrical/ thermal properties of materials and devices including:
(1) fabrication of multi-layered and bulk thin film structures of hybrid material system, (2) transient and static optical/ electrical/ thermal properties characterization, (3) morphologies and nanoscale electrical properties characterization, and (4) thermo-scanning microscopy and thermal imaging.

Group Research Proposals

EXPO and Autophagosome in Plants
Project Coordinator: Prof JIANG Liwen (CUHK)

The goal of this project is to understand the underlying mechanisms of the E2-exocyst complex recruitment and function in plants as well as the functional relationship between EXPO and autophagosome during autophagy in plants. Since both EXPO and autophagosome play important roles in regulating plant growth and development as well as plant response to environment, our studies will contribute greatly towards our understanding about organelle biogenesis and function in plants.

Elucidating the molecular defects associated with PTEN mutations in Autism Spectrum Disorders
Project Coordinator: Prof CHAN Man Lok Andrew (CUHK)

Autism Spectrum Disorders (ASD) are a collection of neurocognitive deficits affecting an estimated 26.6 per 10,000 individuals in Hong Kong. It has an early onset of 3 year of age and is characterized by the lack of social interaction and language skills. Patients are care for by a multidisciplinary team of medical professionals with behavioral therapies being the main treatment modality. While environmental factors may play a role, the major cause of ASD has a strong genetic component. This proposal will study an ASD susceptibility gene, PTEN, which is mutated in 1% of ASD. PTEN suppresses protein synthesis and the loss of PTEN is expected to cause aberrant accumulation of proteins in ASD brains. The pathological consequence is the dysregulation of normal nerve signal transmission. This proposal aims to achieve three goals. First, a panel of PTEN mutations found in ASD patients will be characterized. Hong Kong-based cases will be included to strengthen local resources of ASD research. Second, the aberrant proteins produced in ASD neurons lacking PTEN will be identified. They may be targets for future drug development in treating this disorder. Finally, a novel mouse strain with part of PTEN implicated in nerve signal transmission missing will be characterized. The long-term goal is to understand how specific gene mutations can link to specific clinical features of ASD. This proposal represents a highly focused study to dissect the genetic basis of ASD and will deepen our understanding of this complex disease.

Functional Liver Cancer Epigenomics: Exploiting Epigenetic Vulnerabilities for Therapeutics
Project Coordinator: Prof CHENG Alfred Sze-Lok (CUHK)

DNA and histones are targets of multiple modifications that convey flexibility to the genome. However, these epigenetic events are often hijacked in carcinogenesis. While chronic hepatitis B remains the major etiology of hepatocellular carcinoma (HCC), the growing epidemic of obesity which leads to non-alcoholic fatty liver disease has emerged as an important risk factor. The rapidly accumulating evidence that epigenetics converts inflammatory and over-nutrient microenvironment into aberrant transcriptional activity thus underscores the fundamental roles of epigenetic regulation in HCC pathogenesis. We have hence assembled in this application a dedicated multi-disciplinary group of researchers to continue our synergistic interactions in the pursuit of epigenetic vulnerabilities in HCC. Through seamless integration of the complementary epigenome, genome and transcriptome information, the long-term goal of our efforts is to derive the next generation of effective targeted therapeutics to reverse transcriptional abnormalities that are inherent to the HCC epigenome.

Joint R&D of Biometals as Orthopaedic Implants
Project Coordinator: Prof QIN Ling (CUHK)

Trauma-, sports- and age-related musculoskeletal injuries impose huge medical and socioeconomic burdens to our patients, families and society globally. The needs for medical device and implants are rapidly increasing, especially in our aging society and society with fast development of traffics and sports. Conventional orthopaedic implants developed for fixation of bone fracture and tendon/ligament-bone insertion (TBI) are made of permanent metals such as stainless steel and titanium (Ti) that are too rigid for fixation that may impose unfavorable effects, such as stress shielding to the healing tissues and impair the nature healing process. Second operation for implant removal is often needed that may also consequently weaken the bone or TBI structure and often result in refracture. To develop biometals that stable at initial fixation phase and then gradually degrade with healing over time are highly desirable, especially for those biometals that their degraded ions have no safety concerns yet capable of stimulating healing tissues for earlier and faster healing as this is practically important for avoiding delayed or non-union of injured tissues and even more attractive for avoiding second or removal operations attributed to their in vivo degradation properties. Pure magnesium (Mg) or its alloys are such promising candidate biometal that our multi-disciplinary team has been working on with or without innovative surface coating for various desirable indications in clinical orthopaedics.

Our application will synergize our expertise from metallurgic engineers, biomaterial scientists, preclinical and clinical scientists and orthopaedic surgeons to enhance our multidisciplinary collaborations among our UGC-funded institutions in joint R&D of highly promising biometals for wide orthopaedic applications and will generate significant academic output in terms of quality publications and patents or knowledge transfer on top of our strength and track records in individual disciplines and translational orthopaedics. Our joint research and development (R&D) and translational efforts will provide clinical applicable Mg-based orthopaedic implants to be registered and tested for clinical applications. Our interinstitutional collaborations with international support will strengthen this highly promising R&D in medical implants that will revolutionize our orthopaedic clinical practice, including avoiding second implant removal surgery. In turn, our collaborative efforts will facilitate significant reduction in medical costs and release global socioeconomic burdens for our patients, families and governments.

Non-planar Polycyclic Arenes: From Molecules to Materials
Project Coordinator: Prof MIAO Qian (CUHK)

Non-planar polycyclic arenes are unique objects of structural organic chemistry, and play an important role in science of carbon nanomaterials. They have recently received considerable attention in the fields of supramolecular chemistry and organic functional materials because of their interesting properties and promising applications. Many non-planar polycyclic arenes remain challenging targets of organic synthesis because they typically involve intrinsic strains. Lack of efficient synthesis has impeded the applications of non-planar polycyclic arenes as functional materials, such as organic semiconductors in electronic devices. To meet the challenges in synthesis of non-planar polycyclic arenes and to explore these structurally unique molecules for applications as novel functional materials, we propose here a collaborative research project by combining interdisciplinary expertise of organic synthesis, supramolecular chemistry, computational chemistry, carbon nanomaterials and electronic device engineering.

On the basis of our previous work on non-planar polycyclic arenes, we have designed three groups of molecules for this project: (1) twisted polycyclic arenes as organic semiconductors, (2) polycyclic arenes containing seven-membered carbocycles, and (3) polycyclic arenes containing eight-membered carbocycles. Research on these structurally unique molecules is planned to cover four aspects: (1) establishment of efficient synthesis; (2) development of novel supramolecular structures for organic semiconductors as well as liquid crystals; (3) fabrication and characterization of organic electronic devices; and (4) computational and experimental study of novel carbon nano-structures that can in principle be grown from the non-planar polycyclic arenes.

Organic semiconductors are key components in flexible and low-cost organic electronic devices, which are of great fundamental interests in materials science and are also recognized as a growing market for industry. Organic semiconductors based on non-planar polycyclic arenes may have novel molecular packing and functions that are often unavailable for planar organic semiconductor molecules. With non-planar organic semiconductors, this proposal aims to address two important issues in the research of organic semiconductor materials and devices, namely, the molecular packing of organic semiconductors for high-performance organic thin film transistors (OTFTs), and supramolecular assemblies in the p-n heterojunction of organic photovoltaic solar cells (OPVs).

The success of this proposed study could result in efficient synthetic methods for non-planar polycyclic arenes and new design strategies for carbon-rich materials, and may open a new avenue to OTFTs and OPVs with better performance. A comparison of the non-planar polycyclic arenes with their planar analogues will lead to interesting findings on the structure-property relationship.

Marine Genomics: Crustacean Evolution and Aquaculture
Project Coordinator: Prof CHU Ka-hou (CUHK)

Shrimps, crabs, lobsters and crayfishes all belong to a group of animals named as the crustaceans. They are found worldwide and are of great scientific interests as well as commercial importance in fisheries and aquaculture. Together with other joint-legged animals such as insects, they form the majority of animal species in the world. In this project, we aim to sequence the genomes and obtain the transcriptomes of different life stages from eight key crustacean species for better understanding of animal evolution and advancement of aquacultural biotechnology.

Development of Design Methodologies for the Improvement of Wind and Thermal Comfort in the Urban Environment
Project Coordinator: Prof MAK Cheuk-ming (PolyU)

Wind speed and thermal comfort conditions, especially in high-density cities, can be adversely affected by moderated local airflow field and solar radiation captured by building arrays. The air ventilation assessment (AVA) scheme currently in place in Hong Kong uses a velocity ratio (VR), defined as pedestrian level wind velocity to the higher level unobstructed wind velocity, to assess the impact of new estate developments on urban ventilation but offers little guidance to evaluate the design options. More recently the concept of city ventilation was advocated to establish correlations between macro-scale urban porosity and the city scale air change rate. There is a lack of and therefore a need for feasible engineering and design solutions to address this urban heat island (UHI) problem. This research aims to develop a modeling-based design methodology to improve wind and thermal comfort conditions at the pedestrian level in communal areas within a neighborhood or a housing estate, while the average community-scale temperature and wind are subject to UHI effects determined by macro-scale landscape and city morphology.

State-of-the-art wind tunnel technique will be used to obtain bench-marking data of airflows around a building block with several novel architectural features. These data will be used to validate and develop turbulence models for numerical simulation of the airflows. On-site measurements will be conducted to obtain the real life urban environmental parameters including temperature, humidity, solar radiation, ground surface radiation and wind speed, and these will be used to develop the seasonal adaptive, human physiology based thermal comfort models. The new knowledge on airflow, solar radiation, and human body thermal comfort modeling will all be integrated into one comprehensive computational platform, so that the combined effects of building deposition, orientation, forms and heights, façade aperture, and ground and wall surface materials on the thermal comfort conditions at any particular points can be rigorously assessed hour-by-hour for a year-round period. Through such a rigorous simulation analysis, it is expected that the outdoor thermal comfort can be achieved in selected time slots of a day, when city residents wish to enjoy some outdoor activities and in the intended area over a prolonged period in a year.

The project is conceived to capitalize on the increased computing power available and a wide spectrum of physical and numerical modeling expertise of the project team members. The long-term benefit of the project outcome is improved urban environmental quality, livability and public health in large cities.

Heterogeneous Chemistry of Atmospheric Reactive Nitrogen Oxides: An Integrative Programme for Cutting-edge Science
Project Coordinator: Prof WANG Tao (PolyU)

Reactive nitrogen (N) compounds are a family of N-containing compounds in a chemically active (oxidized) form. They play key roles in atmospheric chemistry, soil and water pollution, and biodiversity. Some nitrogen oxides are in fact the driving force of the current severe roadside air pollution and smog/haze problems in Hong Kong. While mostly emitted in the form of NO, the atmosphere converts it into many oxidized forms, with many processes occurring not only homogeneously but also at the air-particle interfaces (heterogeneous process). Due to their importance, these transformations have been the focus of intensive research; nevertheless recent findings highlighted the fact that our understanding is still sparse for the heterogeneous part, due to the challenges in studying complex processes at air-particle interface for which more sophisticated research tools are required. However, it is critically important to understand via which reaction pathways the chemical transformation occurs so as to accurately predict and mitigate their environmental impact.

This project aims to develop an integrative framework, by uniting the expertise in the laboratory, field, and numerical simulations, and to conduct cutting-edge research on fundamental chemistry of reactive nitrogen, focusing on heterogeneous processes/sources of HONO and N2O5-which is a topic of intense on-going international research, due to the major importance of these compounds in air pollution. The outcomes of this project will include (1) new knowledge of the chemistry of the polluted atmosphere in coastal regions with strong interactions of man-made and oceanic gases and particles (2) new research tools suitable for Hong Kong, the Pearl River delta and other similar regions (3) a report to the government on findings which will support mitigation of roadside and haze pollution in Hong Kong and other Chinese cities.

Ligand-Enabled Direct and Regioselective C-O bond Cleavage/Functionalization of Aromatic and Aliphatic Ethers for Sustainable Chemical Syntheses
Project Coordinator: Prof KWONG Fuk Yee (PolyU)

Direct assemble of versatile organic molecules for pharmaceutical and material applications are the fundamental subjects to make a new horizon of chemical science. Indeed, the establishment of a simple tool to cut the chemical bond selectively and effectively is the major challenge for sustainable synthesis. This project integrates multi-institutional and multi-disciplinary efforts from The Hong Kong Polytechnic University, The University of Science and Technology and The Chinese University of Hong Kong, and the complementary expertise of synthetic chemists, material and theoretical scientists, for building a team in tackling the grand challenge related to green chemistry. It is envisaged that the success of rational catalyst design and development would lead to effective chemical synthesis from rich natural feedstock biomass and thus promote Hong Kong towards a low carbon economy.

The Role of IL-33 in Synaptic Dysfunctions and Pathogenesis of Alzheimer's Disease
Project Coordinator: Prof IP Nancy Y. (HKUST)

Alzheimer's disease is an irreversible degenerative brain disease and a leading cause of death in the elderly. The disease is characterized by deposits of extracellular £]-amyloid (A£]) plaques and excess intracellular accumulation of tau protein (neurofibrillary tangles), and patients exhibit a progressive decline in memory, reasoning, judgment, and movement abilities. Despite the large number of people with Alzheimer's disease, there are presently no cures while existing treatments only offer short-term symptomatic relief. Disease-modifying treatments are under development but the primary obstacle in developing effective therapies is the lack of knowledge of the physiological mechanism of the disease. In recent years, Alzheimer's disease has been viewed as a multi-systems disorder rather than purely a brain disease, and studies have implicated the immune system in disease pathology. Thus, in this project, we aim to determine how inflammation contributes to Alzheimer's disease, by focusing on the cytokine interleukin-33 (IL-33). IL-33 and other interleukins are important components of the immune system and play critical roles in immune responses. We will investigate the involvement of IL-33 and its signaling pathway in various mouse models of Alzheimer's disease (representing different stages of the disease). In particular, the beneficial effects of IL-33 on cognitive abilities such as learning and memory as well as the pathology of Alzheimer's disease will be investigated. These findings will help evaluate whether IL-33 can be used to treat Alzheimer's disease as well as mild cognitive impairment, an early stage of dementia that precedes Alzheimer's disease. Furthermore, studies will be conducted to elucidate the cellular mechanisms underlying the function of IL-33 in Alzheimer's disease. The results will enhance our understanding of the immune system (including the cytokine network) dysfunctions in Alzheimer's disease. By understanding the inflammation pathway driving disease progression, we will also aim to uncover new molecular targets which will aid in drug development efforts. This project is a significant initiative, and the findings will greatly contribute to current understanding of Alzheimer's disease as well as the collective global movement to help find an effective cure. The project will also highlight the high-level of research work being undertaken in Hong Kong, and thus help elevate Hong Kong's status as a center for advanced molecular neuroscience research, which in turn contributes to the growing local biopharmaceutical industry and knowledge-based economy.

Dynamics of Soft Matter at Interfaces: Theory, simulations and experiments
Project Coordinator: Prof TONG Penger (HKUST)

Among the different disciplines of physics, soft matter has the distinction that its research topics involve a preponderance of phenomena that occur in our daily lives. The subject matter of this proposal, dynamics of soft matter at interfaces, is no exception. We target as two of our objectives the detailed understanding of dynamics at the triple-phase intersection of a solid surface with two immiscible fluids, i.e., the moving contact line that can occur in drinking coffee, for example, and the characterization of the fluid-fluid interfacial dynamics which underlies the formation of many commercial products such as cosmetics, food additives, and drugs. A third objective involves the study of the surface melting dynamics of solid from direct observations on a unique colloidal system in which the particles can have tunable attractive interactions. While the relevant background phenomena of our proposal are fairly ubiquitous, their study is scientifically challenging and demands a collaborative team that crosses disciplinary boundaries between physics, mathematics, and materials science and between theory, simulation, and experimentation. We have assembled such a team.

Our research team consists of four experimentalists and three theorists and approximately 40 research associates including postgraduate students and postdocs from the disciplines of physics, applied math, and mechanical engineering in the three major research universities in Hong Kong. A very good working relationship has already been established, owing to our common interest in understanding liquid-liquid and fluid-solid interfacial phenomena. The successful completion of this project would provide information and knowledge useful for a variety of potential applications ranging from improved prediction of multiphase permeability in porous media, tertiary oil recovery, green chemical processing using water-based products in microfluidics, to improved material processing through a detailed knowledge of surface pre-melting dynamics. Furthermore, students at both the postgraduate and undergraduate levels and postdocs participating in this project will receive broad training in interdisciplinary research, which will prepare them for a wide range of careers in academia and industry.

Elucidation of the role of Pax7 in muscle stem cells
Project Coordinator: Prof WU Zhenguo (HKUST)

Adult muscle stem cells (MuSC) are responsible for muscle regeneration in response to various forms of muscle injury. In uninjured adult muscles, MuSC are physically located outside of individual muscle fibers and exist in a "dormant" state (also called "quiescent state"). Pax7 is a key regulator of MuSC, as loss of Pax7 resulted in depletion of MuSC in Pax7 mutant mice. However, it remains largely unclear how Pax7 functions to regulate MuSC. In this proposal, we aim to study the roles of Pax7 in MuSC in three aspects: (1) how Pax7 promotes the expansion of MuSC upon muscle injury; (2) how Pax7 maintains the identity of MuSC by suppressing an alternative cell fate (i.e., brown adipocytes); (3) how Pax7 regulates the "quiescent state". The knowledge gained from our study will provide important insights into stem cell functions in the context of tissue regeneration, disease and aging. As dysregulation of MuSC also contributes to the pathologies of a number of muscle diseases including the fatal Duchenne muscular dystrophy, a thorough understanding of the molecular mechanisms that regulate MuSC will provide valuable information for designing effective therapies in the future.

Total Municipal Organic Waste Management by integrating Food Waste Disposal And Sewage Treatment (MOW-FAST)
Project Coordinator: Prof CHEN Guanghao (HKUST)

Solid waste is one of the most challenging environmental issues in Hong Kong. Food waste accounts for 36% of the municipal solid waste (MSW), contributes to difficult odor control and expensive leachate treatment, and significantly undermines the current landfill disposal practice. It also reduces the heat value of MSW dramatically when it is to be incinerated in the near future. Source separation of food waste for energy recovery is regarded as an ideal solution. However, it is extremely difficult to practice with domestic food waste (DFW). A Food Waste Disposer (FWD) is thus proposed to transfer it from kitchens to sewerage systems for energy recover via bio-gas production from separate or co-digestion of DFW with sludge. The entire process is named "Total Municipal Organic Waste Management by integrating Food Waste Disposal And Sewage Treatment (MOW-FAST)". By leveraging mature FWD technology, the modern sewerage system, and an advanced sewage treatment process, the feasibility of the MOW-FAST system is high. However, its impacts on the local sewerage systems are not known due to the unique conditions in Hong Kong, including the dietary and cooking habits of local residents, the saline sewage resulting from seawater toilet flushing and the high temperature / warm climate, which are very different from those in western cities currently practicing FWD. Hence, the potential impacts of the MOW-FAST system on the sewers, existing wastewater treatment processes, anaerobic sludge digestion, and its engineering feasibility and economic analysis will be extensively studied through the following five major tasks.

1) Characterization of domestic food waste (DFW), FWD effluent, and the mixture of FWD and wastewater;
2) Laboratory study and model-based valuation of the impacts of FWD on the sewer system;
3) Model-based evaluation of the impact of FWD on biological wastewater treatment;
4) Laboratory study and model-based evaluation of the impacts of FWD on anaerobic digestion; and
5) Engineering feasibility and economic analysis of the MOW-FAST system.

This project will offer a new solution to minimize DFW efficiently and effectively as well as recover energy from such waste in Hong Kong.

A Multidisciplinary Study on CD133 Liver Cancer Stem Cells: Molecular Mechanisms, Clinical Relevance and Therapeutic Implications
Project Coordinator: Dr. MA Stephanie Kwai Yee (HKU)

Cancer is hierarchically organized and composed of a heterogeneous population of cells, among which researchers have now provided solid evidence of the existence and importance of a cancer stem cell (CSC) compartment. This fraction of tumor cells shares many similarities with normal stem cells, such as self-renewing capacity and multi-lineage differentiation properties. In addition, CSCs are also highly tumorigenic. The discovery of the role of CSCs has altered the landscape of cancer research. From a clinical point of view, the main concern with CSCs is their resistance to conventional treatments like radiation and chemotherapy, a feature that has now been extensively shown to be an underlying cause of tumor recurrence. This would require that we rethink the way we diagnose and treat tumors, as in addition to eliminating the bulk rapidly dividing cells that are the current targets of treatment, we will also have to focus on targeting the CSC subpopulation that fuels tumor growth. In light of this, there is a need to define the factors that sustain CSCs in order to develop more efficient therapies. There is now ample evidence to show that, like many other solid tumors, a CSC subpopulation does also exist in the locally prevalent cancer type Hepatocellular Carcinoma (HCC). We and others have previously identified a specific subset of liver CSCs that is marked by their CD133 surface phenotype and bearing features that include the ability to self-renew, differentiate, initiate tumors in vivo and resist chemotherapy. Further to its role as a liver CSC marker, we also found CD133 to play a functional role in regulating tumorigenesis of liver CSCs through CD133 shRNA knockdown assays. However, the exact mechanisms that govern CD133+ CSCs in HCC remain largely unexplored. Based on the hypothesis that CD133+ liver CSCs is vital in fueling HCC growth and recurrence, in this project, we seek support to characterize the molecular mechanisms underlying CD133+ liver CSC initiation, maintenance, progression and differentiation via multiple perspectives (viral associated, genes/pathways, comparison of CD133 subsets from normal/non-tumor and HCC). The importance of what can be achieved cannot be overemphasized because of the high incidence and mortality of HCC in the local community and beyond.

Novel Structure and Function of Human Sirtuins
Project Coordinator: Prof HAO Quan (HKU)

Human Sirtuin family proteins are involved in the regulation of various biological processes. Malfunction of Sirtuins have been implicated in many human diseases including aging, cancer, metabolic diseases and neurodegenerative diseases. Understanding the molecular structures and functions of the Sirtuins is very important for better characterization of their biological role and drug design. This proposal aims to determine the crystal structures of a number of Sirtuins to investigate the structure-guided functions, to use chemical probes to identify Sirtuin substrates, and to design novel Sirtuin inhibitors for use in research or medicine.

Investigation of effects and molecular mechanisms of FGFR2-positive cancer-associate fibroblasts on tumor microenvironment in esophageal squamous cell carcinoma
Project Coordinator: Prof Guan Xin-yuan (HKU)

A malignant tumor is composed of cancer cells and non cancer cells such as immune cells, endothelial cells and fibroblasts. These non cancer cells, within or surrounding tumor tissue, compose tumor microenvironment (TME), which plays a very important role in cancer development and progression by providing structural and supportive framework, promoting cell growth and metastases. Cancer-associated fibroblast (CAF) is one of the important components of TME. Although the role of CAFs in cancer progression has been widely studied, the molecular mechanism of CAFs recruitment and their cross-talk with cancer cells are unclear. Our recent study finds that CAFs in esophageal squamous cell carcinoma (ESCC) are FGFR2-positive cells, which can provide cancer cells with a suitable microenvironment by promoting cell proliferation, inducing angiogenesis and promoting metastasis. Characterization of the origin of CAFs and their recruitment, as well as their interaction with cancer cells will greatly facilitate our knowledge of the molecular basis for ESCC development and progression. As FGFR2 is a unique cell surface marker for CAFs in ESCC, it provides us a very useful tool to study above mentioned questions. In this project, three objectives will be addressed in order to answer following scientific questions: 1) where and how FGFR2+ CAFs are recruited; 2) how circulating FGFR2+ fibrocytes differentiate from FGFR2+ CAFs in tumor tissue; 3) what is the effect of FGFR2+ CAFs on ESCC phenotype, especially on cancer stemness; and 4) whether FGFR2+ CAFs can be potential therapeutic targeted? Several "state of the art" techniques including high-throughput sequence and gender-mismatched bone marrow transplantation will be applied to address these questions. Two approaches will be applied to test the potential therapeutic value by targeting FGFR2+ CAFs. Anti-FGFR2 and anti-Wnt2 antibodies will be used to block the recruitment of FGFR2+ CAFs and to neutralize Wnt2 protein secreted by FGFR2+ CAFs. Immune surveillance plays key roles in preventing and eliminating tumor cells. To avoid being attacked, tumor cells can express inhibitory ligands on their surface to inhibit cytotoxic T cell function through interaction with T cell receptors such PD-1. Recently, we identify an alternatively spliced isoform of PD1, named £G42PD1, which can inhibit cytotoxic T cell function through interaction with TLR4. Interestingly, our preliminary work demonstrates that TLR4 can be detected in FGFR2+ CAFs in ESCC, suggesting that FGFR2+ CAFs may inhibit activated T cells and NKT cells via £G42PD1/TLR4 interaction. This hypothesis will be also addressed in this project. The successful completion of this project will explore how cancer cells interact with other cells to build a suitable microenvironment. It may lead to the development of novel therapeutic agents for blocking the recruitment and oncogenic function of FGFR2+ CAFs in ESCC.

Fe-enhanced primary sedimentation and sludge acidogenesis for resources (P and PHA) recovery during wastewater treatment
Project Coordinator: Prof LI Xiao-yan (HKU)

Water is one of the most important natural resources on earth. However, many forms of development cause water pollution, which can greatly deteriorate the quality of life and threaten the public health, as evidenced in Hong Kong, mainland China and many other regions. Current municipal wastewater treatment systems rely on the core technologies that were developed more than half century ago and are no longer capable of accommodating the situations of fast population growth, urbanization and industrialization in many areas of the world. Major pollutants in wastewater, such as phosphorous (P) and organics, are also valuable materials. However, recovery of such resource materials is often hindered by their low concentrations in wastewater. The proposed development is to utilize ferric iron-enhanced primary sedimentation to concentrate pollutants (organic and P) into sludge, which also will reduce the pollutant load on the downstream treatment process. An anaerobic reactor is proposed for the sludge hydrolysis and acidogenesis that transforms the settled organic to volatile fatty acids (VFAs) and releases phosphate into the liquid phase. The phosphate can be recovered by precipitation to become P-fertilizer, and the VFAs-rich sludge liquor will be used for biosynthesis of polyhydroxyalkanoates (PHAs) as a value-added bioplastic product.

The novel process can be readily modularized and adopted as simple add-on units to upgrade existing municipal wastewater treatment systems. The new development will improve the pollutant removal efficiency, reduce the overall energy consumption of wastewater treatment, and allow effective resource recovery. Besides the scientific merits contributing to water pollution control technologies, the new process can be applied to the upgrading of chemically enhanced primary treatment (CEPT) currently used in Hong Kong to the level of secondary biological treatment. Pilot-scale experiments will be conducted in the late phase of the project to demonstrate the technological breakthrough, cost-effectiveness and long-term benefits of the new process for a more sustainable wastewater treatment and waste-to-resource operation.

A Multi-disciplinary Approach to Investigate Vascular Dysfunction in Obesity and Diabetes: From Molecular Mechanism to Therapeutic Intervention
Project Coordinator: Prof XU Aimin (HKU)

Cardiovascular diseases (CVDs), including stroke, heart attack and periphery artery disease, are the major cause of death and hospitalization worldwide. The increasing incidence of CVDs is attributed to the rapid rise in the prevalence of obesity and diabetes. Despite recent research advances in this field, the current drug therapies are far less optimal to control these chronic diseases. To develop more effective strategies for prevention of fatal CVDs, it is of utmost importance to elucidate the detailed pathological pathways that link obesity, diabetes and CVDs. With the support from our previous Collaborative Research Fund, we have identified several fat-derived circulating factors and microRNAs as a key mediator of obesity-related CVDs in mice. The aims of this study are to validate the potentials of using these circulating factors as a biomarker for early diagnosis and a therapeutic target for early intervention in large animals and humans, to comprehensively investigate the pathological roles and clinical relevance of these circulating factors in the development of CVDs, and to elucidate the detailed molecular pathways by which these novel factors in mediating obesity-associated vascular inflammation and atherosclerosis. This project will enable us to consolidate and expand our platforms to support basic, translational and clinical research on obesity, diabetes and CVDs in Hong Kong.