The First Integrated cryo-EM and cryo-ET Shared Facility for Life Sciences Research in Hong Kong
Project Coordinator: Professor JIANG Liwen (CUHK)
Electron cryomicroscopy (cryo-EM) has emerged as a powerful tool for seeing the threedimensional (3D) structures of biological molecules at high resolution due to the recent introduction of the latest generation of electron counting digital or Direct Detection Device (DDD) cameras into the market, which has been referred to as revolutionary. Electron cryotomography (cryo-ET), on the other hand, is used to visualize the 3D structures of cells in their natural states. When coupled with the newly introduced optical device called phase plate, cryo-ET can resolve the fine details of cellular architectures. In this project, we aim to establish a world-class cryo-EM/cryo-ET shared facility for Life Sciences research in Hong Kong in a timely fashion. Working together HK scientists and international collaborators, we will establish a 200 kV cryo-EM/cryo-ET TEM (transmission electron microscope) system, equipped with a DDD camera for cryo-EM, and a Phase Plate for cryo-ET. We will promote this new system to the research community in Hong Kong for high-impact collaborative research in Life Sciences. Our ultimate goal is to promote research excellence and training young scientists in Hong Kong and beyond.
A Deep Reactive Ion Etching System for Nanosystem Fabrication
Project Coordinator: Professor POON Andrew W O (HKUST)
The objective of this project is to acquire and install a state-of-the-art deep reaction ion etching (DRIE) system for nanosystem research & development in Hong Kong. The proposed equipment demonstrates a 4x higher throughput and a 10x smaller feature size compared with the existing DRIE system. It will enhance research collaborations and shared use of the DRIE system among UGC-/non-UGC-funded institutions and local industry. It will also enhance the nanofabrication technology infrastructure in Hong Kong.
A Platform for Measuring the Physical Properties of Quantum Materials
Project Coordinator: Professor WANG Jiannong (HKUST)
Quantum materials such as the topological state of matters, two-dimensional transition metal dichalcogenides, low-dimensional semiconductors and magnetic semiconductors, superconductors, graphene, and carbon nanotubes have attracted attention from researchers worldwide and represent a very hot research field for their potential applications in next-generation electronics and optoelectronics, and quantum computing and information technology. These quantum materials exhibit many novel properties which can only be investigated under extreme conditions of high magnetic fields and low temperatures. It has been demonstrated in the past that under temperatures below 1K and magnetic fields as high as 16 T many intriguing quantum physical phenomena of materials are revealed, underlying physical principles discovered, and potential applications explored.
In this collaborating equipment application we are requesting a measurement platform for quantum physical properties allowing extreme conditions including high magnetic fields (up to 16 T) and ultralow temperature (down to 0.05 K) with versatile measurement capabilities including DC/AC electrical transport, heat capacity and conduction, scanning probe microscopy, and confocal optical microscopy. The acquisition of this platform will greatly enhance the capability and strength of quantum physics research and material design in Hong Kong, which in turn will strengthen the current collaborations and foster new collaborations across institutional boundaries. The aim of this CRF project is to utilize the proposed platform to enhance our research in the fundamental physics, discovering novel properties of quantum materials through the implementation of a range of collaborative basic research activities.
The success of this proposed study will not only enhance our fundamental understanding of individual material systems, allow us to identify and discover new basic physical principles, but will also ensure to establish a collaborating community in quantum material research in Hong Kong. This will provide a much-needed basis for exploring applications of these quantum material systems in areas such as electronics, optoelectronics, magnetic sensing, energy, and quantum computing and information technology.
Establishment of Third Generation Sequencing Core Facility
Project Coordinator: Professor SHAM P.C. (HKU)
DNA is the genetic material of living things. It is made up of 4 different "bases", commonly represented by the letters A, C, G and T, connected together. The order of these "letters", namely the DNA sequence, determines the species and biological attributes of each living organism. Many diseases are caused by a change in DNA sequences, resulting in birth defect and cancer. Technology for determining the sequence of DNA was invented decades ago and keep improving in sequence length and throughput. Such work requires sophisticated instruments and trained expertise that are not commonly affordable by a single research group. Our Centre, the Centre for Genomic Sciences, was setup to facilitate the sharing of these expensive resources locally in Hong Kong since over 10 years ago. Currently we house multiple DNA sequencers suited for different purposes. Here we propose to acquire the latest generation of DNA sequencer (PacBio Sequel System) which enables a sequence read length of up to 60,000 bases, much longer than is possible with existing technology. The new technology will open up many new opportunities for studying the genome of various potentially pathogenic microbial species, and contribute to the understanding of long-range structural re-arrangement of DNA in diseases. Indeed fruitful findings based on this new technology have been recently published by overseas researchers, and it is important to make this technology readily assessable to local Hong Kong researchers.
Group Research Proposals
Security and Privacy-enhancing Technologies for Cloud Storage of Big Data
Project Coordinator: Professor JIA Xiaohua (CityU)
Over the past decade, more and more organizations and institutions have started adopting public cloud for their storage and big data analytics infrastructure. Along with the trend, advanced and privacy-sensitive applications are posing new challenges that traditional data security and privacy technologies are no longer sufficient to cope with.
In this project, we focus on developing new security and privacy-enhancing technologies for cloud storage that specifically address the challenges brought up by big data, characterized by high volume, high variety and high velocity. Our research findings will enable users to conveniently search the encrypted data, easily verify results from data analytics, and reliably use mobile devices to access cloud services without worrying about security breach. We believe this research will give users faith and confidence towards the use of cloud storage systems, without which the true power of cloud storage cannot be fully unleashed.
A multi-disciplinary study on the beneficial effects of PPARD in physical exercise against diabetic vascular complications: cellular crosstalk and energy metabolism
Project Coordinator: Professor HUANG Yu (CUHK)
Obesity, diabetes and associated cardiovascular complications are one of the top causes of hospitalization of Hong Kong’s aging population. Lack of physical exercise in Hong Kong’s general population is associated with increasing health problems. Regular physical exercise has long been recognized to promote cardiovascular and metabolic health. We know that treadmill exercise improves vascular function in diabetic and obese mice, which involves synchronized activation of molecules including PPARδ and AMPK. Adipose tissue is highly vascularized. However, exercise-induced adaptation of fat is less explored. In addition, the regulation of vascular-adipose loop by PPARδ in the context of type 2 diabetes and obesity is not fully understood.
Using a multi-disciplinary approach, we will investigate whether PPARδ acts as a central regulator of vascular and metabolic benefit of exercise by improving oxidative metabolism in diabetic and atherosclerotic mice; discover the novel molecular targets in endothelial cells induced by PPARδ and enhanced blood flow mimicking the exercise effect on endothelium; elucidate the role PPARδ and AMPK on the regulation of branched chain amino acid metabolism induced by exercise, whether the vaso-protective effect of exercise is mediated through proteins involved in these metabolic pathways to attenuate mitochondrial dysfunction in vascular and adipose tissue.
We hope to address the cardiovascular and metabolic benefit of physical activity through crosstalk among different organs. These findings will provide new knowledge into vascular and metabolic health benefit of exercise; identify new therapeutic targets that mimic exercise-induced benefit; search for new cardiovascular and diabetic risk factors and biomarkers; and help to develop an integrative collaboration platform for studying vascular and metabolic benefits of physical activity and drug therapy.
Elucidating Genomic Signatures Associated with Age-related Decline in Oocyte Quality: From Molecular Mechanisms to Applications
Project Coordinator: Professor LEE Tin-Lap (CUHK)
Female fertility declines dramatically with age, and childbearing at advanced maternal age is a big health concern due to greater risk of early pregnancy-related complications such as miscarriage, aneuploidy, and ectopic pregnancy. The negative impact on fertility caused by advance maternal aging is also implicated in assisted reproduction technologies. A major factor that accounts for fertility deterioration in older women is poor oocyte quality. Recent egg donation and artificial insemination studies have shown oocyte quality is a critical factor for successful implantation and spontaneous abortion. However, the exact molecular mechanisms associated with oocyte aging remains largely elusive to date.
To sparkle new concepts and novel approaches targeting human oocyte aging, our team adopted interdisciplinary approaches and multidisciplinary collaborations with experts from clinical reproductive medicine, genomics, and computational biology to revolutionize our understanding on maternal age effect on human oocyte quality. We have recently reported dynamic genetic and epigenetic changes in mouse oocyte aging model. To elucidate the precise regulations in human model, we will recruit human oocyte samples and apply singlecell genomics technique to capture transcriptomes and methylomes, and apply our recent established bioinformatics pipelines to decode the relationship between aging and oocyte quality. High-throughput RNAi screening will be developed to validate the targets and pathways, and serve as a screening platform for discovering agents with age-reversing activity. The success of this project on human oocytes will contribute to novel knowledges essential to development of new reproductive technologies in Hong Kong and the world.
Development of novel inhibitors targeting the resistance mechanisms of clinical superbugs
Project Coordinator: Dr CHEN Sheng (PolyU)
Carbapenem-resistant Enterobacteriaceae (CRE) is a major class of multidrug resistant bacterial pathogens which often cause untreatable infections among hospitalized patients, posing a worldwide public health threat. Currently, the antibiotic colistin may be used to treat critically ill patients infected by CRE. However, a gene responsible for causing colistin resistance, namely mcr-1, has recently been discovered, threatening to severely undermine the effectiveness of this last resort antimicrobial agent. To urgently address this issue, we believe that it is more realistic to devise effective approaches to preserve the clinical values of both carbapenems and colistin, than to search for new antimicrobial compounds. This optimism is based on our preliminary findings that the key mechanisms of resistance to the carbapenems and colistin are mainly confined to production of three major enzymes/proteins, namely NDM-1(New Delhi Metallo-β-lactamase), KPC-2 (Klebsiella pneumoniae carbapenemase) and MCR-1, implying that inhibiting these proteins alone can effectively restore the activities of both carbapenems and colistin against the majority of the CRE and colistin resistant strains. Our preliminary studies have provided valuable information regarding the structure and functions of these proteins, and helped identify compounds which exhibit promising inhibitory effects against these target proteins. In this work, we strive to optimize the structures of these compounds, with an aim of effectively restoring the antimicrobial activities of both carbapenems or colistin in clinical settings. We first investigate the mode of action of ebselen (Eb) and AMA (aspergillomarasmine A), which are currently the most effective inhibitors of NDM-1, and introduce a novel chemical-linkage approach to enhance their target specificity. Second, we shall adopt a ‘double warhead’ approach by linking NDM-1 and KCP inhibitors (the boronic acid-based inhibitor RPX7009) together through creating a specially designed cleavable linker that may help widen the target spectrum and enhance the bacterial specificity of the inhibitors. Third, we shall develop inhibitors of MCR-1through structural and chemical synthesis approaches. Fourth, we should develop compounds that synergistically increase the antibacterial activity of colistin on mcr-1-bearing bacteria, and investigate their mechanisms of action. Lastly, we will evaluate the clinical application values of the shortlisted compounds, and maintain a library of structurally diverse yet functionally active materials for further modification studies in case resistance arises. We are confident that this research plan will bring about significant breakthrough in the field and discovery of novel drug candidates which can effectively eradicate a broad range of multidrug resistant organisms.
Community and Population Aging in Hong Kong: An Extension of the Hong Kong Panel Study of Social Dynamics (HKPSSD)
Project Coordinator: Professor WU Xiaogang (HKUST)
Like many other developed societies, Hong Kong is facing the great challenge of population aging in the coming decades, with the proportion of elderly people expected to reach 30% by 2034. Understanding how the process of population aging unfolds in different cultures, societies and political environments over time is a central task for social researchers. While many countries have launched longitudinal surveys in the past decade to systematically collect data on health, aging and retirement, Hong Kong still lacks comparable data, let alone evidence-based policy to tackle the challenges of an aging population.
Building on the three waves of the Hong Kong Panel Study of Social Dynamics (HKPSSD) (2011, 2013, and 2015), this project will continue and expand the data collection and analyze the existing data from the special module pertaining the elderly in the HKPSSD to examine the economic, social and health situations facing the elderly population in Hong Kong. Specifically, the main tasks of the collaborative research include: (1) collection of two additional waves of the HKPSSD subsample aged 50 or above in 2017 and 2019, focusing on their income security and personal wealth, family strategies and living arrangement, life trajectory and social participation, and health; (2) analysis of the interplay between economic, health, and social factors in shaping old people’s living conditions and other facets of wellbeing; (3) investigation of the role played by the neighborhood community in providing elderly care and promoting active aging; (4) examination of the family support, intergenerational relationship, and social participation of the Hong Kong elderly, and their interaction with community factors; and finally (5) a comparative study between Hong Kong and Shanghai, two Chinese cities featuring different welfare regimes, to shed light on the institutional factors conducive to effective aging policy.
Panel data collected in this project will supplement the previous waves of the HKPSSD and become a major public good for social science research in Hong Kong and for a comparative study of effective public policy in the context of population aging.
Study of Cooling Effect by Surface Treatment and its Application to Smart Green Buildings
Project Coordinator: Professor CHAO Christopher Yu Hang (HKUST)
More than 30% of electricity consumption in the residential and commercial sectors is for space conditioning in many countries and areas, including Hong Kong. Reducing the energy consumed in space conditioning is an essential requirement for a smart green building. In this study, a smart green wall panel (SGWP) for use in buildings is proposed, providing a solution for building thermal management – an Indoor Thermal Environment Control (ITEC) System. The ITEC system controls the solar heat gain to the buildings, thus reducing indoor air temperature, HVAC energy consumption and the electricity demand. The ITEC system is built using SGWP, a panel that combines two different technologies: a plasmonic structured passive radiative cooler (Task 1) and a hydrophobic-based vanadium oxide (VO2) thermochromic smart window (Task 2).
To realize net radiative cooling below ambient air temperature, a strong reflection of sunlight and a strong emission of thermal radiation with a wavelength within the atmospheric window (8–13μm) must be achieved simultaneously, which is extremely difficult to realize using conventional optical coatings. The proposed study will therefore seek to develop a passive radiative cooler based on plasmonics technology. By changing the plasmonic pattern, the optical properties of photonic devices can be tailored for different spectral regimes, providing great potential to enhance radiative cooling.
However, even with passive radiative coolers on SGWPs to cool the indoor air, substantial energy is still received or lost through the windows. To deal with this, a thermochromic smart window will be developed which automatically changes the intensity of the light passing through it to reduce the energy needed for heating, cooling and lighting. A nano-structured, self-cleaning and hydrophobic material will be coated on top of the smart windows to enhance its visible transmittance. Such coatings have been explored for photovoltaic cells, but never for smart windows.
Lastly, Task 3 aims to evaluate the effectiveness of the ITEC system on thermal management in a combined system setting. The impact of the ITEC system on indoor thermal comfort will also be studied by monitoring a suite of thermal comfort parameters, such as indoor air temperature, relative humidity, mean radiant temperature, air velocity, air flow distribution and location of ventilation units.
Overall, this proposed study will motivate greater research interest in passive cooling, enhance our knowledge of the cooling obtainable through surface treatment and will provide practical design criteria for smart green buildings.
Study of Topological Phases in Condensed Matter and Cold Atom Systems
Project Coordinator: Professor LAW Kam Tuen (HKUST)
Ordinary band insulators cannot conduct electricity due to the presence of a band gap and it takes energy larger than the band gap to excite electrons in the material. Recently, new types of band insulators, called topological insulators, have been discovered. Topological insulators have a band gap in the bulk, similar to ordinary band insulators, such that exciting electrons in the bulk costs finite energy. However, topological insulators support conducting surface states and electric currents can be driven by an arbitrary small electric field.
Recently, it was realized that some superconductors, called topological superconductors, possess bulk single-particle excitation band gap and support gapless excitation modes on their surfaces. The zero energy surface modes of these topological superconductors are called Majorana fermions. A Majorana fermion is an exotic particle, which may have applications in quantum computation. The study of both topological insulators and superconductors is now one of the central topics in condensed matter physics.
In the past few years, more topological phases, such as quantum anomalous Hall insulators and topological crystalline insulators, and nodal topological phases such as Weyl semimetals have been discovered theoretically and experimentally in condensed matter systems.
Remarkably, as studies of topological matter flourish, independent developments in the study of cold atoms, creating synthetic gauge fields and spin-orbit coupling between atoms, have brought these two exciting developments together. The reason is that spin-orbit coupling is the basis for the construction of many types of topological matter, and the great flexibility of cold atom experiments raises the possibility of creating many topological states that are hard to achieve in condensed matter systems, as well as realizing new fundamentally interesting topological states unique to cold atoms.
Our project combines the existing strength of researchers in the areas of topological order of condensed matter systems (KT Law, TK Ng and SQ Shen) and of cold atoms (SZ Zhang and Q Zhou), building a strong theoretical research team based in Hong Kong to explore this new and exciting area of research. The team is expected to produce results at the forefront of this new area of research, with a long-term impacts on the international community. We will also cultivate a new generation of theoretical physicists in Hong Kong who can explore frontier topics in both condensed matter physics and in cold atomic systems.
Making Modernity in East Asia: Technologies of Everyday Life, 19th-21st Centuries
Project Coordinator: Professor K.C.A. LEUNG (HKU)
The main objective of this collaborative project is to establish a new, interdisciplinary way of understanding East Asian modernity through the lens of everyday technology. We ask: Why do East Asian societies engage with modern technology the way they do today? The project is about a history of East Asia that emphasizes the region’s technological dynamism in the last 200 years. It is a history of planning, engagement, maintenance, resilience and innovation. This project will place technology at the center of 21st-century debates on the rise of a new East Asian world order.
East Asia here is defined as a historically connected cultural region shaped both by Chinese cultural influence and western and Japanese colonialism in its more recent history. East Asia is also a field of interactions transcending simple political boundaries.
The project’s basic assumption is “socio-technical systems”, meaning that technologies are not external to a society or culture but are the concrete embodiment of that society’s values and experiences. Our focus on everyday technologies – the ordinary, unglamorous and widespread technologies used in our everyday life – shifts the emphasis from old, exhausted questions on “who invented what first”, or “technological failure, imitation or catching up”, to how technology was and is put to use in East Asia.
The overarching notion of infrastructure as physical, organizational or regulatory networks finally allows us to understand how technological processes have been creating large and small networks transcending national boundaries in the building of modern East Asia since the 19th century.
The research team’s ambition is to build a sustainable platform to synergize research on this topic that has never been treated systematically, and to create in four years an Area of Excellence which will make Hong Kong the world research center for the study of technology and East Asian society.
Mechanisms of renal inflammation: role of Toll-like receptor 4
Project Coordinator: Professor S.C.W. TANG (HKU)
Chronic kidney disease (CKD) is a public health problem worldwide with an ever rising number of kidney failure patients with who require dialysis and kidney transplantation. Recent studies suggest that unsolved kidney inflammation is an important mechanism driving the progression of CKD and in this regard, toll-like receptor 4 (TLR4) plays an important role during this process. However, direct inhibition on TLR4 signaling may impair innate immunity as it is a fundamental defense system of the body against pathogens such as bacteria and viruses. The aims of this project are to define the role of cell-type specific TLR4 signaling in renal inflammation, to identify TLR4-dependent long non-coding RNAs (lncRNAs) and their regulatory mechanisms, and to investigate the therapeutic potential of these TLR4-dependent lncRNAs in renal inflammation. The outcome from this study will improve our understanding on the regulatory mechanisms of TLR4-mediated renal inflammation and will help to develop novel and specific strategies to prevent the progression of CKD.
Environmental studies of the spread of respiratory viruses in a large dense urban social network
Project Coordinator: Professor Y. LI (HKU)
Epidemics of emerging respiratory infections can have a major health and economic impact, and effective control strategies are needed to protect human health. Environmental objects and media provide vectors for the transmission of pathogens between people, including contaminated air (airborne route), contaminated surfaces or objects (fomite route) and large droplets (close contact). Exact route(s) of transmission is unknown for many diseases, and multiple routes are expected to be important for some diseases. The mechanistic process in the routes for viruses to travel from mucus to mucus, that is, from an infected person to a susceptible person, vary for different routes and are yet to be fully revealed. This leads to uncertainty in optimal public health interventions and policies. With its large and dense social network, Hong Kong offers an ideal opportunity for multidisciplinary environmental studies of infection.
In such a city, people are connected by the indoor air they share, by the surfaces they touch, and by the people they meet. In our proposed study, virus spread is considered on two levels: the local room or building level and the city level. At both levels, most studies have focused on the close contact network without considering the mobility of the infected individuals in an urban setting. For a multiple-route disease, the three networks – close contact, indoor contact and surface contact – are coupled, but have usually been studied separately. The mechanisms of the fomite route have been relatively poorly studied.
With a multidisciplinary team, we will carry out the first comprehensive survey of surface touch behaviour, explore how bio-aerosols are deposited or distributed on surfaces, investigate the manner in which viruses transfer and survive, and understand new transfer-resistant mechanisms. New knowledge gained and that from other studies will be integrated into a state-of-the-art triple-network and quadruple-route model. Our new process-based mechanistic model estimates the concentration (number) of viable pathogens or their surrogates at the sources, in the air and on surfaces. We consider a large city of more than 7 million people, 3 million indoor locations and 30 to 50 million high-touch surfaces. We will explore the contribution of the individual routes at both room and city levels, and determine how these are affected by major environmental parameters and environmental control measures. Our developed model will also be used for the analysis of outbreaks and environmental design, and the evaluation of effectiveness of infection control measures.
Regulation and pathogenic role of latent infection of Epstein-Barr virus in nasopharyngeal carcinoma
Project Coordinator: Professor G.S.W. TSAO (HKU)
Nasopharyngeal carcinoma (NPC) is common among Cantonese speaking population living in Hong Kong and southern China. It is closely associated with EBV infection. While EBV readily transforms primary human B cells into proliferative lymphoblastoid cell lines, EBV infection of primary epithelial cells induces growth arrest. EBV establishes life-long latent infection in memory B cells. EBV infection in pharyngeal epithelial cells is predominantly lytic in nature where EBV replicates their episomes to generate infectious viral particles for transmission. Latent EBV infection in healthy oropharyngeal as well as nasopharyngeal epithelial cells is uncommon and rarely detected. Interestingly, EBV infection in nasopharyngeal carcinoma (NPC) is predominantly latent in nature. The switching of lytic infection to latent infection of EBV in premalignant nasopharyngeal epithelial cells may represent an essential step in the pathogenesis of NPC. The underlying mechanisms involved are poorly understood. EBV viral genes notably LMP1 and BART-microRNA may be involved in the transformation of EBV-infected premalignant nasopharyngeal epithelial cells into cancer cells. Prof KW Lo has recently determined genomic alterations of NPC using next generation sequencing and identified frequent genetic alterations of multiple negative regulation of NF-kB, notably TRAF3 and CYLD in NPC (>40%). Furthermore, a mutually exclusive relationship between mutation of negative regulators of NF-kB and expression of EBV-encoded LMP1, a potent activator of NF-kB, was observed in NPC which support an important role of NF-kB activation in the pathogenesis of NPC. Interestingly, aberrant NF-kB activation, with activation of complex of p50/p50 dimers and bcl3, is the common form of NF-kB activation in NPC. We postulated that aberrant NF-kB signaling may support establishment of latent EBV infection and contributes to the pathogenesis of NPC. We will generate TRAF3 and/or CYLD knockout immortalized nasopharyngeal epithelial cells for EBV infection. Furthermore, we will clone EBV directly from our recently established EBV+ve NPC cell lines examine to study their infection and transformation properties. We have also established advanced genomic editing techniques to clone and edit the EBV genome from NPC. The contribution of aberrant NF-kB activation to latent infection in premalignant nasopharyngeal cells, regulation of EBV gene expression and host innate immune response to EBV infection will be examined systematically. Elucidation of events underlying establishment of latent EBV infection in premalignant nasopharyngeal epithelial cells will contribute to the understanding of NPC pathogenesis.
Advancing China's Urbanization inside out: Urban Redevelopments in Chinese cities amidst accelerated urban transition
Project Coordinator: Professor G.C.S. LIN (HKU)
In recent years China’s urbanization has shifted its emphasis from urban sprawls into urban renewals. This proposed project mobilizes a team of experienced researchers with different and yet complementary expertise to work at the interface of three lines of scholarly enquiry concerning China’s urban redevelopment—a mission that would not be possibly accomplished by working on the individual components in isolation of each other. Our objectives are to identify the pattern and process of urban redevelopment, analyze its social, political, and institutional underpinnings, and evaluate its effects upon land use efficiency, social equity, and spatial inequality. Through a coordinated collaboration in quantitative analyses of statistical data, multi-local questionnaire surveys, and personal interviews to be carried out in Beijing, Wuhan, and Guangzhou, this proposed collaborative project provides a valuable opportunity for effective synergism among the participating investigators and institutions concerning urban China research. This research will fill noticeable gaps in urban China studies, contribute significant insights into the dynamism of state power and spatial transformation, and shed new light over the functioning of property rights during market transition. Its findings will be valuable to government agencies, land use planners, business communities, teachers and students in Hong Kong and China’s mainland, with the potentials to grow into an AoE on urban China in which Hong Kong has accumulated world-class institutional capacity and well-recognized intellectual strength.
Multi-scale single-cell optical imaging: architecture and biomedical applications
Project Coordinator: Dr. K.K.M. TSIA (HKU)
In biology and study of diseases, identifying the diversity and origins of different cell types and their functions in tissues down to single-cell precision is an essential yet daunting task. Continuing advancement of the current technologies for single-cell analysis is fundamentally compounded by two challenges. First, they run short of throughput for measuring sufficiently large sample sizes of thousands to millions of cells. It is a critical attribute when it comes to detecting unknown and rare populations of cells (e.g. rare cancer cells, stem/progenitor cells) that hold the key to understanding health, repair and disease. Second, current single-cell measurements predominantly rely on the repertoire of biochemical markers which helps reveal the molecular signatures (e.g. gene expression), they however become ineffective when there is little prior knowledge about the biochemical markers, not to mention their extremely costly and slow process.
As a multidisciplinary team of researchers from biomedical science, photonics engineering, computational imaging, and computer systems, we aim to take an integrative approach in this project to address the aforementioned grand challenges. Specifically, the project focuses on development of an optofluidic single-cell imaging platform integrated with a high-performance and versatile computing platform. It is capable of capturing an unprecedented set of biophysical and biochemical biomarker data for single cells at high-speed, high-spatial-resolution, and high-sensitivity. Processing massive amount of data at high speed, the proposed technology allows accelerated deep image analytics for automated, multi-scale classification of thousands to millions individual cells. The established system will be applied to perform a deep characterization of the transition states in the process of stem cell differentiation. Success will help empower the new paradigm of single-cell analysis, in turn enabling new and fundamental questions in biology and disease to be addressed.
Optogenetic Functional MRI Dissection of Long-Range Brain Networks
Project Coordinator: Professor E.X. WU (HKU)
One grand challenge for the 21st century is to achieve an integrated understanding of the brain circuits, particularly the spatiotemporal patterns of neural activities that give rise to functions and behavior. In this group research project, we will develop an innovative neuroimaging approach - the combined use of optogenetic neuromodulation with functional MRI (fMRI). With this capability, we will investigation two fundamental questions regarding long-range brain circuits: What dynamic response properties govern the network activity propagations and interactions? What is the functional relevance of the long-range, low-frequency neural interactions? Specifically, we will develop optogenetic fMRI (og-fMRI) technology to capture and analyze whole brain activities with much improved sensitivity, specificity and causality. We will then deploy this imaging capability to systematically interrogate the spatiotemporal response properties of two distinct long-range networks, namely, thalamo-cortical and hippocampal-cortical networks, by optogenetically activating and deactivating the excitatory neurons in several thalamic and hippocampal structures, respectively, together with electrophysiological recording approaches. Finally, we will systematically examine the functional effects of low-frequency optogenetic stimulation within these two networks on brain responses to external sensory stimuli. The outcomes from this group project will enable us to provide mechanistic insights into the spatiotemporal recruitment of spatially segregated but functionally integrated neuron populations, and elucidate the functional relevance of low-frequency activities within the long-range networks.