Theme-based Research Scheme 2021/22 (Eleventh Round) Layman Summaries of Projects Funded

Theme 1: Promoting Good Health
Project Title: Virological, Immunological and Epidemiological Characterization of COVID-19
Project Coordinator: Professor Leo Poon (HKU)

The causative virus of COVID-19, SARS-CoV-2, is likely to become an endemic infection in humans. Mutations in the SARS-CoV-2 genome will continue to arise in the future. This multidisciplinary team will address two key COVID-19 research areas: 1) monitoring genotypic and phenotypic changes in SARS-CoV-2 and 2) investigating immune responses following natural infection or vaccination. Our project will help to reveal COVID-19 transmission and pathogenicity and identify vaccination strategies against SARS-CoV-2. Information generated from this work will be shared with relevant stakeholders in real time to inform healthcare policy.

The proposed studies will leverage our well-established research program on COVID-19. The first specific aim of our study is to experimentally identify SARS-CoV-2 strains that are of public health concern (e.g., Variants of Concern). We will focus on genetic and phenotypic characterization of naturally occurring viruses using a range of in vitro and in vivo experimental models. Mutations that lead to phenotypic changes will be further confirmed by reverse genetic approaches. We will also use next generation sequencing technology to understand the virus population dynamics in a transmission chain. The second specific aim is to study COVID-19 immune responses. We will study immune responses induced by natural infection or vaccination in community cohorts and in patient cohorts. Adults and children with virologically confirmed SARS-CoV-2 infection will be followed up over 3 years for a detailed characterization of their antibody and T cell responses. These individuals will be monitored for re-infection. The quality and kinetics of immune responses triggered by COVID-19 infection or commercial COVID-19 vaccines will be assessed and compared. We will also use animal experimental models to develop and optimize vaccination strategies for enhancing the protection provided by COVID-19 vaccines against disease and transmission. Relevant viruses obtained from the first specific aim, particularly potential immune escape variants, will be used to investigate effects of viral mutations on COVID-19 immune responses. We will use bioinformatics approaches to identify potential cellular and/or serological markers that can be used as correlates for protection and viral epitopes of vaccine potential. We will use these results, together with epidemiological data, to understand COVID-19 transmission in Hong Kong and beyond.

Theme 1: Promoting Good Health
Project Title: Ecology, Molecular Virology and Pathogenesis of SARS-CoV-2: From Bedside to Bench and Back
Project Coordinator: Prof Dong-Yan Jin (HKU)

With our study and discoveries of coronaviruses (CoVs) in the past 18 years, multidisciplinary research in this project will be carried out in three intertwined areas to address key scientific questions surrounding ecology, molecular virology and pathogenesis of SARS-CoV-2, thereby paving the avenue to conceptually new approaches for early diagnosis, prevention and treatment of COVID-19, essential to bringing an end to the pandemic. First, we will derive new insights into the origin and evolution of SARS-CoV-2 by analyzing one of the world’s largest collection of samples from bats and other animals. Concurrently, we will continue to discover emerging variants of SARS-CoV-2 with altered pathogenicity and transmissibility. We will also define the mechanism of asymptomatic SARS-CoV-2 infection in bats and humans. This will provide the materials and basis for the next part of our project. Second, we will unravel new mechanism of SARS-CoV-2 entry and replication. We will also characterize the roles of several lineage-specific accessory proteins in SARS-CoV-2 biology and pathogenesis. Forward genetic screens based on RNAi and CRISPR technology will be performed to identify novel host dependency and restriction factors. Finally, we will pursue translational research to revolutionize diagnosis, vaccine development and treatment of COVID-19. Concepts established in our project will be harnessed to design and develop new strategies, methods and leads for early and rapid diagnosis, immunization with live attenuated and synthetic vaccines, as well as therapeutic treatment targeting either the virus or the host.

Theme 1: Promoting Good Health
Project Title: Translating Disease-Mechanism Discoveries to Improve Treatment of Biliary Atresia, an Intractable Newborn Liver Disease
Project Coordinator: Prof Vincent Chi Hang Lui (HKU)

Biliary Atresia (BA) is a devastating inflammatory disease of the bile ducts affecting 5-20:100 000 newborns, with the highest frequency in Asians. BA diagnosis is challenging, sometimes missed or made late. Untreated, infants die from liver fibrosis and failure. Kasai surgery is the first line treatment but bile drainage is only achieved in 50% of patients. Moreover, Kasai surgery only replaces the extra-hepatic bile duct, and the intra-hepatic cholangiopathy is un-remedied. Hence patients often develop biliary infection and sclerosis, leading to liver failure requiring liver transplantation which presents challenges from organ shortage and long-term immunosuppression. BA thus represents a huge medico-societal problem, improved diagnosis and new therapies are therefore urgently warranted. The root cause for lack of progress in BA treatment lies in the poor knowledge of its underlying pathogenetic mechanisms. We are a new BA consortium, which comprises a team of clinicians and scientists, strengthened by the addition of international experts with unique complementary expertise, who are poised to pioneer BA research, diagnosis and therapy. Building on our promising discoveries recently published in J Hepatol, we propose to advance BA research to improve our understanding of its disease mechanisms using novel, beyond state-of-the-art organoid-based systems, dissect disease heterogeneity through genomics and transcriptomics, and pursue novel therapeutic leads with pre-clinical testing.

These goals will be achieved by a multi-pronged approach. We will 1) use cholangiocyte organoids from human livers/induced Pluripotent Stem Cells, multi-cell type organoids, and cells/organoids seeded onto liver extracellular matrix-derived gel to assess the pathobiological roles of various cell types, paracrine/guidance/matrix cues, toxins, virus, immune-inflammatory dysfunction and fibrosis; 2) integrate whole-exome (n=400 BA trios) and tissue transcriptomic (n=50) analyses with comprehensive clinical/phenotype information to stratify BA patients and discover novel disease mechanisms; 3) pursue targeted therapies, using BA organoids as clinical surrogates to test drug repurposing on amyloid-beta deposition, ciliary dysfunction (our new findings); immune-inflammation and fibrosis. The findings will inform clinicians on patient stratification and provide evidence for implementing clinical trials of novel therapies towards regeneration of a functional biliary tree. In sum, by combining leading clinical expertise and cutting-edge technologies, we will break new grounds in the understanding of a devastating liver disease and enhance its diagnostics and therapy development. Advances in this project also serve as a model for discovery research of other gastrointestinal diseases.

Theme 1: Promoting Good Health
Project Title: Stem Cell-niche Interactions in Tissue Maintenance and Engineering
Project Coordinator: Prof Ting Xie (HKUST)

Stem cells support normal development and maintain tissue homeostasis in adults through their unique ability to replicate and differentiate into specialized cells. They have been proposed as treatments for degenerative diseases such as Parkinson’s disease, Alzheimer’s disease and type I diabetes. Cancer stem cells can also replicate, driving tumor growth, metastasis and relapse. The age-dependent decline of stem cell activity has been linked to age-related deterioration in tissue functions. To harness the full potential of stem cells as therapeutic agents, ongoing efforts have been made to combine them with biomaterial scaffolds for the generation of transplantable tissues or organs to treat degenerative diseases. Thus, knowledge of stem cell development and aging is critical for the development of stem cell-based therapies to combat many human diseases. The major obstacle in realizing the full potential of stem cell therapy is the lack of sufficient knowledge of the regulation of stem cell activities inside intact tissues. In this TRS project, we propose to investigate the molecular mechanisms underlying stem cell maintenance, differentiation and aging in model organisms such as Drosophila, zebrafish and mice. A team of investigators from HKUST, HKU and CUHK with complementary expertise, experience of successful collaboration and with outstanding research records has been assembled to reveal how the microenvironment, or niche, controls stem cell behaviors and functions at the molecular and cellular level using a combination of advanced genomic, genetic, molecular, biochemical and developmental approaches.

Theme 2: Developing a Sustainable Environment
Project Title: Healthy and Resilient City with Pervasive LoCHs
Project Coordinator: Prof Jianlei Niu (PolyU)

Heatwaves exacerbated by the Urban Heat Island (UHI) effect can make urban environments unbearable. US epidemiology studies indicated that there was a correlation between high temperature and morbidity and mortality. In Hong Kong, high-temperature events have significant impacts on the mortality risk and hospitalization rate. People in dense urban environments tend to stay indoors longer, become more sedentary and consume more energy to run air-conditioners. Studies in Developmental & Behavioral Pediatrics show that outdoor playtime is associated with children’s body mass index scores and obesity. It is believed that systematically designed ‘open streets’ programs could develop into heat resilience hubs like an oasis in a desert, enabling the urbanites to reclaim the outdoor. The importance of such projects cannot be overstated considering rapid global urbanization while the planet faces irreversible climate change.

This project intends to build upon the team’s successful RGC Collaborative Research Fund project, which demonstrated that outdoor localised comfort hubs (LoCH) exist in a town center even in a high-density urban environment like Hong Kong with a hot, humid summer, and that, in particular, the semi-outdoor space created by lift-up building design was favorable for thermal comfort due to the combined effects of shading and induced wind downwash. We found that, even if we cannot change the climate of a whole city, we can create LoCHs to pervade all neighbourhoods in proportion to their scales to raise thermal comfort. By employing a scientific microclimate design methodology based on advanced modelling and simulation of wind, heat, and moisture at the early building design and planning stage, thermal and wind comfort can be maximized and thermal stress risk can be minimized, via an optimized combination of building forms and their relative locations in a precinct with assisting vegetation, water, surface materials, and ad hoc pavilions and other mechanical means, and the same idea can also be applied to infill redevelopment projects and other property development to create LoCHs in an existing neighbourhood. In this proposed project, “self-driving” optimization of building forms and architectural master-plan via big data analytics and artificial intelligence (AI) programming is the target deliverable, which combines GIS, building information modeling (BIM), enhanced with high-resolution wind and thermal microclimate modelling down to the scale of the pedestrian level. The state-of-the-art of computing power will be put into use in conventional architectural design and planning practice to improve contemporary and future urban liveability and sustainability, and to cope with a rapidly changing climate.

Theme 3: Enhancing Hong Kong's Strategic Position as a Regional and International Business Centre
Project Title: Developing Hong Kong as a Global Green Finance Centre
Project Coordinator: Prof Chu Zhang (HKUST)

Green finance is a worldwide phenomenon and an emerging intellectual discipline. However, intellectual progress in green finance has lagged behind industry development. The challenge lies in the intrinsically interdisciplinary nature of green finance, which requires synergistic collaboration between scholars across disciplines. This project assembles an interdisciplinary team of scholars in finance, environmental science, public policy, technology, as well as former policymakers and experienced practitioners. Our goal is to advance the intellectual frontier of green finance by conducting a series of cohesive studies that address fundamental research questions, including: (1) the impacts of environmental risks on financial markets and financial decisions; (2) climate risk modeling and derivative products; (3) the financing of green infrastructure projects; (4) enabling technologies of green finance; (5) talent capacity building and talent development; and (6) the effectiveness of policy and regulatory instruments in developing green finance in Hong Kong. We will adopt a “Think-and-Do” approach to develop technology prototypes and proof-of-concept financial products in collaboration with industry partners and government units. In other words, unlike the observer’s approach in conventional empirical economics and finance, we will gather insights from academic research to guide execution, participate in actual implementation of green finance tasks, and advance the intellectual frontier of the discipline, benefiting both government and industry stakeholders. This study is the first of its kind in both nature and scale. The associated educational programs and policy recommendations will position Hong Kong to be an international green finance center. The outcomes of this project will also advance the intellectual development of green finance and make long-lasting worldwide impacts.

Theme 4: Advancing Emerging Research and Innovations Important to Hong Kong
Project Title: Multimodal Approaches to Testing and Prediction in Early Academic Achievement: Chinese, English, and Mathematics
Project Coordinator: Prof Catherine McBride (CUHK)

Early prediction of literacy and mathematics variability, including learning difficulties, is a global concern. For example, in Hong Kong, up to 12.6 % of the population suffers from dyslexia; difficulties in English- and mathematics-learning are also widespread. Learning of Chinese, English, and mathematics is influenced by multiple factors, related to the environment, the brain, and genetics. These factors often influence one another in complex ways. Promoting optimal learning and preventing learning failures depend on understanding how these factors work together to affect individual learning. Currently, a comprehensive assessment of learning requires in-person, individual testing. This traditional approach is labor-intensive and costly for both teachers/clinicians and families, leaving many children with assessment needs unable to gain access to valuable testing in a timely manner. Importantly, early identification of risk for learning difficulties is crucial for optimal remediation. The current educational environment in Hong Kong, with COVID an ever-present threat, makes clear the urgency of online, low-cost, efficient, and accessible assessment for early Chinese, English, and mathematics performance. Our study seeks a) to establish multimodal, longitudinal models of Chinese, English, and mathematics learning and b) to design and implement online testing tools for children’s performances in these three fundamental areas. This study builds upon a large, comprehensive data set of Hong Kong Chinese primary school children, including both twins and singletons. The children have been tested face-to-face on various cognitive-linguistic and academic skills; we also have information on brain/neural processing, genetics, and family background for many. In this new study, we will expand this data set to include more families. We will also design and develop online versions of various predictive assessments of Chinese, English, and mathematics and implement automatic scoring features for these online tasks, improving the efficiency of these tools in order to enable access to immediate test results. All data (including genetics, home and school background, demographics, neuro and behavioral skills) will be aggregated so as to test multimodal predictors of children’s Chinese, English, and mathematics performances. This data set will be among the most comprehensive on children’s early learning worldwide. Our data analyses can help to identify children at risk for learning difficulties at the earliest age possible, when remediation is most effective. Moreover, with our easy-to-implement tools and rich dataset, we can optimize learning profiles for each child. Such a profile is essential for the design of instructional and learning programs tailored to help each child to learn most effectively. We aim to improve the education quality in Hong Kong by providing inexpensive and efficient online assessment tools of academic and cognitive skills to better support children, parents, teachers, and clinicians.

Theme 4: Advancing Emerging Research and Innovations Important to Hong Kong
Project Title: Building Platform Technologies for Symbiotic Creativity in Hong Kong
Project Coordinator: Prof Yike Guo (HKBU)

Against the backdrop of a fast-advancing technological world, the convergence of arts and technology has ushered into a new era of art technology (Art Tech), disrupting how humans create, receive, and respond to arts and culture.

This research project stands at the forefront of the arts and science nexus, harnessing the power of science and technology to radically advance human and AI interaction. It aims to contribute to the long-term sustainability and viability of the arts ecosystem in Hong Kong, exploring new opportunities that AI-based Art Tech could bring to our city.

This will enable new modalities of artistic creation and consumption triggering important socio-economic impacts, thus stirring up a powerful rippling resonance in areas such as business, healthcare and education. By combining the expertise and experience of members from different fields including AI, cognitive science and arts, the project’s team have set three main goals to achieve:

Task 1: AI Technology for Artefact Creation: the development of new algorithmic systems for artefact creation, driven by cognitive and physiological data together with human experience and behaviour.
Task 2: Art Tech for Manifestation and Delivery: the creation of new modes of artistic content and delivery mechanisms via an immersive and interactive XR media platform for audience engagement and arts education.
Task 3: Platform Deployment and Applications: the investigation of the potential of arts and technology convergence for augmenting human creativity. The outcomes of this project are expected to include:
Task 3.1. Application Projects – dedicated artistic deployments for testing new technologies while reaching global dissemination.
Task 3.2. Research Theatre – a novel platform for ground-breaking innovations in the realms of Art Tech.
Task 3.3. Digital Art and Policy Network – the region’s most comprehensive digital art network, linking Hong Kong to a wider global Art Tech development network. Leveraging the recent development in AI technologies, Art Tech will radically change the art world and creative industries, creating significant social, educational, and economic benefits in Hong Kong and the Greater Bay Area. This research project is well poised to offer a powerful interdisciplinary framework to address pressing societal challenges we face in a post-COVID pandemic era, and brings new opportunities for broad and meaningful socio-cultural-economic growth in Hong Kong.