Theme-based Research Scheme 2024/25 (Fourteenth Round) Layman Summaries of Projects Funded

Theme 1: Understanding Diseases and Disease Prevention
Project Title: Sustained cART-free HIV-1 Control by Immunotherapeutic Interventions
Project Coordinator: Prof Zhiwei Chen (HKU)

Abstract

The HIV/AIDS pandemic has resulted in 39 million people living with HIV-1 (PLWH) and 40.4 million deaths since 1981. In Hong Kong, despite active prevention efforts and the timely introduction of combination antiretroviral therapy (cART), the cumulative number of PLWH has increased to 11 943 in 2023, requiring an estimated annual cART expenditure of HK$750 million. The PLWH community faces challenges Drug resistance, cumulative toxicities, and stigma associated with cART. Ending the HIV/AIDS pandemic still requires scientific breakthroughs in vaccine and cure research. To achieve this goal, our overall objective is to determine effective immunotherapies that can potentiate host immunity to achieve sustained cART-free HIV-1 control, a state of viral suppression below the limit of detection for a prolonged period in PLWH.

With previous support from RGC’s General Research Fund / Collaborative Research Fund / Theme-based Research Scheme, several important findings led to our hypothesis that an effective immunotherapy will provide sustained cART-free HIV-1 control by potentiating host immunity. Importantly, our research outputs include the conduct of a double-blind, placebo-controlled Phase I trial of the human PD1-based vaccine ICVAX among PLWH. Building on these outputs and our team’s expertise, we are applying for this new project to focus on achieving sustained cART-free HIV-1 virologic control in relevant animal models and most importantly among PLWH in clinical trials. Using advanced techniques of systems virology and immunology, we aim to accomplish three specific research themes: (I) To determine the mechanism of PD1-based vaccine-mediated 6-year cART-free virologic control in SHIV-infected rhesus monkeys; (II) To determine the impact of PD1-based vaccine on the viral reservoir among cART-treated PLWH; and (III) To investigate sustained cART-free HIV-1 virologic control using analytical treatment interruption and combination immunotherapy. Our findings will enrich the knowledge on mechanisms of immune protection, which are critical for saving the lives of PLWH, and for reducing the toxicity or the resistance of cART as well as financial burden for the Government and individuals.


Theme 1: Understanding Diseases and Disease Prevention
Project Title: Understanding Phenotypic Plasticity in Hepatocellular Carcinoma to Mitigate Therapy Resistance and Tumor Recurrence
Project Coordinator: Prof Stephanie Kwai-yee Ma (HKU)

Abstract

Hepatocellular Carcinoma (HCC) is one of the most prevalent and aggressive malignancies in this region. The overall prognosis is unsatisfactory due to late presentation, drug resistance, and frequent tumor recurrence. Cancer cell plasticity is now a recognized hallmark of cancer, allowing cancer cells to undergo molecular and phenotypic changes that permit them to adopt different differentiation states. HCC tumors are known to contain more stemness or less differentiated cell states that are resistant to therapy and are associated with the development of tumor relapse. This team has a long-standing interest in the area of liver cancer stem cell biology, has advanced understanding, and contributes unique resources to the field.

Despite substantial progress, important knowledge gaps remain in the process by which this cell state is controlled, and opportunities for therapeutic interventions targeted at stemness are hindered by the availability of appropriate technologies in the past. Recent technological breakthroughs in barcoded CRISPR-Cas9 and combinatorial genetic technological platforms for high-throughput functional screening, computational tools to effectively model cell state dynamics and trajectories, spatial and single-cell multi-omics to better understand heterogeneity and the tumor microenvironment, and chemical biology and approaches for cancer drug discovery have enabled research in new dimensions that have not been previously possible.

The challenge lies in comprehensively defining the functional attributes of the various intrinsic and extrinsic factors, as well as their interplay, which contributes to a more aggressive stemness and drug-resistance state in HCC, and in designing / validating new proof-of-concept therapies targeted at stemness. We hypothesize that variation in the regulation of genes and proteins, as well as immune regulatory cells in the tumor microenvironment, affects the onset, progression, and severity of HCC and that the maintenance of a more stemness state plays a critical role in the process.

As an internationally recognized leading multidisciplinary team of scientists and clinicians with a successful history of collaboration and unique expertise that spans the fields of basic experimental cancer biology, hepatobiliary surgery, immunology, computational biology, bioinformatics, synthetic biology, and chemical biology, we propose to leverage new technological breakthroughs contributed by our team, together with our expertise in liver cancer stem cell biology and our collective exciting preliminary data, to continue our investigation on the comprehensive understanding of HCC stemness through a multi-pronged approach consisting of four distinct but highly interconnected programs. By utilizing barcoded CRISPR-Cas9 and our unique combinatorial genetic technological platforms, (1) we will systematically identify and characterize functional genes and/or their combinations that are critical for HCC stemness. By applying both in-house and publicly available computational methods to our mouse and human HCC datasets, (2) we will identify stem / progenitor features and differentiation states associated with cancer cell plasticity in HCC. Through the use of spatial and single-cell multi-omics on our unique datasets, (3) we will elucidate the microenvironmental landscape of HCC in relation to cancer stemness, phenotypic plasticity, and drug resistance. The first three aims will cooperatively define novel intrinsic and extrinsic regulators and provide mechanistic insights into phenotypic plasticity as a scaffold to guide accelerated progress in uncovering new stemness vulnerabilities, which will feed into the last objective (4), where we will utilize chemical biological approaches to discover and develop novel therapeutic interventions against HCC stemness. Collectively, the project will generate unique information for evidence-based translational applications to improve the diagnosis and treatment outcomes of HCC patients by targeting plasticity and stemness.


Theme 2: Developing a Sustainable Environment
Project Title: A Digital Twin for Enhancing Coastal Resilience against Extreme Storm Surges in Hong Kong
Project Coordinator: Prof Jidong Zhao (HKUST)

Abstract

Hong Kong, like many other coastal cities, faces risks from severe weather events such as typhoons, high waves and storm surges. These weather phenomena can pose great dangers to individuals and harm coastal structures. Notably, recent super typhoons like Hato (2017), Mangkhut (2018), and Saola (2023) have caused significant damage in Hong Kong. The economic losses from Mangkhut (2018) alone exceeded HK$4.60 billion. These events underscore the importance of understanding the impact of climate change on coastal communities to enhance our ability to better predict and manage these risks. With global warming, we anticipate a rise in extreme weather occurrences, particularly extreme storm surges. Coastal cities, including Hong Kong, need to take measures to enhance the resilience of their coastlines and be well prepared to better respond to these challenges.

This project focuses on developing a predictive digital model for Hong Kong's coastlines to enhance preparedness for extreme events, particularly extreme storm surges. This digital model, known as a digital twin of actual coasts, leverages cutting-edge approaches in computational mechanics, data science, machine learning and artificial intelligence (AI), and remote sensing to advance our understanding and our ability to predict coastal land-wave interactions. The primary objective is to provide accurate forecasts to support decision-making on mitigating the impacts of severe weather events, especially extreme storm surges.

The project encompasses four key tasks: (a) creating a digital representation of the coast of Hong Kong; (b) developing detailed models of coast-wave interactions; (c) constructing an AI-based prediction system for the coastal areas; and (d) establishing an early-warning system with the digital twin system at its core for potential hazards. The AI-driven, digital twin coast will utilize real-time monitoring data for practical predictions, with a particular focus on vulnerable zones and low-lying regions.

The models can help predict the occurrence of giant waves along the Hong Kong coastline, accurately and efficiently simulate their complex interactions with coastal topography and structures, and provide scientific forecast and assessment of the potential damage to coastal defense infrastructure from giant waves, as well as the flooding impacts on nearshore areas. Deep learning methods will be employed to generate real-time maps of areas at risk of flooding, inundation and damage. The system will cover the entire Hong Kong coastline, utilizing advanced monitoring technologies to obtain real-time data for forecast and feedback, in order to promptly respond to coastal safety and disaster risks under extreme weather conditions, and enhance the resilience of vulnerable nearshore and low-lying areas. After its completion, this platform system can be promoted to other coastal cities and regions, including the Greater Bay Area.

Theme 2: Developing a Sustainable Environment
Project Title: High-Frequency, High-Power and High-Efficiency Wireless Power Transfer Technologies
Project Coordinator: Prof Ron Shu-Yuen Hui (HKU)

Abstract

The power level of wireless power transfer (WPT) traditionally decreases with increasing operating frequency. Existing wireless power standards typically have operating frequency in the range from 85 kHz to 300kHz and charging power up to 2.2kW for portable equipment and 22kW for electric vehicles. Recently, the WPT industry is considering the use of Mega-Hertz (MHz) operation to improve system performance.

The operating region of high-frequency (HF) and high-power (HP) is a generally uncharted territory of WPT, although some individual research works have been reported. MHz operations pose three technological hurdles including the lack of (i) WPT resonators with precise parameters suitable for mass production, (ii) low-loss gate drive and power inverters with low switching losses and (iii) low-loss electromagnetic shielding materials for MHz operation.

This proposal overcomes these problems with three new and integrated approaches for HF-HP-High Efficiency (HE) WPT applications. We shall study (a) new MHz printed-circuit-board (PCB) resonator structures with high quality factor, (b) new MHz gate drive circuits for soft-switched power inverters, and (c) low-loss metasurface for electromagnetic shielding for HF-HP-HE WPT systems. The PCB resonators are suitable for mass production with precise parameters, the power inverters are suitable for high-power applications, and the metasurface shielding offers new solutions to enclose the magnetic field and therefore avoid human exposure to electromagnetic field.

The expected outcomes include new WPT technologies for the HP range of 100W to 1kW (for demonstration purposes), HF range from 1MHz to 13.56MHz and HE exceeding 95%. The potential applications include wireless charging of consumer electronics, laptops, drones, e-bikes and mobile robots. Preliminary results have indicated the feasibility of this proposal. The Hong Kong Government has clear policy to stay as a technology hub for the Greater Bay Area in China. The project team has previously pioneered planar WPT technology that led to the world’s wireless charging standard “Qi”. The success of this new project will provide new technologies for the uncharted territory of HP, HF and HE WPT regime, strengthening Hong Kong as a globally leading innovation hub in WPT technology.


Theme 3: Enhancing Hong Kong’s Strategic Position as a Regional and International Business Centre
Project Title: Enhancing Hong Kong’s Role in Sustainable Supply Chain Finance via Technology Transformation
Project Coordinator: Prof Jiheng Zhang (HKUST)

Abstract

Hong Kong has been leading regional economic development by playing a pivotal role in global supply chains, which are broadly construed as the supply-demand networks that coordinate physical product flow, financial flow, and information flow. The ever-changing technology, which has advanced at an unprecedented pace, has revolutionized the way we do business in the new knowledge economy and poses both opportunities and challenges. Modern supply chains face three major challenges. First, small and medium enterprises, despite their significant economic role, struggle with limited capital access. Second, environmental pressures, spurred by regulations and societal demands, have thrust carbon costs into the limelight, creating a new dimension of consideration in addition to traditional labour and material costs. Lastly, the digital transformation, though promising, highlights inefficiencies from fragmented data and a lack of cohesive decision-making tools, leaving many decisions anchored in intuition rather than scientific analysis.

To address these challenges, we've gathered a team of seasoned experts from the fields of data analytics, operations research, and finance, aiming to provide tools to enhance Hong Kong's capabilities in orchestrating the supply-demand networks. Under our proposed Data, Modelling, Analysis, Computing framework, we aim to craft an innovative analytical approach, seamlessly fused with cutting-edge financial technology. Our strategy unfolds in four core areas: (1) the design of a blockchain consensus mechanism; (2) integration of supply chain data through decentralized finance; (3) understanding the transformative impact of carbon costs on supply chains; and (4) leveraging data-driven analysis to enhance supply chain efficiency. While Hong Kong lagged in areas like digitization during the last technology wave, the emphasis on sustainability and finance in modern supply chain provides Hong Kong a golden opportunity. Through this project, we aim to not only help Hong Kong catch up but also position it to lead, making the most of our strengths and opportunities in the evolving global environment.


Theme 4: Advancing Emerging Research and Innovations Important to Hong Kong
Project Title: Mechanisms and Key Technologies of Multi-Sensory Emulation Wearable Devices (MSEWD)
Project Coordinator: Prof Xiaoming Tao (PolyU)

Abstract

The true metaverse experience shall be able to replicate the five human sensations (i.e. Touch, Sight, Hearing, Smell and Taste). Despite modern technology having relatively well addressed the simulation of Sight and Hearing senses, there has been a lack of wearable technology based on scientific mechanisms for simulating the Touch and Smell senses. In this project, we attempt to emulate the less developed but urgently needed Touch (tactile) and Smell (olfactory) sensations through the study of multi-sensory emulation wearable devices (MSEWD) that reveal their operational mechanisms, and develops key technologies and applications.

The novelties of the project include: (1) First-of-its-kind emulation mechanisms using fibrous structures and their bionic actuation devices for delivering mixed scents and tactile sensation. (2) Novel olfactory neuron biosensors for mixed scents, edge-computing fibre sensors and sensing methods for tactile and acoustic signals, as well as fabric based wearable acoustic stethoscope equipped with machine learning models. (3) Artificial Intelligence (AI) Models that link the human olfactory and tactile perceptions to the measured signals obtained by biosensors. (4) Algorithms for controlling the bionic emulation devices. (5) More immersive experiences offered by MSEWD via emulated tactile and olfactory sensations.

Our target MSEWDs include a device that senses and simulates olfactory sensation by AI controlled scent making and dispersion of mixed scents; a fabric tactile emulator that senses and tunes reactive forces and temperature by changing its rigidity, dimension, surface morphology and thermoelectric properties; and a wearable fabric-based acoustic stethoscope that continuously detects the location and intensity of sound generated from human internal organs with the aid of machine learning models.

Our team has strong research track records in flexible materials, sensors and actuators for Internet of Things (IoT), wearable systems and biomedical applications, electronic fabrics, mathematics for artificial intelligence, acoustics and signal processing. We also have excellent track records of knowledge transfer with significant impact on society. In the Research Assessment Exercise 2020 conducted by the University Grants Committee, two impact cases contributed by the Project Coordinator and the team members were rated 4* (world-leading) by the Engineering panel and the Physical Sciences panels. Several start-up technology companies have been established from the team.

Significant impacts of this study are envisaged, as it will open a new research topic area with great potential not only to fundamentally alter the course of metaverse and Augmented Reality / Virtual Reality, but also to influence industrial fields as diverse as healthcare, IoT, smart city, art technology, robotics, education, sports, personal protection, fashion, textiles and entertainment, many of which are areas where Hong Kong has inspiration for further developments.


Theme 4: Advancing Emerging Research and Innovations Important to Hong Kong
Project Title: Social Robots with Embedded Large Language Models Releasing Stress among the Hong Kong Population
Project Coordinator: Prof Johan F. Hoorn (PolyU)

Abstract

“Family wellbeing is the foundation of a harmonious society that promotes psychological health and individual flourishing” (Zeng et al., 2023). However, Hong Kong made it to The Lancet as an exemplary case of depression following broad social unrest. Around 12.8% of the Hong Kong population suffer from Post-Traumatic Stress Syndrome. COVID-19 stressors increased levels of anxiety and depression during the pandemic. Hong Kong is an overworked city with 61% of its population being stressed out, anxious, depressed, and in a bad mood. Occupational stress adds an annual economic cost to the city of HK$4.81-7.09 billion. “Positive emotions buffer the negative impact of job stressors on absenteeism” (Siu et al., 2020), but the mental-care system is overburdened. We should “encourage and promote early health seeking treatment…” (Hung et al., 2022), but care avoidance is common. “Psychological support, such as brief, home-based psychological interventions, should be provided to citizens…” (Choi et al., 2020), but these are absent in Hong Kong.

We propose training Social Robots with Embedded Large Language Models (LLMs) on localised, cultural, and personal data to bring customised mental care to those who remain undetected by the official medical care system. Human-like social robots have shown to be natural interaction partners, assisting information search, improving health and mental wellbeing, and supporting educational tasks. We will connect robots and avatars to the Hong Kong CityNet (HK CityNet) established under the 2020/21 Theme-based Research Scheme (TRS) project, while providing a new software architecture for distributed computing, scalability, and privacy protection. We will develop training protocols, logic-symbolic artificial intelligence (AI), and design guidelines for novel methods and functionality, tested on-site by local communities.

Tasks to be performed under this project include: 1) Building an architecture for dynamic access to the HK CityNet with large-scale deployment of health-related information while handling Cloud delays, scalability issues, mobile distributed Internet of Things, and data privacy; 2) Developing AI to continuously monitor topics citizens worry about and train LLMs on the most relevant topics, using HK CityNet information; 3) Refining LLMs with logics, norms, and values (medical, cultural) to prevent improper conduct and hallucinating ‘facts’; 4) Developing localised and personalised conversation formats for topics citizens worry about; and 5) Evaluating performance and efficacy through field studies into local communities.

The uniqueness and novelty of this project lie in cutting-edge technology guided by design studies into urban dynamics. We target information relevant to citizens and take care that AI-enhanced information provision prioritises the role of emotions in technology use, avoiding market failure of apps and large-scale Information and Communications Technology (ICT) infrastructure.