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Theme-based Research Scheme - Second Round Layman Summaries of Projects Funded

Theme 1: Promoting Good Health
Project Title: Functional analyses of how genomic variation affects personal risk for degenerative skeletal disorders
Project Coordinator: Prof Kathryn S.E. Cheah (HKU)

Abstract
Intervertebral disc disease (IDD) leads to low back pain, thence to disability and suffering. It is a complex ageing disorder compounded by both environmental and genetic factors. In IDD the mechanical strength and shock-absorbing capacity of the disc decrease and the consequential structural failure leads to disability. But the underlying etiology is poorly understood, hampering the development of therapies. It has been established that all the cell types in the nucleus pulposus (NP) of the intervertebral disc (IVD), are derived from a common notochordal precursor. The inverse correlation between development of IDD and the presence of notochord-like cells in the NP leads to the hypothesis that their persistence is protective. But the process by which the notochord cells give rise to the cells in the NP and the controls involved are poorly understood. IDD has an estimated heritability of up to 74%, yet only a few genetic risk factors have been found. We and others have identified a few genes that contribute modest risk for IDD; many more genetic risk factors remain to be discovered. The challenges are to define the functional attributes of the genetic factors associated with IDD. We ask how does genomic variation contribute to disease risk, onset, severity and progression? We hypothesize that variations in the regulation of genes and proteins modulate the onset, progression and severity of IDD and that maintaining NP cell function plays a critical role in the process.

As an internationally recognized leading multidisciplinary team of clinicians and scientists with a successful history of collaboration, we will address this by building on: a) knowledge of the genomic biology of the human and mouse intervertebral disc and b) our research on a HK population-based cohort, one of the world's largest, comprising 3500 individuals collected over a decade, with DNA samples, spine MRI scans, demographic and clinical information. We aim to understand the processes by which embryonic notochordal cells progress to the mature cell types in the adult NP, followed by their decline in IDD. We will obtain, correlate and integrate data from long-term longitudinal follow-up with identification of i) changes in regulators of gene expression in degenerating human NP cells; ii) rare gene variants. We will identify key factors for the maintenance of NP cells. We will establish protocols for differentiating NP cells from pluripotent stem cells, for expanding and maintaining them and for performing functional tests of disc cells.

From this research we will have deepened knowledge of the systems biology of disc degeneration and the signaling pathways responsible for maintaining a healthy disc; assessed the functional impact of putative genetic risk factors and gained phenotype-genotype insight with implications for prognosis. By integrating this knowledge with clinical and environmental factors, we will be able to predict total personal risk for IDD that will improve prevention and disease management. IDD cannot be treated by drugs and current cell-based therapies face considerable hurdles. Long-term applications include design of improved cell-based therapies and/or non-invasive approaches, according to personalized genetic risk, to protect healthy discs from degeneration and retard or reverse the degenerative process.


Theme 1: Promoting Good Health
Project Title: Stem Cell Strategy for Nervous System Disorders
Project Coordinator: Prof Nancy Y Ip (HKUST)

Abstract
There is an urgent need for therapies that can effectively alleviate the devastating effects of neurological diseases. Effective treatments are either lacking or limited resulting in enormous economic and social challenges to patients, their families, and society as a whole. A rapidly aging global population further threatens to propel the current situation to catastrophic proportions. Hong Kong, like other developed countries and regions, will thus have to deal with an overburdened medical system. Therefore, it is essential to establish focused research programs aimed at furthering our knowledge of the nervous system and enabling new treatments and cures for neurological diseases.

Regenerative medicine is a young, dynamic, and rapidly growing field, and recent breakthroughs show much promise in the development of effective neural stem cell-based therapies that replace lost or damaged brain cells or induce self-repair within the brain. However, understanding the intricate interplay of signaling molecules as well as intrinsic and extrinsic factors in the generation and differentiation of neural stem cells are imperative before any clinically effective therapy can be developed.

The proposed project aims to lay the essential groundwork for the development of neural stem cell-based regenerative treatments by taking two complementary approaches - basic research and translational research. In basic research, we will first investigate the regulatory processes underlying neurogenesis, the process by which new brain cells are generated. Using embryonic neurogenesis as the model system, we aim to elucidate the regulatory mechanism that controls the balance between proliferation and differentiation of neural stem cells with a specific focus on understanding the molecular basis governing asymmetric cell division, a fundamental step for generating new brain cells during neurogenesis. We will also investigate the intrinsic machinery that regulates the differentiation and maturation of newborn neurons, and their eventual integration into neural networks. Once these signaling molecules/pathways are identified, their therapeutic efficacies will be verified in cell-based and animal models. Furthermore, in translational research, we will leverage our proven expertise in traditional Chinese medicine-based drug discovery. Utilizing novel extraction methodologies and proprietary cell-based assays and animal models, we aim to identify agents (small molecules/TCM extracts) that possess neurogenic activities. This approach is highly feasible and rewarding as the team has already successfully obtained several neurogenic lead compounds from TCM.

This project provides crucial groundwork for development of novel therapies that could effectively reverse the devastating effects of neurological and psychiatric disorders, thereby enhancing the quality of lives of millions of people worldwide. The work outlined in this proposal will contribute to the development of advanced research techniques, provision of training opportunities for young scientists, and strengthening collaborative ties among institutions in Hong Kong, the Mainland, and abroad. It will also enhance Hong Kong's developing biopharmaceutical industry by highlighting the territory's excellent scientific research capabilities, infrastructure, and access to a highly skilled work force, while placing Hong Kong on the map for advanced research in neural regenerative medicine.


Theme 2: Developing a Sustainable Environment
Project Title: Sustainable Lighting Technology: From Devices to Systems
Project Coordinator: Prof Ron Shu Yuen Hui (HKU)

Abstract
"Built environment" generally refers to the man-made surroundings and their infrastructures for human activities. Its definition for surroundings ranges from homes, buildings and neighborhoods to cities, and for infrastructure from air-conditioning in buildings to large-scale networks such as road networks and street lighting systems. Sustainability in this context refers to the ability to endure and is related to recyclability of materials, reduction of waste and energy usage.

Lighting systems consume about 20% of global electrical power and their control circuits have been identified as one of the major sources of electronic waste. With the recent revolution of LED technology, new LED devices with much improved luminous efficiency and lifetime are now commercially available. They are also expected to replace energy-inefficient incandescent lamps and mercury-based fluorescent lamps in the future. LED technology actually involves several technical aspects, including (i) LED Devices, (ii) LED Drivers, (iii) Power Control and (iv) Thermal Design of Lighting Fixtures. While LED technology has successfully found applications in decorative, signaling, display and signage applications, it is still not widespread in public lighting applications. With continuous progress in LED "devices", recent creditable research highlights that the actual bottlenecks of LED technology in public lighting lie in the "system" aspects. The lifetime of an LED "system", for example, is limited not by the lifetime of the LED "devices" (typically 80,000 hours), but by the that of the electrolytic capacitors (typically 8,000 hours) in conventional LED drivers. The bottleneck of the "System" aspects of LED technology has been severe enough that led to a special industrial session by LED manufacturers in the IEEE Applied Power Electronics Conference to address the systems reliability issues in February 2012.

This proposal is related to the "sustainability" of lighting systems (used in buildings and cities' large-scale infrastructures such as road lighting) that consume 20% of electricity globally. Sustainable Lighting Technology proposed here deviates from the traditional Energy-Star concept which focuses only on energy saving. It stresses a new principle that includes (i) energy saving, (ii) long product lifetime and (iii) recyclability of product materials. It highlights the important point that "energy-saving technology is not necessarily environmentally-friendly if it generates lots of harmful electronic waste within a short product lifetime".

This proposal involves a new investigation into a new General LED System Theory for "multiple non-identical" Solid-State LED devices. By linking LED "device" theory to "system" theory, novel LED systems with not only high energy efficiency and luminous efficacy, but also lifetime exceeding 10 years and over 80% product materials recyclable will be studied and developed. The project will focus on an "integrated system approach" that covers (i) new white LED device structures and manufacturing processes, (ii) novel passive and active LED drivers and control techniques including both power and color control, (iii) current balancing techniques, (iv) novel device geometrically-staggered distribution and thermal designs and (v) a new generation of self-cooling heatsinks, so that future LED systems can meet the three sustainability criteria.

This project is expected to lead to both theoretical & practical breakthroughs. The outcomes of this proposal are expected to include (1) a novel Generalized LED System Theory for "multiple non-identical" LED devices, (2) new LED device structure with improved thermal management, (3) the generalization and classification of LED driver topologies with long lifetime, (4) a new design methodology & tool for optimization of a new generation of highly efficient and sustainable lighting systems, and (5) practical realization of the new "Sustainable Lighting" principle that can replace traditional "Energy-Star" concept with the aim of drastically reducing electronic waste worldwide. With several major lighting research centers already based in Hong Kong and over 1000 LED product manufacturers in South China, this project will bring significant benefits to Hong Kong and its nearby regions. Apart from the potential contributions made to industry, this project will involve training of research students.


Theme 2: Developing a Sustainable Environment
Project Title: Cost-effective and eco-friendly LED system-on-a-chip (SoC)
Project Coordinator: Prof Kei May Lau (HKUST)

Abstract
Broader Impact to Hong Kong - In August 2011, the Hong Kong government launched a public consultation on restricting the sale of energy-inefficient incandescent light bulbs (ILB), based on the overseas experience in the past few years (www.enb.gov.hk/bulbs_consult.html). The consultation ended in November 2011 with many supportive responses. An estimated annual reduction of electricity consumption by up to 390 GWh, or HK$390 million saving in electricity bill assuming a tariff of $1 per kWh annually, and a reduction in carbon emission by 273,000 tons is achievable. As part of its energy savings initiative for a sustainable environment, HK needs to become an active participant in this endeavor. The current solution of energy-efficient light-bulbs (EELB) using compact fluorescent lights (CFL) posts environmental concerns if the ban of ILB is in full effect. As an alternative to CFL, we should play an active role in the Solid-State Lighting (SSL) revolution that has gone into full swing worldwide. On a broader level, our mission is to accelerate the adoption of the eco-friendly SSL in HK and the world by unleashing the intrinsic LED efficacy with innovative device fabrication and packaging technologies. With the embedded integrated circuits in our proposed microsystems, we will significantly improve the efficacy of LED-based lighting sources. As such, our technology provides both the environmental and commercial incentives that hasten the transition to an LED-lighted world. A generation of multidisciplinary researchers will be trained and possibly new ventures will be spawned, contributing to the transformation of Hong Kong to a knowledge-based economy.

Intellectual Merit - Through decades of research and development, semiconductor-based light emitting diodes (LEDs) have taken great leaps in performance (efficacy >200 lm/W in labs and >100 lm/W for commercially available LEDs) and manufacturing yield. However, the adoption rate is still slower than previously projected as the general public is yet to be convinced that the higher initial cost of LED lighting makes economic sense. Unfortunately, the environmentally friendly nature of LEDs over the mercury-containing fluorescent lights was not a sufficient reason for switching, added to the unfavorable consumer experience of unreliable LED products flooding the market. Technically speaking, the GaN-based LED is the light source of choice for SSL because of its high efficiency, stable nature and maturing technology. Despite the popularity of GaN-based LEDs, their current status is similar to the transistors in the 1950s. Most LED chips are individually or group packaged and used as a small light source. Poor package designs for thermal management, optics and electrical drive systems resulting in significant loss have impacted the realization of the inherent LED performance, misleading consumers about the true efficacy and reliability of LED products. One of our goals is to overcome this barrier by utilizing silicon IC technologies in LED lighting and develop an integrated optimization from device design to lighting systems. In parallel, our integrated approach will also enable novel optical wireless applications while decreasing system form factor and total cost of ownership with increased reliability. To lower the manufacturing cost, our platform will focus on novel direct growth of LEDs on silicon wafers to allow for high volume production (on 300mm wafers) leveraging the mature Si IC technology with the cost advantages of CMOS scaling. This is a major intellectual challenge given the huge differences in material properties between GaN and Si. Ideally, integration of all the components on a Si platform is the dream of all the electronic communities involved.

World-class Interdisciplinary Team - With world-renowned material scientists on our team and building on our past successes, we have significant advantages in realizing the vision of bringing "better light for better living" to Hong Kong and the world. Our holistic approach (materials + device + circuit + systems) has fostered the assembly of the world's premiere system and integrated circuit design experts on the same team. By working together in a synergistic manner under the LED theme, we have systematically engineered a set of interdisciplinary projects, with special emphasis on solving the "technology interface" challenges, to achieve our mission.


Theme 3: Enhancing Hong Kong's Strategic Position as a Regional and International Business Centre
Project Title: Enhancing Hong Kong's Future as a Leading International Financial Centre
Project Coordinator: Prof Douglas W Arner (HKU)

Abstract
By the end of the 20th century, Hong Kong had emerged as one of the world's major international financial centres. Today, while finance remains central to Hong Kong's future, it is facing unprecedented challenges, both in China and globally. In the context of China, the continuing process of economic reform and financial development raises many opportunities but at the same time brings into question Hong Kong's traditional role as the primary intermediary between China and the global financial system. At the same time, the global and European financial crises have raised fundamental questions about finance, exchange rate systems, the global position of China, and the future role of the renminbi, including Hong Kong's role therein. Reflecting the centrality of finance to Hong Kong, Article 109 of the Hong Kong Basic Law, ascribes the Hong Kong Government an obligation "to provide an appropriate economic and legal environment for the maintenance of the status of Hong Kong as an international financial centre." However, it has yet to take a comprehensive approach to this obligation or to consider its strategic and practical implications. This project, built around a team of internationally recognized experts from economics / finance, geography, law, and international relations, will analyze the elements required not only to maintain, but also enhance, Hong Kong's future as an international financial centre, focusing on its role in China's ongoing financial liberalization and economic development.