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

Theme 1: Promoting Good Health
Project Title: Systematic Development of Molecular Targets for Nasopharyngeal Carcinoma
Project Coordinator: Professor Kwok-wai Lo (CUHK)

The distinct occurrence and highest global incidence of Nasopharyngeal Carcinoma (NPC) in South China has crowned this deadly malignancy as the "Cantonese Cancer". NPC is a major health-care problem in Hong Kong, where it is also the most prevalent cancer in our middle-aged workforce population. Despite advances in current radio-chemotherapy, poor clinical outcome remains the major concern in >60% of newly diagnosed NPC patients, who are usually presented with advanced stage disease. The key problems of these patients are distant failure and lack of efficient treatment for recurrent diseases. New clinical interventions to treat the disease, prolong disease-free survival and improve quality of life of patients are therefore of strategic importance.

A comprehensive understanding of genetic changes involved in NPC tumorigenesis is expected to offer the basis for research to develop promising disease control strategies for this cancer. Systematic discovering driver genetic lesions and apprehending how they contribute to transformation and progression of NPC are essential information to underpin reliable biomarkers and novel molecular targets for therapy; the cornerstone of developing patient-specific personalized medicine. In this application, we propose to decode the DNA sequence of entire NPC genome and thereby catalogue the whole spectrum of genomic changes involved in NPC tumorigenesis by massive parallel genome sequencing. Our team will systematically define the driver mutations and identify key "molecular targets" through large-scale whole genome and transcriptome sequencing, bioinformatic analysis and extensive validation in microdissected primary NPC samples using our newly developed technologies. Functional studies will confirm the oncogenic activities and biological significances of candidate driver mutations. To translate the genomic findings to specific NPC biomarkers, statistical analysis will be conducted to determine the clinical correlation between somatic variants and patients' clinical outcome. Importantly, candidate molecular targets and relevant tumour dependency can be elucidated for their therapeutic potentials in our unique panel of in vitro and in vivo NPC models. The finding will provide important novel biomarkers and therapeutic targets for developing personalized cancer treatment strategies. We expect this project would make strategic breakthrough in molecular genetics of NPC and contribute significant impact to the control of this common cancer.

Theme 1: Promoting Good Health
Project Title: An Integrated Trans-omics Approach to Diabetic Cardio-renal Complications: From Novel Discoveries to Personalized Medicine
Project Coordinator: Professor Ching-wan Ronald Ma (CUHK)

Diabetes is a major health problem worldwide, including in Hong Kong. Most of the healthcare burden from diabetes is associated with the management of diabetic complications, in particular, cardiovascular and renal complications. Diabetes is the major cause of end-stage renal disease (ESRD), and increases the risk of cardiovascular disease (CVD) by 3-4 fold. Asian patients with type 2 diabetes (T2D) are particularly prone to renal complications when compared to patients of European origin. Only few genetic markers have so far been identified to predict diabetic cardiovascular-renal complications. Discovery of novel genetic or other biomarkers for diabetic complications can help identify at risk subjects for intensive risk factors management, advance our understanding of disease pathogenesis, revolutionize care and provide novel targets for drug development. In this Grand Challenge, we aim to utilize the unique resource from the Hong Kong Diabetes Registry, with more than 10,000 patients with T2D with detailed biochemical assessment of risk factors and documentation of medication history, who have been prospectively followed up for a mean duration of 8 years, with an accrual of 4,000 events of cardiovascular and renal complications. We will utilize a multi-omic approach and use new-generation sequencing (NGS) and other technologies to conduct a comprehensive evaluation of the genome, epigenome and transcriptome of diabetic patients with complications and diabetic patients free of complications despite long duration of disease. We will utilize advanced bioinformatics analysis to integrate findings from these different approaches. Insights from this multi-faceted investigation will be compared to findings from animal models of diabetic complications. We will use bioinformatics, in vitro experiments and animal models to characterize the functional significance and regulatory pathways of novel genes identified from the genomic studies. In addition to novel biological discoveries, we aim to translate our findings and examine the clinical significance of these novel biomarkers, as well as their interactions with different treatments on disease outcomes. Finally, we will leverage on the existing healthcare infrastructure and detailed clinical information available to establish an expanded diabetes registry and biobank with contribution from major diabetes centres across Hong Kong for large-scale replication of any novel biomarkers discovered. This resource will be a first-of-its-kind. In sum, the translation of our genomic discoveries to clinical care will consolidate Hong Kong as a centre for innovative biomedical research and chronic care excellence.

Theme 2: Developing a Sustainable Environment
Project Title: Smart Solar Energy Harvesting, Storage, and Utilization
Project Coordinator: Professor Ching-ping Wong (CUHK)

The fast-growing demand for energy and the recognition of man-made global climate change underscore the urgency of developing clean and renewable energy resources to replace fossil fuels. Harvesting energy directly from sunlight by using photovoltaics (PV), photocatalysis, artificial photosynthesis, and other enabling technologies is a promising way to meet such requirements. As an alternative to conventional PV cells based on crystalline silicon wafer, vacuum-deposited CIGS and CZTS thin-film PV cells as well as solution-processed inorganic and organic thin-film PV cells offer processing advantages that will likely enable low-cost, high-throughput, and large-area PV production. Furthermore, the development of efficient and smart energy storage systems is imperative to effectively ensure reliable energy supply and increase the penetration of solar energy utilization. To sustainably utilize solar energy, intelligent power distribution grids need to be locally developed for solar energy generation, storage, and utilization at affordable cost and with enhanced security of supply through flexible transition between grid interconnected and islanded operating modes. All of these issues are in line with the strategic objectives on sustainable development outlined by the Hong Kong Government in 2005.

The proposed research scheme is aimed at the aforementioned strategic objectives through exploring various approaches in solar energy harvesting, storage, and utilization, to increase solar penetration to 10% in a selected campus building microgrid system under grid interconnected operation, and more importantly explore the feasibility of enhancing local security and independency of electricity supply of the microgrid through solar enabled islanded operation by end of 2017. The merit of this scheme lies in the fact that solar energy harvesting, storage, and utilization are holistically considered and thereafter they will be meticulously investigated. Accordingly the research topics covered by this scheme include: (1) the development of high-performance vacuum deposited thin-film PV devices and modules with new materials and processing techniques, particularly based on earth-abundant materials; (2) the establishment of an interdisciplinary research platform for fundamental research in solution-processed thin-film PV devices and modules based on inorganic and organic active materials, as well as the development of novel light-trapping schemes for efficiency enhancement; (3) the exploration of novel metal-oxides and organic dyes for chemical fuels production via artificial photosynthesis and photocatalysis; (4) the development of new materials and processing approaches for high energy-density batteries and supercapacitors, so as to realize a hybrid storage system; (5) the development of advanced strategies to integrate, manage, and control various subsystems based on information and communication technology (ICT) infrastructure and protocols, so as to enhance the performance and security of solar-enabled microgrids under various operating modes; (6) the practical demonstration of microgrid (MG) operations based on intelligent control and integration of PV modules, smart storages and loads and other technologies in a laboratory and selected campus building systems under interconnected and islanded modes.

Hong Kong has demonstrated its uniqueness and strengths in development of high-performance PV technologies, but not yet in the development of smart electricity storage and distributed grid systems. The proposed theme aims to strengthen the competitive edge of Hong Kong in solar energy technologies and their market penetration by combining the newly developed PV modules with the intelligent system integration. It is anticipated that the theme will not only create an interdisciplinary research platform for fundamental studies on solar energy harvesting, storage, and utilization, but also advocate applied research (e.g. development of flexible PVs) that leads to technology transfer to industry. The impact of the theme will be reflected in excellent R&D personnel training and generation of publications in leading journals, invited lectures at international conferences and intellectual properties that will benefit high-tech industry. All these will eventually lead to the formation of an area of excellence as well as to the substantial technology transfer of solar energy technologies in Hong Kong and beyond.