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RGC Collaborative Research Fund - Layman Summaries of Projects Funded in 2010/2011 Exercise

High Precision Measurement of Neutrino Oscillation at Daya Bay
Project Coordinator: Prof Ming Chung Chu (CUHK)

The recent discovery of neutrino oscillation -a neutrino travelling in space transforms from one type to another - has profound impacts on particle physics, astrophysics and cosmology. The Daya Bay Reactor Neutrino Oscillation Experiment aims to measure a key but yet unknown neutrino oscillation parameter, θ13, to an unprecedented precision of better than 3 degrees, which is critical to the design of future experimental tests of a possible explanation of why matter dominates anti-matter in the universe, a key condition for our existence.

The Hong Kong team has been an active member of the Daya Bay Collaboration, an international team with 38 institutions. We will contribute to the commissioning and monitoring of the experiment and analysis of data, with the help of a subsystem of the antineutrino detector built by our team. We will also design and construct a continuous radon monitoring system as well as a cover gas system to minimize radon contamination of the detectors.

Schematic Identification of Predictors of Treatment Non-Responders in Patients with Systolic Heart Failure
Project Coordinator: Prof Cheuk Man Yu (CUHK)

Chronic heart failure (CHF) is a major public health problem in Hong Kong. Data from our heart failure registry shows that 1-year mortality and readmission for heart failure (HF) is about 50%. Over the past two decades there have been significant advances in the treatment of systolic heart failure with the use of drugs that block the major neurohormonal responses to the initial injury. Recently cardiac devices such as biventricular pacing (or CRT) which rectify the abnormal conduction and contraction in CHF have also been used for CHF treatment. Although large scale clinical trials have demonstrated the efficacy and safety of the commonly used drugs for CHF, it is a common clinical observation that not all patients respond as well as others and some not at all. Our hypothesis is in that myocardial fibrosis and inflammation are key mediators of non-response to CHF treatment. We wish to undertake a large scale project to attempt to estimate the prevalence of non-response and how can we identify these patients. We will combine the use of advanced echocardiographic imaging techniques and novel biochemical and molecular (microRNAs) biomarkers to establish and validate an Assessment Model which identify treatment non-responders. Cardiac MRI will also be performed in a subgroup to determine the relationship between cardiac scar burden and echocardiographic function. The project also has the potential of identifying new diagnostic and prognostic markers for CHF (biomarkers and microRNA), pioneer new approaches to manage CHF, as well as geared towards the development of new treatment targets.

Identification of Redox-sensitive Proteins and Characterization of Their Functions in Regulating the Oxidative Stress Response in Arabidopsis
Project Coordinator: Dr Yiji Xia (HKBU)

Cellular redox status regulates a variety of biological pathways. Oxidative stress is linked to various human diseases. Similarly, cellular redox homeostasis is a common mediator of physiological responses to environmental stresses in plants. Oxidative stress signals are sensed by redox-sensitive proteins which then transduce the signals into physiological responses. We will develop redox proteomics approaches to identify redox-sensitive proteins in the model plant Arabidopsis and investigate their functions in regulating physiological responses to oxidative stress conditions. The knowledge from the study will be greatly helpful in improving crop productivity. The redox proteomics technology platform developed from the proposed research can also be applied to similar studies in other organisms including humans.

Mass spectrometry-based metabolomics for the characterization of cellular metabolic pathways associated with the development of hepatocellular carcinoma
Project Coordinator: Prof Zongwei Cai (HKBU)

We will develop and apply mass spectrometry (MS)-based metabolomics for investigating hepatocellular carcinoma (HCC) that is one of the common diseases posing major threat on human health in Hong Kong. Systems-level metabolic profiling of different cell lines will be analyzed for deciphering the functions of eIF-5A2 and PDSS2. Furthermore, cancer stem cells (CSCs) will also be investigated by metabolomic approach. The use of CSCs marked by CD133 surface phenotype and bearing features would provide new insight for metabolic programming associated with HCC development. The differentiating metabolites will be highlighted and identified to localize the metabolic pathways associated with HCC development by using non-targeted and targeted metabolomic approaches. For the validation, analytical techniques will be applied for the determination of enzymatic mutations or abnormally enzymatic activities in cancer cell lines. The metabolic networks will be simulated for opening a novel systemic insight into the development of HCC.

Development of efficient luminogenic materials in the aggregate state: fundamental understanding and practical applications
Project Coordinator: Prof Ben Zhong Tang (HKUST)

The development of new light-emitting materials has allowed us to gain new knowledge of the world around us by opening a new avenue to scientific achievement and societal development. Thanks to the enthusiastic efforts of scientists, a large number of luminescent molecules have been prepared. These materials emit intense light in solutions but they emit weakly or even not at all in the solid state. This problem must be solved because for most real-world applications, luminescent materials are used as solid films. In this project, we discovered the phenomenon of aggregation-induced emission in some molecules. These materials show stronger emissions in the solid state than in solutions. We identified its cause, based on which, we prepared diverse materials, ranging from small molecules, to organometallic complexes, to high-molecular weight polymers. We explored their high-technological applications as fluorescent chemosensors for as example explosives, as biological probes for imaging, diagnosis and therapy, and as solid-state emitters for organic light-emitting diodes.

Protein-phosphoinositides Interactions in Neuronal Signaling
Project Coordinator: Prof Mingjie Zhang (HKUST)

Phosphoinositides (PIPs) are important signaling lipids that are distributed in various cellular membranes. PIPs, via binding to proteins, actively regulate numerous cellular processes. In this project, we will continue to investigate the structures and functions of a series of protein-lipid interactions that are implicated in both normal functions as well as the etiology of brain and heart muscle cells. We aim to elucidate the biochemical and structural basis of the interactions between PIPs and these proteins and to uncover the physiological significance of these newly identified protein-lipid interactions. The outcome of this project is expected to make important contributions in understanding a number of human diseases including neurodegenerative diseases and cancers.

Programming the Second Generation Tumor-targeting Bacteria
Project Coordinator: Dr Jiandong Huang (HKU)

Cancer remains a leading cause of death with current therapeutic methods. Novel therapies are therefore in urgent needs. One potential method is to use bacteria as cancer therapeutic agent. Since bacteria can sense their environment, distinguish between cell types, synthesize and deliver drugs into cancer cells, attempts are made to program bacteria to attack tumors. Current advances in synthetic biology technology offer great opportunities in refining this approach. In this project, we will establish a stepwise approach to program bacterial strains that are able to detect tumor microenvironment, effective in killing cancer cells and safe to normal tissues, so that they can ultimately be used clinically to treat cancer patients.

A Multi-disciplinary Approach to Investigate Vascular Dysfunction in Obesity and Diabetes: From Molecular Mechanism to Therapeutic Intervention
Project Coordinator: Dr Aimin Xu (HKU)

Cardiovascular disease (CVD), including stroke, heart attack and periphery artery disease, is the major cause of death and hospitalization in the ageing population worldwide. Much of the high incidence of CVD is attributed to the epidemic of obesity and diabetes. Unfortunately, none of the current therapies can reverse the progression of CVD. To develop more effective medications, it is of great importance to understand the pathological pathways that link obesity, diabetes and vascular disease. With the support from our previous RGC Collaborative Research Fund (CRF), we have identified three fat-derived circulating factors as a key mediator of obesity-related CVD in mice. The objective of this collaborative project is to comprehensively investigate the pathological roles and clinical relevance of these circulating factors in the development of CVD in both large animals and humans. The results will help us to develop new diagnostic tools and better therapeutics for risk prediction and prevention of CVD.

Self-Assembled Synthetic Ion Channels: Design, Characterization and Biomedical Applications
Project Coordinator: Prof Dan Yang (HKU)

Ion transport across membranes in cells is controlled by ion channel proteins. Dysfunction of ion channels has been associated with many severe human diseases such as cystic fibrosis, asthma, hypertension, epilepsy and myocardial infarction. Therefore, developing drugs that modulate the functions of ion channels or regulate ion transport have received significant attentions in pharmaceutical industry.
In our previous research work supported by RGC Competitive Earmarked Research Grants (CERG) (HKU7367/03M) and RGC Collaborative Research Fund (CRF) (HKU 2/06C), we have discovered a novel class of small molecules that self-assemble in the lipid membranes of living cells into synthetic chloride channels, which increase chloride conductance in human epithelial cells, modulate membrane potentials, and even can initiate relaxation of smooth muscles.
In this proposed research, we plan to continue our inter-disciplinary collaborations by combining the expertise in chemistry, physiology, cardiology and pharmacology to discover synthetic ion channels that selectively transport small anions or cations across biological membranes and explore their potential biomedical applications in the treatment of human diseases associated with channel dysfunction, such as cystic fibrosis, asthma, hypertension, and myocardial infarction.

Smart Grid
Project Coordinator: Prof Victor On Kwok Li (HKU)

Concerns with global warming prompted governments throughout the world to pursue policies aiming at increasing renewable energy generation so as to reduce greenhouse gases due to electricity generation with fossil fuels. However, due to the intermittent characteristics of renewable energy sources such as wind and solar, it is a challenge for a system with large renewable generation capacities to implement real-time power balance. Recently, many countries have announced smart grid research programs to re-vitalize their electricity generation and distribution infrastructures using modern technologies such as communication network, sensor network, power electronics, and control technologies to manage the power grid more effectively, and to cope with such complexities as fluctuating energy sources and consumption. The key objective of this proposed project is the integration of information technologies and electric energy generation and distribution technologies to design innovative means to manage and control the electricity generation and distribution network. A novel hybrid simulation laboratory will be built to test our research results in innovative designs for efficient communication, computing and control of smart grids.