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ANR/RGC Joint Research Scheme - Layman Summaries of Projects Funded in 2012/13 Exercise

Development of Point-of-Care Diagnostic Tools Based on the Conformational Switch of Oligonucleotides

Hong Kong Principal Investigator: Dr. Dik-Lung MA (Hong Kong Baptist University)
Mainland Principal Investigator: Dr. Jean-Louis MERGNY (Universite Bordeaux Segalen)

Mutations in the genetic information of an organism can lead to the aberrant production of gene products. In humans, such genetic abnormalities can contribute to the development of various diseases. One type of DNA mutation is gene deletion, where a section of DNA or an entire part of a chromosome is missing. Some mutations can lead to genetic diseases characterized by elevated concentrations of biomarkers, which are usually proteins with critical roles in regulating cellular processes. The aberrant activity of such biomarkers has been implicated in the development of a number of diseases, including cancer, developmental disorders and inflammation. Due to the importance of mutated DNA and biomarkers as indicators and causative agents of diseases, the highly sensitive and efficient detection of biomarker molecules and mutant DNA are of paramount importance for the early monitoring and therefore prevention and/or treatment of genetic diseases.

The development of small and portable probe for point-of-care diagnosis has emerged as a critical issue in in vitro diagnostics technology. To date, numerous methods have been developed for the selective detection of DNA, including the polymerase chain reaction (PCR) and rolling cycle amplification (RCA). However, these methods tend to be time-consuming, and involve tedious sample preparation and/or complex operation. For protein biomarker detection, the most commonly-used techniques include enzyme-linked immunosorbent assays (ELISA), capillary electrophoresis (CE), and mass spectrometry (MS). However, these detection methods typically involve multiple sample preparation steps and/or expensive instrumentation. Most importantly, the aforementioned methods for DNA and biomarker detection generally require off-site laboratory equipment, and are not amenable to real-time point-of-care analysis.

We propose to develop oligonucleotide-based sensing platforms for the detection of DNA mutations and protein biomarkers, including those related to diseases such as cancer and inflammation. Utilizing the high fluorescence response of labeled oligonucleotides, or the long phosphorescence lifetimes of transition metal complexes, we envision that our methodology could be adapted for the in vitro detection of disease-related biomarkers in biological media such as human cellular and nuclear extracts. In order to maximize the selectivity, sensitivity and response time of our test, we will rigorously optimize the DNA sequence and the experimental parameters of the proposed assay. Our proposed methodologies are highly simple, sensitive, rapid, selective, low-cost and amenable to real-time and high-throughput analysis. We anticipate that the proposed technology could be highly useful to both academic and biomedical researchers worldwide working in the fields of medical diagnostics or biomarker biochemistry, and could be potentially applied for the "on-site" clinical diagnosis of human diseases.

Coordination and Computation in Distributed Intelligent MEMS

Hong Kong Principal Investigator: Prof Jiannong Cao (The Hong Kong Polytechnic University)
Mainland Principal Investigator: Prof Julien Bourgeois (FEMTO-ST Institute)

Microelectromechanical systems (MEMS) have reached a position of design maturity and are therefore ready for the mass-production of micro-scale devices. MEMS technology is present in the day-to-day life of people. Recent examples of mass-produced MEMS include accelerometers, inertial measurement unit (IMU), and digital micromirror device (DMD), etc. The advantages of MEMS are the small forms, low costs when mass-produced and, for some applications, different reaction than macro systems to physics law. MEMS can be used either as single elements (accelerometers, IMU) or they can be grouped and can act together to reach a global goal (DMD). The latter is called distributed MEMS. Due to their small size, their low-cost and the fact that they can be mass-produced, millions of units can be used in a very small space. For example, a volume of less than 1 m3 of 1mm-diameter silicon balls has an equivalent number of nodes than in internet.
Past challenges focused on the engineering process of MEMS, but future challenges will consist in adding embedded intelligence to MEMS systems, so that they will be able to collaborate efficiently. A possible approach to dealing with the challenge is to add processing capacity linked to the distributed MEMS. The processing unit can be centralized on a PC or on an FPGA, but this limits the scalability of the system. A distributed architecture solves these problems. The use of the expression "distributed intelligent MEMS" has been suggested. Distributed intelligent MEMS systems will be composed of thousands or even millions of systems which will raise new scientific challenges both for controlling and for programming such large ensembles. Managing this scalability requires paradigm-shifts both in hardware and software parts. Furthermore, the need for actuated synchronization, programming, communication and mobility management raises new challenges in both control and programming. Finally, MEMS are prone to faulty behaviors as they are mechanical systems and they are issued from a batch fabrication process. A new programming paradigm which can meet these challenges is therefore needed. In this project, we propose to develop CO2Dim, which standards for Coordination and Computation in Distributed Intelligent MEMS. CO2Dim is a new programming paradigm based on a joint development of programming and control capabilities so that actuated synchronization can easily be programmed and can scale up to millions of units. The main topics to be investigated include fault detection in distributed MEMS, K-simultaneous consensus in asynchronous message passing systems, distributed cooperation of distributed MEMS components, and rogramming models and support for distributed MEMS applications.

New Approaches to the Mao Era (1949-1976): Everyday History and Unofficial Memory

HK Principal Investigator: Prof Frank Dikotter (The University of Hong Kong)
French Principal Investigator: Dr. Sebastian Veg (French Centre for Research on Contemporary China)

Much of the research published on the Mao era - the early 1950s, the Anti-Rightist movement, the Great Leap Forward and the famine, the Cultural Revolution - relies overly on Party sources and various types of internal but nonetheless official publications. Archives are difficult to access and first-hand accounts are often skewed, providing little information about the everyday lives of ordinary people. In recent years, there has been a slight opening of archival sources, and in parallel, a significant development of oral history projects in China, as the generations of first-hand witnesses of Maoism reach old age. They open a fruitful realm for new research, both on everyday society under Maoism as a historiographical object and on the way Maoism is remembered by ordinary people. These two components - the documentation of history and the preservation of memory - are inseparable in the emergence of a critical history of Maoism.
We propose to investigate various aspects of this field, ranging from new archives and oral histories of everyday life under Mao, in particular the violence that characterized social relations at the time, to the contemporary efforts devoted to preserving a non-official memory of Maoism. These efforts call into question the Party's monopoly on writing the history of the People's Republic. While some of the "memorial" activities developed by former Rightists or Educated Youths are nostalgic and generally uncritical, many other forms of association and sociability are based on the desire to critically confront the past, using the tools of research and historiography, in order to build a "popular" or "unofficial" (minjian) history of post-1949 China.
This project relies on ongoing work by the researchers involved, including Frank Dikötter's recent book Mao's Great Famine, Wang Aihe's investigation of a group of underground artists during the Cultural Revolution, Michel Bonnin's study Lost Generation based on extensive interviews with former sent-down Educated Youths, Jean-Philippe Béja's investigation of several citizen history associations in China and their significance for the civil rights movement (weiquan yundong), and Sebastian Veg's work on how ordinary memories of the Anti-Rightist movement are documented in literary works and independent documentary films.

Phosphorus-Containing π-Conjugated Molecular Materials - Design, Synthesis and Their Supramolecular Assembly for Light-Emitting, Light-Harvesting, Electronic Communication and Charge Transport Functions

HK Principal Investigator: Prof Vivian Yam (The University of Hong Kong)
French Principal Investigator: Prof Regis Reau (The University of Rennes 1)

Functional materials research is one of the top priority strategic areas of development in science and technology of the century. The rational design and synthesis of molecular materials have attracted growing attention owing to their enormous and unpredictable potentials in molecular devices, especially in the development of molecular optoelectronics and electronics. Research in π-conjugated organic molecular materials is currently a rich and proliferating field in molecular materials research. Recently there has been a growing interest in the incorporation of heteroatoms in π-conjugated molecular materials, especially those involving nitrogen and sulfur heterocycles. While nitrogen and sulfur heterocycles, such as carbazoles and thiophenes, have been increasingly employed as building blocks in the synthesis of molecular materials for organic optoelectronics and electronics, especially in organic thin film transistors (OTFTs) and organic photovoltaics (OPVs), much less attention has been focused on the corresponding synthetically more challenging but electronically interesting phosphorus-containing heterocyclic counterparts (e.g. phospholes) and derivatives. One key property of these phosphorus subunits is the versatile reactivity of the P-centre, allowing structural diversity to be readily generated. In this project, the design, synthesis and supramolecular assembly of phosphorus-containing π-conjugated molecules and their metal-containing derivatives will be explored. An understanding and control of supramolecular assembly will help to direct and organize the π-conjugated systems for optoelectronic and electronic functions. These molecular materials will be characterized, and their electronic absorption, photoluminescence and electrochemistry studied. These will provide useful information on the excited state energy, tuning of their bandgap energy, and their electronic communication and charge transport properties. Computation studies will be performed to provide insights into their bonding, structure, excited state energy and redox chemistry. The light-harvesting behaviour will be explored. Efforts will be made to fabricate organic light emitting diodes (OLEDs) and OPVs using selected molecular materials and to study their device properties. It is envisaged that the project will lead to the discovery of novel classes of phosphorus-containing π-conjugated molecular materials and assemblies with functional properties and an understanding of their structure-property relationships. It is believed that these phosphorus-containing molecular materials hold great promise in advancing this field of research since their incorporation and coordination to transition metal centres and their supramolecular assemblies may lead to systems with unique optical, luminescence and electronic properties that may find applications as light-emitting and light-harvesting materials in molecular optoelectronics (OLEDs and OPVs), and as molecular wires for electronic communication and charge transport in molecular electronics.