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ANR/RGC Joint Research Scheme - Layman Summaries of Projects Funded in 2017/18 Exercise

A-CUHK402/17
PACIfIC: Prevalence, characteristics and genetics of adherent-invasive Escherichia coli in Crohn’s disease patients: comparative study between France and Hong-Kong

Hong Kong Principal Investigator: Prof NG Siew-chien (The Chinese University of Hong Kong)
French Principal Investigator: Dr BUISSON Anthony (University of Auvergne)

Inflammatory bowel diseases (IBD), including Crohn's disease (CD), are contemporary conditions associated with westernization. Intestinal inflammation in CD arises from abnormal immune response to intestinal microbiota in genetically susceptible individuals.

Several groups have reported a higher prevalence of adherent invasive Escherichia coli (AIEC) in CD patients compared to healthy subjects and confirmed their pro-inflammatory potential. However, much of the work on this organism, and its potential role in CD, has been undertaken in areas of high CD incidence. For this organism to be considered truly implicated in CD, its presence in patients in other parts of the world needs to be demonstrated.

Hong Kong is amongst the top three countries/regions in Asia with the highest incidence of CD, which has increased by 30-fold in the past two decades. In addition, CD incidence varies between rural and urban area within China, with a higher incidence in urban areas, likely as the result of the influence of environmental factors including diet.

The main objective of this study is to assess the prevalence, characteristics and genetics of pathogenic AIEC in ileal CD across two different distinct populations and geography (Caucasians in France and Chinese in Hong-Kong) and to delineate therapeutics targeting AIEC in individuals with Crohn’s disease. These data will provide an improved understanding on whether AIEC is a risk factor for CD globally, the pathogenicity of AIEC and possible treatment based on AIEC eradication in CD which can lead to a personalized therapeutic case based approach in patients with CD.

A-HKU703/17
Electrically pumped GaN-based microdisk laser

Hong Kong Principal Investigator: Dr H.W. Choi (The University of Hong Kong)
French Principal Investigator: Dr Semond Fabrice (Centre de Recherche sur l'Hetero-Epitaxie et ses Applications)


Breakthroughs in the growth and doping of GaN materials in the 1990s led to the discovery of the elusive blue light-emitting diode (LED), which rapidly evolved into solid-state lighting products that became widely adopted within 20 years of its invention. The III-V material and its alloys are not only suitable for manufacturing LEDs but is also ideal for the development of visible/ultraviolet laser diodes which are in huge demand for applications including printing, spectroscopy and projection displays.

The violet light laser diodes widely used today are predominantly of the edge-emitting type, which are larger in dimensions and cannot be arrayed. Although vertical-cavity surface-emitting lasers (VCSELs) can be made compact in size and be processed at the wafer level, the introduction of grown distributed Bragg reflector (DBR) stacks compromises on their feasibilities and performances. The whispering-gallery mode (WGM) microdisk lasers overcome these limitations, and can potentially take solid-state lighting to unprecedented levels of efficiencies.

Light-emitting diodes (LEDs) suffer from efficiency droop, a phenomenon of reduced efficiency at higher operating current densities. Laser diodes operate inherently at higher current densities which overcomes the droop issue and with narrow spectral linewidths for efficient excitation of phosphors. Lighting based on edge laser bars has been since been proposed and demonstrated. However the high power beam from a single laser bar is hardly suitable for large-area lighting; an array of laterally-emitting WG lasers is well-suited for this application. Light emitted from the edges of microdisks excite the phosphors deposited between the microdisks, generating broadband light that is scattered in all directions for homogenous white light emission.

The GaN-on-Si platform offers optical opaqueness for confinement and electrical conductivity, but has traditionally not been favored due to lattice and thermal mismatch. The team at CNRS-CRHEA has overcome these problems by introducing microstructures on the Si substrates, leading to significant reductions to defect densities and thus high-quality multi-quantum wells. The GaN group at HKU has developed the “pivoted GaN-on-Si microdisk” which enables optimal optical isolation of the optical microcavity from its substrate for maximal optical confinement. These two technologies have been successfully combined to form thin microdisks lasers, with recent demonstration of optical pumped. The main target of this project is to enable electrical-injection to the microdisk lasers. Combining the material epitaxy expertise of the French group with the strengths of optical design and micro/nano-fabrication at the HKU group, this challenge will be conquered.

A-HKUST603/17
Neurotransmitter release and receptor diffusion dynamics during inhibitory synaptic transmission

Hong Kong Principal Investigator: Prof Park Hyokeun (The Hong Kong University of Science and Technology)
French Principal Investigator: Prof Antoine Triller (École Normale Supérieure)

Transfer of information between neurons requires the precise alignment between releasing sites of neurotransmitters in presynaptic terminals and locations of activating receptors in postsynaptic terminals. Recently, super-resolution microscopy has allowed defining the so-called “nano-column” at excitatory synapses, which is a substructure allowing the close apposition of presynaptic release sites and postsynaptic receptors in tiny areas. Although inhibitory synapses regulate excitability in networks accurately, the functional alignment between releasing sites of inhibitory synaptic vesicles and inhibitory receptors has not been studied yet. One reason lies in the difficulty in real-time imaging individual vesicles and receptors whose sizes are smaller than the optical resolution of classical fluorescence microscopes. Our objective is to investigate simultaneously the release of vesicles and the diffusion dynamics of apposing receptors in inhibitory synapses and understand their precise alignment and dynamics.

The proposed project is made possible by recent progress in the single-molecule fluorescence technique. More precisely: 1) Prof. Hyokeun Park at HKUST in Hong Kong has built a state-of-the-art real-time three-dimensional nanometer-accuracy tracking microscopy setup, which enables to track individual synaptic vesicles (40 nm in diameter) with higher accuracy than its diameter; 2) Prof. Antoine Triller at École Normale Supérieure (ENS) in Paris has successfully tracked individual postsynaptic receptors in live neurons for the first time and found dynamics of receptors in postsynaptic compartments. He has recently developed single-particle tracking with 20 nm accuracy using super-resolution PALM microscopy and showed the activity-dependent stabilization of postsynaptic receptors by scaffolding proteins. Our team possesses a unique combination of skills important for this project. We will study specific properties of GABAergic and glycinergic nano-columns in cultured striatal and spinal cord neurons, respectively. To achieve this aim, we will first develop microscopy and molecular tools to observe simultaneously the release of neurotransmitters and the diffusion behavior of receptors. We will investigate how neuronal activities control exocytosis and the diffusion of receptors. This will lead us to propose frameworks for the molecular control of a functional nano-column at inhibitory synapses. Ultimately, we will model the consequences of these coordinated pre-and post-synaptic activities for dynamic equilibrium ensuring the stability and short-term plasticity of synapses.

This research will provide a functional counterpart to the inhibitory nano-column for the first time by observing simultaneously the release of neurotransmitters and the mobility of receptors. Furthermore, this research will provide a new framework from pharmacology at synapses and pathogenic mechanisms for neurological disorders caused by defects in inhibitory synaptic transmission.