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Areas of Excellence Scheme - 6th Round

Discipline: Biology and Medicine
Project Title: Centre for Organelle Biogenesis and Function
Project Coordinator: Professor Liwen Jiang (CUHK)

The existence of all eukaryotic cells, plant and animal, depends upon the maintenance of organelles within them. Organelles are membrane-bound compartments that contain specialized environments where crucial complex biochemical processes occur. Organelles are essential for cell-cell communications and for an organism's homeostasis, growth and development as well as for responses to the environment. However, the underlying mechanisms of organelle biogenesis and protein traffic communications among them remain elusive. Over the past ten years, our research programs in Hong Kong have made internationally recognized contributions towards understanding protein trafficking, organelle dynamics and functions in model organisms including plants, yeast and mice. For example, in plant cells, we first identified the multivesicular body (MVB) as a prevacuolar compartment (PVC), defined the trans-Golgi network (TGN) as an early endosome, and discovered a novel organelle termed EXPO (Exocyst-positive Organelle) mediating an unconventional protein secretion (UPS). Similarly, we identified novel Golgi-retention mechanisms for glycosyltransferases (GTases) in yeast and Arabidopsis EMPs (endomembrane proteins), and elucidated the roles of PICK1 (Protein Interacting with C-Kinase 1) in AMPA receptor trafficking and synaptic plasticity in mice brains. This documented scientific expertise and leadership in multiple disciplines provides the opportunity and rationale for forming a team to establish the Centre for Organelle Biogenesis and Function that will bring together team members with excellent track records to focus on a broad theme of organelle biogenesis and function, using a combination of cellular, molecular, biochemical, physiological, genetic and omics approaches in model organisms. The present proposal focuses on understanding the Biogenesis and Function of three organelles: Golgi, TGN and EXPO. Our research will not only address the fundamental questions concerning organelle biogenesis and function in important biological processes, such as cell wall formation and stress signaling pathways in plants, but will also have potential applications for the biotechnology industry in Hong Kong and China to improve the value of plants as biofuel feedstocks and to enhance crop productivity in high-stress environments.

Discipline: Biology and Medicine
Project Title: Mechanistic Basis of Synaptic Development, Signalling and Neuro-disorders
Project Coordinator: Professor Mingjie Zhang (HKUST)

Mental illness is the leading burden to the world among all chronic human diseases, and yet very few effective treatments are available. For better treatments, better science is needed. However, the human society is facing a huge crisis as drug companies-major investors of mental illness research in the past-are withdrawing from mental illness research due to the slow commercial returns of their investments as well as complicated mechanistic bases of the diseases. Accordingly, academia is thus challenged with the tasks of conducting both deeper and broader research activities in the field. But it also opens up many opportunities that are otherwise the territories of the pharmaceutical industry. Additionally, advancements in technologies such as high throughput genomic sequencing and in systems biology have generated and will continue to generate (at an even faster pace) a very large number of candidate genes that are associated with various human brain disorders. Totally unmatched to the discoveries of hundreds of disease-causing genes, the underlying biology of why alterations of these genes is very poorly understood. Thus, elucidating the action mechanisms of these genes will be one of the most important research directions in many years to come for understanding mental disorders as well as for developing treatments methods for these diseases.

In this proposed AoE project, we plan to investigate the physiological roles and action mechanisms of a set of key proteins and their complexes that are known to play fundamental roles in development and signalling of synapses in excitatory neurons. We are also particularly interested in the underlying mechanisms of human mental illnesses (such as autism, schizophrenia, depression, etc., broadly defined as neuro-disorders in this proposal) caused by the malfunctioning of the proteins that orchestrate neuronal development and synaptic signalling, and in suggesting/developing possible therapeutic approaches for these diseases. This team will address these topics through a combination of genetic, cellular, biochemistry, structural biology and chemical biology approaches. Unlike numerous other groups/consortiums in neuronal signaling and neuro-disorder research worldwide, our research program will consist of structural biology and biochemistry-based mechanistic studies at its core. These mechanistic-based studies will be supported by, and in turn drive, "upstream" functional studies that use animal model and cellular approaches on the one hand, and will function as the basis for developing peptides, peptide mimetics, and low molecular weight compounds with therapeutic potentials using chemical biology approaches on the other hand.

This proposed project is built on our 15+ years of systematic and collaborative research experience in neuronal development and signalling. We have assembled a highly competitive team with members who are leading experts in their respective areas and who have demonstrated excellent collaboration records in the past. We are poised to make important contributions to the understanding of normal brain functions and to the fight against mental illnesses resulting from synaptic functional defects. The project will also enhance Hong Kong's excellent scientific research capabilities, infrastructure, and work force, and establish a top-notch research center for neural development, signaling and neuro-disorders in the territory.

Discipline: Physical Sciences
Project Title: Novel Wave Functional Materials for Manipulating Light and Sound
Project Coordinator: Professor Che-ting Chan (HKUST)

The ubiquitous presence of electromagnetic and acoustic waves means that their study dates back to the antiquities. Their diverse applications form the very pillars of our modern existence. About two decades ago, the incipient stage of a revolution began in this classic field, propelled by both theory and experiments, which demonstrate the feasibility of realizing man-made materials with wave manipulation functionalities beyond the defined limits of those found in nature. These "wave functional materials" include photonic/phononic crystals, metamaterials and plasmonic structures. The purpose of this AoE proposed project, based on the existing strengths of Hong Kong researchers and their early and pioneering participation in this rapidly evolving area, is to lift our collective level one notch higher, with an eye towards potential applications that can support and define the next generation of wave-related devices.

The simplest example of a wave functional material is a lens that constitutes the key component of microscopes and telescopes. Ordinary lenses are made of a single material, glass, with crafted surfaces. By employing multi-component composites in conjunction with advances in theory and fabrication technology, new degrees of freedom in controlling waves have now become available. The new materials thus fabricated can be optimized for a specific functionality. If the constituent units and the lattice period are smaller than the wavelength, the material is called a "metamaterial;" if they are close to a wavelength, the material is called a "photonic crystal;" and if the units are made of nano-scale structures resonant at optical frequencies, the material is called a "plasmonic structure." These novel materials can manipulate waves to create science-fiction type effects such as invisibility and stealth and can control elastic waves so as to make mass appear negative in certain frequency regimes and can be used to make "superlens" that are free of aberration, just to name a few unconventional phenomena not achievable before.

Researchers in Hong Kong have been at the forefront of this exciting scientific development right from the beginning. Our team members have introduced fundamentally new concepts such as photonic quasi-crystals, negative dynamic mass, acoustic metamaterials, remote cloaking, illusion optics and optical pulling force. With this AoE, we intend to collectively stay at the leading edge of this very rapidly advancing scientific front and to reap timely benefits for Hong Kong, such as prototype developments that can eventually be relevant to future technologies.