项目名称：植物与环境互作基因组研究中心：可持续农业与粮食安全
项目统筹人：林汉明教授（中大）

摘要
以国际卓越为目标发展创新性农业。水资源短缺、全球变暖以及表层土枯竭是阻碍农业可持续发展和粮食安全的主要因素。为应对这些重大问题, 我们建立了一支在植物基因组学及分子生物学方面具备卓越科研实力的团队，利用多学科的手段探究植物和农业科学中的一个根本问题──植物与环境的互作。我们研究的焦点是了解植物如何适应非生物胁迫，以及植物与微生物之间的相互作用。基于大豆在可持续农业中的重要性，以及我们在大豆基因组学研究中已取得的重要成果，包括完备的大豆基因组序列数据库、独特的种质资源和遗传群体等，我们选择了以大豆作为我们的主要模式作物。目标是通过这研究计划来开发新的知识和技术，从而阐明植物与环境相互作用的基本机制并应用到其他作物。

启动全球性可持续农业研究。我们的目标是建立一个稳定而且具有精确基因组注释的大豆遗传群体及其在线数据库平台，从而对国际可持续农业产生长远的影响。我们将研究大豆根部在非生物胁迫下，与生长相关的遗传及氧化还原调节机制，并深入分析当植物处于非生物胁迫时，基因表达的再程序化。而重点将集中在基因组研究的两个崭新机制上──染色质变化和非编码 RNA。由于根瘤是豆科植物中的一种独特组织，我们将研究与根瘤中线粒体功能相关的能量流动，基因表达和 RNA 编辑。同时，我们亦会研究大豆的种植系统如何影响根瘤菌在土壤中的进化。此项研究的最终目的是鉴定出有用的功能基因及高效的 DNA 标记。我们会利用这些信息通过转基因或标记辅助育种来开发具备高新适应能力的大豆品种。

建立尖端技术作下游应用。团队的预期成果为：（1）在高质量科研杂志上发表重要的科学发现；（2）提供一个基因组数据库平台供研究人员和育种人员使用；（3）开发能适应环境挑战的新品种；（4）培养高素质的博士后研究员和研究生，成为未来植物基因组学和分子生物学方面的专家；以及（5）建立一个国际性的作物科学研究网络。

项目名称： 健康及神经退行性病变过程中突触功能和可塑性调控的细胞机制
项目统筹人： 叶玉如教授（科大）

摘要
神经元突触是控制脑功能的关键部位。突触的强度具有可调节的特性，我们称之为突触可塑性。这种突触可塑性对于连接和维持神经网络至为重要，也是学习和记忆的基础机制。突触的缺失及功能障碍与阿尔茨海默氏病（AD）等神经退化性疾病有关，进一步突显其重要性。突触可塑性受不同的生物化学途径严密调控。这些途径是通过突触前和突触后的神经元之间的双向信号传导，也受神经元和星形胶质细胞、小胶质细胞等神经胶质细胞之间的通信所影响，但具体过程不详。若能破解其中机制，就能明白神经回路中的信息传递过程，以及学习和记忆中突触可塑性的调控途径。

为了揭开突触可塑性的机制，我们将会针对神经元之间，以及神经元和神经胶质细胞之间的精确信号传导和细胞生物学机制进行深入研究。这些细胞通信对突触功能和网络连接、以及学习和记忆过程有调控作用。具体而言，我们将会追踪在神经回路中各种受体配体的细胞来源，以及这些信号传导途径在脑部的解剖学分布，之后会研究它们对突触功能和可塑性、神经回路活性以及学习和记忆的影响。一旦确定了这些重要调节机制的生理作用，我们就会探讨机制失调与神经退行性疾病，尤其是与AD病理生理学之间的关系。恢复突触的数量和功能，可能会为治疗AD提供新的策略。本项目的成果将会促进生物标志物和突触修复策略的研发，有利于预防或延缓AD患者的认知功能障碍。

本项目将为解析学习和记忆的机制提供重要基础，并会揭示在AD等神经退行性疾病中，与认知功能障碍有关的重要信号途径和分子。项目成果将会促进新疗法的开发，应付这些目前尚未能治愈的疾病，从而改善全世界数以百万计患者的生活。本项目亦会提升香港作为神经科学卓越中心的声誉，突显香港优秀的科研能力、基础设施和高端人才。

项目名称：以化学生物学方法探索分子医学
项目统筹人：杨丹教授（港大）

摘要
化学生物学结合合成化学、化学分析和生物技术的优势,以求在分子水准上深入探究和精准调控生物体系。区别于传统的生物化学研究，化学生物学家设计、开发并应用新颖的分子工具来研究生物系统。化学生物学的关键研究领域包括：分子设计与合成、分子探针、化学遗传学、化学蛋白质组学、分子模拟和结构生物学。在过去的十年间，化学生物学的快速发展，不仅为科学界提供了许多宝贵的研究工具以阐明关键生物机制，而且极大地促进了疾病诊断与治疗方法的发展。作为高速发展的化学前沿领域，化学生物学是驱动分子医药、精准治疗和先进生物技术取得创新突破的新动力。近年来，世界顶级学府包括哈佛大学，麻省理工学院，史丹福大学和芝加哥大学纷纷投入大量资源以建立化学生物学研究中心；加州大学柏克莱分校和哈佛大学亦在本科生教育中加入化学生物学课程以培养专长人才。这些变化都突显了化学生物学研究具有重要的社会经济意义。

香港拥有优越的科学专长，特别是在化学和生物医学研究方面更具优势，因此香港理应通过加强化学生物学的基础研究来引领本地生物科技产业的创新和发展。近年来，香港所有大学都聘用了以化学生物学为研究重点的教员，他们一直活跃于化学生物学的研究前沿，并在一些研究领域达到国际领先水平。在本项目团队中，来自香港三所主要大学的研究人员将运用化学生物学的研究方法，共同努力解决分子医学的挑战性问题。具体来说，我们计划打造一流的化学生物学研究平台，在分子水平上深入研究重要的生命过程和生物机制（例如蛋白质翻译后修饰和氧化应激），并致力于开发新的人类疾病治疗和诊断方法。本项目的实施将大大提升香港在化学生物学领域的研究水平，促进多学科、跨机构合作研究，并推动解决分子医学领域若干重要问题，为保持香港科学研究的竞争优势并发展成一个世界上著名的化学生物学研究中心提供坚实的支撑。

Project Title: Center for Genomic Studies on Plant-Environment Interaction for Sustainable Agriculture and Food Security
Project Coordinator: Prof Hon-ming Lam (CUHK)

Abstract
To pursue international excellence on innovative agriculture. Water scarcity, global warming and topsoil depletion are among the major factors hampering sustainable agriculture and food security. Here we have a strong team excelling in both plant genomics and molecular biology, using a multidisciplinary approach to address a very fundamental question in plant and agricultural sciences: how do plants interact with their environment? The focus of our research is to understand how plants adapt to abiotic stresses and how plants interact with microbes. We choose soybean as our primary crop model due to its importance in sustainable agriculture, our previous successes in soybean genomic studies, the availability of our soybean genomic sequence database, unique germplasms and genetic populations. New knowledge and technologies acquired through the proposed research can then be applied to other crops in delineating the underlying mechanisms of plant-environment interactions.

Endeavoring for sustainable agricultural research with high global impact. Aiming for long-lasting international impact, we will establish a stable soybean genetic population with precise annotated genomic information and online platform. We will study the genetic as well as redox regulation in relation to root growth under abiotic stress. We will thoroughly analyze the gene expression re-programming when plants are under abiotic stresses, with emphases on two new mechanisms that are at the forefront of current genomic researches: chromatin changes and non-coding RNAs. Since root nodule is a unique organ in legume plants that directly interacts with the soil, we will investigate the energy fluxes, gene expressions and RNA editing related to the functions of mitochondria in root nodules. Bilaterally, we will also study how several prevalent soybean cultivation systems impact the evolution of rhizobia in soil. The ultimate goals are to identify useful functional genes and effective DNA markers. We will make use of this information to generate prototypes of new adaptive soybean varieties by either transgenesis or marker-assisted breeding.

Develop cutting-edge technology with downstream applications. We pledge to deliver: (1) high-quality publications reporting important scientific findings; (2) a platform to disseminate genomic information to researchers and breeders; (3) prototypes of new varieties that are more adaptive to environmental challenges; (4) high-caliber trained personnel at the level of postdoctoral associates and graduate students who will be experts in the field of plant genomics and molecular biology; and (5) an international research network on crop sciences.

Project Title: Cellular mechanisms of synaptic functions and plasticity in health and neurodegenerative diseases
Project Coordinator: Prof Nancy Ip (HKUST)

Abstract
Neuronal synapses are critical for brain function. Modulation of their strength, termed synaptic plasticity, is essential for connecting and maintaining the neural network, and is the fundamental mechanism underlying learning and memory. Loss of synapses and their dysfunction are linked to neurodegenerative diseases such as Alzheimer's disease (AD), further highlighting their importance. Synaptic plasticity is tightly regulated and modulated by various biochemical pathways, which are mediated by bidirectional signaling between pre- and postsynaptic neurons as well as communication between neurons and glial cells such as astrocytes and microglia. However, these processes are poorly understood. Thus, deciphering these specific mechanisms holds the key to understanding the regulatory pathways that mediate information flow in the neural circuit and govern synaptic plasticity in learning and memory.

To unravel the mechanisms underlying synaptic plasticity, we will examine the precise signaling and cellular mechanisms governing neuron-neuron and glial-neuron communication, which modulate synaptic functions and network connectivity as well as learning and memory. In particular, the cell population source of the receptor ligands within the neural circuit and the anatomical organization of these signaling pathways in the brain will be examined, and their effects on synaptic function and plasticity, neural circuit activity, and learning and memory will subsequently be investigated. Once we have determined the physiological roles of these key regulatory mechanisms, we will investigate how their deregulation contributes to the pathogenesis of neurodegenerative diseases, with a specific focus on AD. Restoring synaptic loss and function is a promising strategy for treating AD, and new insights and findings from the project will accelerate the development of biomarkers and synaptic repair strategies to prevent or delay cognitive dysfunctions in AD.

This project will lay crucial groundwork for delineating the mechanisms underlying learning and memory, and implicating key pathways and molecular players involved in cognitive dysfunction in neurodegenerative diseases such as AD. Successful completion of the project will greatly facilitate development of new therapies to tackle these incurable diseases, thereby improving the lives of millions of afflicted patients worldwide. The project will also enhance Hong Kong's growing reputation as a center of excellence for neuroscience and will highlight the territory's excellent scientific research capabilities, infrastructure, and highly skilled work force.

Project Title: Chemical Biology Approach to Molecular Medicine
Project Coordinator: Prof Dan Yang (HKU)

Abstract
Chemical biology combines the power of synthetic chemistry, chemical analysis, and biological techniques to understand and manipulate biological systems with molecular precision. In contrast to biochemists who study the chemistry of biomolecules and regulation of biochemical pathways, chemical biologists apply novel chemical compounds to probe biological systems. Molecular design and synthesis, molecular probes, chemical genetics, chemical proteomics, molecular modelling and structural biology are the key components of chemical biology. In the past decade, the rapid development of chemical biology has not only provided numerous valuable research tools to elucidate fundamental biological mechanisms, but also prompted the discovery of important therapeutic agents to treat human diseases. Chemical biology has emerged as a fast-growing and exciting frontier of chemistry and is expected to be a new driving force for important future advances in molecular medicine and biotechnology. The socioeconomic significance of chemical biology research has been highlighted by the vast amounts of resources invested by top US universities such as Harvard, MIT, Stanford, and Chicago to build up centres of chemical biology research as well as the introduction of chemical biology curriculum in undergraduate education in UC Berkeley and Harvard.

Hong Kong is ideally positioned to lead innovation in biotechnology through fundamental chemical biology research because of its excellent scientific expertise, especially in the chemistry and biomedical research. All universities in Hong Kong have recruited faculty members with chemical biology focus, many of them have been very active in frontier chemical biology research and achieved international pre-eminence. In this AoE proposal, PIs from three major universities of Hong Kong will join efforts to tackle challenging problems of molecular medicine via a chemical biology approach. Specifically, we plan to build up chemical biology research platforms, to understand fundamental biological processes (such as post-translational modification and oxidative stress) at molecular level, and to develop novel therapeutic approach to human diseases. The proposed AoE in chemical biology will significantly strengthen our current research efforts and collaborations, solve important problems of molecular medicine, maintain the competitive edge of Hong Kong, and build up a leading chemical biology program in the world.