項目名稱：植物與環境互作基因組研究中心：可持續農業與糧食安全
項目統籌人：林漢明教授（中大）

摘要
以國際卓越為目標發展創新性農業。水資源短缺、全球變暖以及表層土枯竭是阻礙農業可持續發展和糧食安全的主要因素。為應對這些重大問題, 我們建立了一支在植物基因組學及分子生物學方面具備卓越科研實力的團隊，利用多學科的手段探究植物和農業科學中的一個根本問題──植物與環境的互作。我們研究的焦點是了解植物如何適應非生物脅迫，以及植物與微生物之間的相互作用。基於大豆在可持續農業中的重要性，以及我們在大豆基因組學研究中已取得的重要成果，包括完備的大豆基因組序列數據庫、獨特的種質資源和遺傳群體等，我們選擇了以大豆作為我們的主要模式作物。目標是通過這研究計劃來開發新的知識和技術，從而闡明植物與環境相互作用的基本機制並應用到其他作物。

啟動全球性可持續農業研究。我們的目標是建立一個穩定而且具有精確基因組注釋的大豆遺傳群體及其在線數據庫平台，從而對國際可持續農業產生長遠的影響。我們將研究大豆根部在非生物脅迫下，與生長相關的遺傳及氧化還原調節機制，並深入分析當植物處於非生物脅迫時，基因表達的再程序化。而重點將集中在基因組研究的兩個嶄新機制上──染色質變化和非編碼 RNA。由於根瘤是豆科植物中的一種獨特組織，我們將研究與根瘤中線粒體功能相關的能量流動，基因表達和 RNA 編輯。同時，我們亦會研究大豆的種植系統如何影響根瘤菌在土壤中的進化。此項研究的最終目的是鑒定出有用的功能基因及高效的 DNA 標記。我們會利用這些資訊通過轉基因或標記輔助育種來開發具備高新適應能力的大豆品種。

建立尖端技術作下游應用。團隊的預期成果為：（1）在高質量科研雜誌上發表重要的科學發現；（2）提供一個基因組數據庫平台供研究人員和育種人員使用；（3）開發能適應環境挑戰的新品種；（4）培養高素質的博士後研究員和研究生，成為未來植物基因組學和分子生物學方面的專家；以及（5）建立一個國際性的作物科學研究網絡。

項目名稱： 健康及神經退行性病變過程中突觸功能和可塑性調控的細胞機制
項目統籌人： 葉玉如教授（科大）

摘要
神經元突觸是控制腦功能的關鍵部位。突觸的強度具有可調節的特性，我們稱之為突觸可塑性。這種突觸可塑性對於連接和維持神經網絡至為重要，也是學習和記憶的基礎機制。突觸的缺失及功能障礙與阿爾茨海默氏病（AD）等神經退化性疾病有關，進一步突顯其重要性。突觸可塑性受不同的生物化學途徑嚴密調控。這些途徑是通過突觸前和突觸後的神經元之間的雙向信號傳導，也受神經元和星形膠質細胞、小膠質細胞等神經膠質細胞之間的通信所影響，但具體過程不詳。若能破解其中機制，就能明白神經迴路中的資訊傳遞過程，以及學習和記憶中突觸可塑性的調控途徑。

為了揭開突觸可塑性的機制，我們將會針對神經元之間，以及神經元和神經膠質細胞之間的精確信號傳導和細胞生物學機制進行深入研究。這些細胞通信對突觸功能和網絡連接、以及學習和記憶過程有調控作用。具體而言，我們將會追蹤在神經迴路中各種受體配體的細胞來源，以及這些信號傳導途徑在腦部的解剖學分佈，之後會研究它們對突觸功能和可塑性、神經迴路活性以及學習和記憶的影響。一旦確定了這些重要調節機制的生理作用，我們就會探討機制失調與神經退行性疾病，尤其是與AD病理生理學之間的關係。恢復突觸的數量和功能，可能會為治療AD提供新的策略。本項目的成果將會促進生物標誌物和突觸修復策略的研發，有利於預防或延緩AD患者的認知功能障礙。

本項目將為解析學習和記憶的機制提供重要基礎，並會揭示在AD等神經退行性疾病中，與認知功能障礙有關的重要信號途徑和分子。項目成果將會促進新療法的開發，應付這些目前尚未能治癒的疾病，從而改善全世界數以百萬計患者的生活。本項目亦會提升香港作為神經科學卓越中心的聲譽，突顯香港優秀的科研能力、基礎設施和高端人才。

項目名稱：以化學生物學方法探索分子醫學
項目統籌人：楊丹教授（港大）

摘要
化學生物學結合合成化學、化學分析和生物技術的優勢,以求在分子水準上深入探究和精準調控生物體系。區別於傳統的生物化學研究，化學生物學家設計、開發並應用新穎的分子工具來研究生物系統。化學生物學的關鍵研究領域包括：分子設計與合成、分子探針、化學遺傳學、化學蛋白質組學、分子模擬和結構生物學。在過去的十年間，化學生物學的快速發展，不僅為科學界提供了許多寶貴的研究工具以闡明關鍵生物機制，而且極大地促進了疾病診斷與治療方法的發展。作為高速發展的化學前沿領域，化學生物學是驅動分子醫藥、精準治療和先進生物技術取得創新突破的新動力。近年來，世界頂級學府包括哈佛大學，麻省理工學院，史丹福大學和芝加哥大學紛紛投入大量資源以建立化學生物學研究中心；加州大學柏克萊分校和哈佛大學亦在本科生教育中加入化學生物學課程以培養專長人才。這些變化都突顯了化學生物學研究具有重要的社會經濟意義。

香港擁有優越的科學專長，特別是在化學和生物醫學研究方面更具優勢，因此香港理應通過加強化學生物學的基礎研究來引領本地生物科技產業的創新和發展。近年來，香港所有大學都聘用了以化學生物學為研究重點的教員，他們一直活躍於化學生物學的研究前沿，並在一些研究領域達到國際領先水平。在本項目團隊中，來自香港三所主要大學的研究人員將運用化學生物學的研究方法，共同努力解決分子醫學的挑戰性問題。具體來說，我們計劃打造一流的化學生物學研究平台，在分子水平上深入研究重要的生命過程和生物機制（例如蛋白質翻譯後修飾和氧化應激），並致力於開發新的人類疾病治療和診斷方法。本項目的實施將大大提升香港在化學生物學領域的研究水平，促進多學科、跨機構合作研究，並推動解決分子醫學領域若干重要問題，為保持香港科學研究的競爭優勢並發展成一個世界上著名的化學生物學研究中心提供堅實的支撐。

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.