Areas of Excellence Scheme - Seventh Round Layman Summaries of Projects Funded

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

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)

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)

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.