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NSFC/RGC Joint Research Scheme 2018/19 Supported Applications - Layman Summaries of Projects Funded in 2018/19 Exercise

Bioinspired Molecular Systems for Catalytic CO2 Reduction Based on Earth-abundant Metal Complexes

Hong Kong Principal Investigator: Prof Lau Tai-chu (City University of Hong Kong)
Mainland Principal Investigator: Prof Zhang Jun-long (Peking University)

The purpose of this project is to develop efficient photo- and electro-catalysts for the reduction of carbon dioxide based on earth abundant transition metal complexes. Since our fossil fuels are being used up rapidly, it is estimated that we need an additional 14-20 TW per year by 2050. One of the most promising sources of carbon neutral and renewable energy comes from the reduction of CO2 to generate various fuels, including CO, methanol or light hydrocarbons. Since CO2 is a stable molecule, the design of efficient catalysts is necessary in order for its reduction to occur at reasonable rates with low over-potentials. Ideally, the energy required for CO2 reduction should be obtained from solar energy, since more solar energy strikes the earth in one hour than can be consumed by the whole planet in one year. In this project, we propose to design highly active and robust homogeneous CO2 reduction catalysts based on molecular transition metal complexes. In order to be economically viable, the complexes should be made from earth-abundant metals, such as Mn, Fe, Co, Ni and Cu. So far, few catalysts constructed from these metals are active and robust enough to be of practical use.

Molecular catalysts are our starting point in this project because their structures are more well- defined and in general they have higher catalytic activity than solid material catalysts. Their reactivity and redox properties can be readily tuned by systematic variation of the ligands. However, solid material catalysts are in general more robust than molecular catalysts. Hence, in this project selected catalysts will be anchored onto various solid supports and electrode surfaces to increase their stability, ease of product separation and catalyst recycling. Ru-based and Ir-Based photosensitizers such as [Ru(bpy)3]2+ and [Ir(ppy)3] are commonly used for photocatalytic CO2 reduction, however these photosensitizers are based on precious metals.

Hence, we will also design robust and cheap photosensitizers in this project. We will also carry out computational studies to provide insights into the mechanisms of CO2 reduction, which would provide feedback to the design of better catalysts. This project should contribute to the development of a new class of practical catalysts for the reduction of carbon dioxide.

Synthesis of New Carborane-Based Ligands and Their Applications in Rare-Earth Metal Chemistry

Hong Kong Principal Investigator: Prof Quan Yangjian (The Chinese University of Hong Kong)
Mainland Principal Investigator: Prof Wang Shaowu (Anhui Normal University)

Organo-rare-earth metal complexes are finding valuable applications in organic synthesis, polymerization and optical/magnetic materials, which has drawn a considerable attention to rare-earth chemistry and materials science. Among all the factors, ligands impose a dominant control over both the chemical and physical properties of the corresponding organo-rare-earth metal complexes. Therefore, ligand design has become a central theme in the coordination chemistry of rare-earth metals. To promote the progression of rare-earth chemistry, the design and development of new multifaceted ligands is eagerly desired.

Carboranes, a class of icosahedral carbon-boron molecular clusters, are often viewed as three-dimensional analogues to 2D benzene. Their unique icosahedral geometry and three-dimensional aromaticity by σ-bond conjugation render them as intriguing 3D ligands for transition metals, which have been found to bind with metals in diversiform modes including 1ղ, 2ղ, 5ղ, 6ղ, and 7ղ fashion. The Xie’s group has pioneered the development of carborane-based ligands, preparing a series of carborane-cyclopentadiene combinations that leads to a new class of organometallic compounds with new properties and applications (Acc. Chem. Res. 2003, 36, 1). Considering the advantages of carborane moiety and recent progress of employing indole and carbene as valuable ligands, we propose to synthesize a brand new class of linked carborane-indole and carborane-carbene (carborane-silylene and carborane-germylene) compounds for applications in rare-earth metal chemistry. The main goal of the joint proposal is to bring together the expertise of both Hong Kong and mainland teams to build a library of this new type of organic-inorganic/electronic rich-deficient hybrid ligands which would be extremely useful for the production of rare-earth metal complexes for further investigation of their reactivity and catalytic performance.

Molecular Tunnel Junctions for Control of Localized and Propagating Plasmons

Hong Kong Principal Investigator: Prof Shao Lei (The Chinese University of Hong Kong)
Mainland Principal Investigator: Prof Zhang Wei (Institute of Applied Physics and Computational Mathematics)

The aim of this proposal is to further our understanding of quantum plasmons in molecular-tunnel-junctions-bridged nanocavities, extend our capabilities to control these plasmons and put them into practical applications.

Metallic nanostructures can couple efficiently to light because of their plasmon resonances, which are collective, coherent oscillations of their conduction electrons. When two metallic structures are close to each other, their plasmon resonances are coupled, resulting in frequency shifts of plasmon resonances and significant enhancements of local electromagnetic fields in the formed plasmonic gap. The coupled plasmonic nanostructures therefore have many important applications, among which the most mature one is probably surface-enhanced spectroscopies. For example, the plasmonic gap can enhance the Raman scattering signal of molecules in the gap dramatically, enabling the detection of Raman scattering from an individual molecule.

Classical electromagnetic theory predicts that the plasmon resonance frequency shift and the local field enhancement increase monotonically with decreasing gap width. This prediction breaks down as the gap decreases to a few angstroms. The tunneling current in the plasmonic nanocavity driven by the large fields becomes significant, leading to decreased coupling strength and local field enhancement. The electrons can transfer back and forth across the gap and a charge-transfer plasmon emerges. The tunneling plasmonics brings intriguing applications such as nanoscale optoelectronics and ultracompact optical circuits. However, it is challenging to fabricate nanocavities with such narrow gaps in a reliable and repeatable manner by current state-of-the-art technology. Alternatively, one can bridge the cavities with conductive molecular junctions, which provide a tunneling channel at moderate gap distances and allow for the observation of quantum effects of plasmons at an over-one-nanometer gap. Up to now, the study of quantum plasmon in molecular-tunnel-junctions-bridged nanocavities is still in its early stage and many unanswered questions remain.

Here, we propose to develop large-scale fabrication of molecular-tunnel-junctions-bridged nanocavities from metal nanocrystals and use them as a platform for quantum plasmonics study. We will perform optical/electrical measurements and theoretical modelling to investigate how different molecular junctions modulate the tunneling charge transfer at optical frequencies and therefore control both the localized and propagating plasmons. We will further explore the modulation of such quantum plasmonic structures and their application for hot carrier excitation and photodetection.

We foresee that the success of this project will deepen our understanding on quantum plasmons in molecular-plasmonic structures. Our study will also boost the research towards molecular plasmonic devices and ultrafast on-chip integrated plasmonic electronic circuits.

Study on the Mechanism Underlying BMAL1/CLOCK-mediated Regulation of Human Stem Cell Homeostasis and Aging

Hong Kong Principal Investigator: Prof Sun Hao (The Chinese University of Hong Kong)
Mainland Principal Investigator: Prof Liu Guanghui (The Institute of Biophysics, Chinese Academy of Sciences)

Understanding the cause of aging is an area of keen interest throughout human history. The decline in adult stem cell function has been thought to be one of the drivers of aging thus it is imperative to elucidate the underlying molecular mechanisms. Here in this study we propose to investigate the functional roles of circadian clock in regulating stem cell homeostasis and aging. Humans show a decline in the robustness of Circadian clock controlled circadian rhythmicity during aging. BMAL1 and CLOCK are core circadian genes that control circadian rhythmicity. Deletion of Bmal1 and Clock in mice results in aging-like pathologies, suggesting their key roles in aging. However, the exact roles of how BMAL1 and CLOCK regulate the aging process for example the stem cells homeostasis remain unknown. In this proposal, we aim to fill the gaps by generating BMAL1-null and CL0CK-null human embryonic stem cells (hESCs) as well as the KO mouse models using CRISPR/Cas9 mediated gene editing technique. The effects of BMAL1 and CLOCK loss on the pluripotency and differentiation of hESCs towards mesenchymal stem cells, neural stem cells, myotube cells, vascular endothelial cells will be examined; Furthermore, the impact of their loss on homeostasis and aging of adult stem cell will be evaluated in vivo on the mice. Lastly, the association of BMAL1 and CLOCK in human aging will be confirmed using the established aging model in our group. Altogether, findings from the proposed study will lead to a better understanding of the molecular mechanism underlying BMAL1/CLOCK functions in regulating human stem cell homeostasis and aging.

Hybrid Antimicrobial Peptide-Nylon-3 Polymers to Treat Infection in the Brain

Hong Kong Principal Investigator: Prof Xia Jiang (The Chinese University of Hong Kong)
Mainland Principal Investigator: Prof Liu Runhui (East China University of Science and Technology)

Microbial infection is a global problem, as more and more cases of resistance to current antibiotic therapeutics recently emerge. The globalization process makes the surveillance and confinement of the infected cases a big challenge, particularly in an international city like Hong Kong. Microbial infection in the brain is even more difficult to treat as most therapeutics cannot cross the blood-brain barrier (BBB). While the field is seeking antibiotics that can cross BBB effectively, macromolecular antimicrobial agents are also promising candidates. Peptides have been shown to be part of the natural defensing system that organisms at all levels use to combat the invading pathogens. Yet the biggest challenge is to deliver the antimicrobial peptides through the BBB and to distribute into the infected site in the brain.

Both labs in mainland China and Hong Kong are very experienced with developing antimicrobial peptides. In this proposal, we join force with a biomedical research lab to develop new therapeutic agents to treat infections in the brain. The project aims to achieve this goal through three steps, all of which represent grand challenges in the field and demand sophisticated knowledge on chemistry and biology: first, the synthesis of the multi-modal peptide-polymer conjugate requires advanced chemical technology; second, the development of highest effective antimicrobial peptide-polymer conjugate with broad-spectrum efficacy against drug-resistance microbes but minimal toxicity towards mammalian cells requires thoughtful design and rounds of selection and optimization; third, delivering the macromolecular entities across BBB to distribute in the brain needs skilled animal manipulation, in-depth exploration and advanced imaging techniques. To meet these grand challenges, we three groups, chemical biologists, material scientists and biomedical researchers will collaborate seamlessly through the platform of this project.

The field nanomedicine has been booming in recent years with more and more breakthroughs emerging, although successful clinical applications are still on the way. The advancement of modern imaging techniques also opened the door to explore spatiotemporally how therapeutics interact with the pathogens in sophisticated organisms such as the brain. This project, during the course of solving grant challenges in a biomedical field, will also significantly advance the basic science of nanomedicine, esp. the basics of peptide nanoparticles.

Tensor Network States Approach to Frustrated Magnets and Unconventional Superconductivity

Hong Kong Principal Investigator: Prof Gu Zhengcheng (The Chinese University of Hong Kong)
Mainland Principal Investigator: Prof Chen Weiqiang (Southern University of Science and Technology)

In last three decades, it has become more and more clear that Landau symmetry-breaking theory fails to describe all possible orders in strongly correlated electron systems, such as frustrated magnets and unconventional superconductivity. The history of frustrated magnets can be traced back to P.W. Anderson’s resonating valence bond (RVB) scenario for an anti-ferromagnetic Heisenberg model on a triangular lattice. Due to the presence of geometric frustration, Anderson conjectured that the ground state of such a model must be a spin disordered state, and proposed that the ground state wave function can be described by superpositions of spin singlet valence bond patterns—the so-called RVB state. The term quantum spin liquid was later used to describe these kinds of exotic and intriguing quantum states. Quantum spin liquids describe new types of quantum matter beyond Landau’s paradigm, and are characterized by topological order and quantum order. Moreover, it has also been conjectured by P. W. Anderson that a doped Mott-insulator/spin liquid state might support intriguing unconventional superconductivity beyond the BCS scenario.

The theoretical investigation and experimental realization of quantum spin liquid in 2D and 3D frustrated magnets is currently a very important subfield in modern condensed matter physics. In the past decade, the investigation of quantum spin liquid has been extended to other frustrated magnets systems. Among the many interesting candidates, quantum spin-liquid like behavior has been observed experimentally in Herbertsmithite ZnCu3(OH)6Cl2, and it was believed that a simple Kagome antiferromagnetic Heisenberg model with a small Dzyaloshinskii-Moriya interaction term. Very recently, an intrinsic unconventional superconductivity was observed in a two-dimensional superlattice created by stacking two sheets of graphene that are twisted relative to each other by a small angle.

The PI and his collaborators have recently developed a novel numerical method to overcome the sign problem by combining the tensor network renormalization algorithm and the Monte Carlo sampling method. By fitting a universal scaling function, strong evidence for deconfined quantum critical point(DQCP) has been discovered in the square lattice J1-J2 model. The PI and collaborators have also begun to investigate the ground state phase diagram of honeycomb lattice tJ model, where intrinsic unconventional superconductivity has also been discovered. Here we propose to study (a) Tensor network states approach to frustrated magnets and the emergence of spin liquid (b) The mechanism of unconventional superconductivities in doped Mott insulator on honeycomb lattice (c) Properties of doped spin liquid and its experimental realizations.

Multi-functional Ion-exchange Membrane for Sulfur-based Batteries and Understanding the Charge Transport and Ion-immobilization Mechanism

Hong Kong Principal Investigator: Prof Lu Yi-chun (The Chinese University of Hong Kong)
Mainland Principal Investigator: Prof Huang Yaqin (Beijing University of Chemical Technology)

Electrochemical energy storage technology is attracting intensive research interest driven by the ever growing demand for high-energy and low-cost solutions for storing electricity. Sulfur-based energy storage technologies have received extraordinary research attention owing to their high gravimetric energy density (2-3 times that of the conventional Li-ion batteries) and promising potential for high-energy-density redox flow batteries. However, the life time and efficiency of sulfur-based storage devices are strongly limited by the dissolution of soluble polysulfide intermediates during cycling, the formation of insulating solid product such as lithium sulfide, and the formation of metal dendrite at the negative electrode. Developing low-cost ion-exchange membrane with high ion-selectivity and high ionic conductivity is one of the most critical challenges for sulfur-based electrochemical energy storage technologies.

In this project, we propose to develop highly-selective, conductive and low-cost ion-exchange membrane based on natural polymer chitosan and inorganic activators for high-energy metal-sulfur batteries. We design negatively charged glutamic acid-chitosan to selectively transport metal cations, to block the crossover of active anions such as polysulfide ions, and to suppress the formation of metal dendrite via increased cation flux sustained by surface conduction. We apply inorganic activators/carbon on one side of the membrane to facilitate the conversion of polysulfide to lithium sulfide. The proposed research work consists of four Tasks: (1) To develop structure-property-performance relationship of chitosan-based polymer membrane and large-scale fabrication technologies for low-cost, highly-selective and conductive ion-exchange membranes; (2) To develop structure-property-performance relationship of inorganic activators for efficient polysulfide absorption and conversion; (3) To develop ion-exchange membrane based on nanocomposites of chitosan-based polymer and inorganic activators to emulate the biological double membrane system; (4) To perform comprehensive investigations on the mechanical properties, stability, permeability, charge transport mechanism and origins of ion-selectivity/immobilization at the metal/polymer interfaces combining mechanical/electrochemical/molecular spectroscopic characterization techniques.

This project will yield fundamental insights into the structure-property relationship of ion-selectivity and ionic conductivity of the ion-exchange membranes; the structure-property relationship of the ion-immobilization and polysulfide conversion activity of inorganic activators; and charge transport mechanism and origins of ion-selectivity/immobilization at the metal/polymer interfaces. These fundamental insights will lead to the development of highly selective, conductive and low-cost cation exchange membranes for high-energy and efficient sulfur-based energy storage technologies.

Two-Dimensional Organic Semiconductors and the Related Device Applications

Hong Kong Principal Investigator: Prof Xu Jianbin (The Chinese University of Hong Kong)
Mainland Principal Investigator: Prof Wang Xinran (Nanjing University)

Research on 2D organic material based devices can not only provide a deeper understanding of the microscopic mechanisms of organic devices (e.g., transport properties at the interface and in 2D limit), but also provide a technological platform for the potential opportunities in numerous fronts ranging from electronics, optoelectronics to energy and sensing applications.

This project is targeted to design and fabricate high-performance electronic/optoelectronic devices based on 2D organic semiconductors and to explore their novel properties in 2D limit. In detail, we plan to develop van der Waals epitaxy techniques to realize the fabrication of large-area and high-quality two-dimensional organic semiconductors; to optimize the semiconductor/dielectric and semiconductor/metal interfaces; to develop large-area processing and integration techniques; to attain a better fundamental understanding and technical know-how for practical applications of two-dimensional organic semiconductors.

Roles of chromatin architecture in regulating allele-specific expression and male sterility in species hybrids

Hong Kong Principal Investigator: Prof Zhao Zhongying (Hong Kong Baptist University)
Mainland Principal Investigator: Dr Liu Xiao (Tsinghua University)

The underlying mechanism of hybrid male sterility or lethality, collectively called hybrid incompatibility, is a central question in evolutionary biology. One of the common hybrid incompatible phenotypes is manifested as the male sterility, in which misexpression of alleles especially male-specific ones from either of the parental species is frequently observed. However, it remains elusive how the allele-specific misexpression is produced in the hybrid sterile males. Intriguingly, male-specific genes are commonly enriched on the autosome but depleted on the X chromosome, suggesting a balanced interaction between the two is essential for male fertility. To characterize the molecular mechanism of hybrid male sterility, we propose to take advantage of a pair of nematode species, i.e., Caenorhabditis briggsae, a close relative of model organism C. elegans, which lives mostly as a hermaphrodite, and C. nigoni, which lives mostly as obligatory male and female. The two species can mate with each other and produce hybrid fertile females but sterile or dead males dependent on crossing direction. Unlike the hybrid F1 sterile males with C. nigoni as mother, whose genome is roughly equally contributed by both parental species, our previous work had showed that substitution of the right arm of C. nigoni X chromosome (also sex chromosome) with its counterpart in C. briggsae also produced male sterility in an otherwise C. nigoni background, indicating the integrity of X chromosome is essential for the male fertility. Surprisingly, our preliminary data show that presence of the same substitution leads to rescue of the hybrid F1 male sterility. Given the only difference between the sterile and fertile hybrid F1 males is the heterozygosity and homozygosity of the substituted C. briggsae chromosome fragment, respectively, we hypothesize that some aberrant interaction between the X-linked C. briggsae substitution and a C. nigoni autosome could exist, which leads to dysregulation of chromatin epigenetic landscape and subsequent allele-specific misexpression. The misexpression is likely to be responsible for the hybrid male sterility.

We will first characterize the short-range interaction within chromosome in the hybrid F1 sterile males, the rescued F1 fertile males and the parental males. We will next examine the epigenetic landscapes by profiling the permissive and inhibitive histone modifications in parental, hybrid F1 sterile and rescued fertile males. We will finally evaluate the allele-specific misexpression in the hybrid sterile and fertile males as well as in parental males. Integration of the chromatin architectural changes with the alterations in allele-specific expression will provide mechanistic insights into how chromatin domain organization and epigenetic modifications are perturbed in the hybrid background, which leads to dysregulation of allele-specific expression and hybrid male sterility. The results are expected to shed light on how chromosome architecture is programmed to define species boundary.

A mechanistic and clinicopathological study on the impact of invadosomes in promoting nasopharyngeal carcinoma (NPC) metastasis under the interplay of stromal macrophages and EBV infection

Hong Kong Principal Investigator: Prof Tsao George Sai-Wah (The University of Hong Kong)
Mainland Principal Investigator: Dr Li Xin (Southern Medical University)

Epstein–Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC) is characterized by high metastatic tendency. Its recurrence and distant metastasis after primary treatment remain the major causes for patient deaths. Invasive cancer cells can generate degradative membranous protrusions (called invadosomes) to degrade the surrounding extracellular matrix and to breach the endothelial layer of blood vessels for metastasis. NPC is known to be heavily infiltrated with tumor-associated macrophages (TAMs), which has been postulated to promote the invasive nature of NPC. EBV-encoded proteins or genes have also been suggested to contribute to the progression of NPC. However, the roles of TAMs and EBV infection in regulating the formation of invadosomes in NPC has not been explored.

Our preliminary data shows that M2-polarized macrophages (which resemble TAMs) could enhance the formation of invadosomes in nasopharyngeal cells without direct cell contact. In search for the secretary cytokine from M2-macrophages that mediated the invadosome generation of NPC cells, a membrane array of antibodies of cytokines was performed, and revealed that TNF-alpha was the major cytokine which could promote the invadosome formation and extracellular matrix degradation. We also found that M2-macrophages and TNF-alpha potently activated Src/cortactin pathway for signaling invadosome formation. In addition, M2-macrophages could stimulate the NPC cells to highly express an EBV-encoded latent membrane protein (LMP1). Expression of LMP1 could also upregulate the invadosome formation and activate Cdc42/N-WASP, which is a well-known activating complex for actin assembly in invadosomes. All these suggest an interactive role of the TAMs and EBV infection in promoting the invasiveness of NPC cells through modulating the formation of invadosomes. In this project, the mechanistic pathways underlying the regulation of invadosome formation in NPC will be elucidated in details. Live-cell imaging will also be exploited to record the dynamics of the degradative property of nasopharyngeal cells, and the temporal activation of signaling pathways. We have also established intravital imaging to visualize the cancer cells and their surrounding matrix and blood vessels in nude mice bearing dorsal skinfold window chamber (DSWC). To further investigate the stromal and invadosome components in disease progression and survival of NPC patients, we will conduct clinicopathological evaluation using our large cohort of NPC tissues and blood samples. By the joint forces of China and HK laboratories, this collaborative work will open up a new avenue to unveil the mechanism of invasion and metastasis of NPC, and identify new therapeutic strategies against the invasive spread of the disease.

Investigation on the immunological cross-protection between different human coronaviruses

Hong Kong Principal Investigator: Prof Peiris Joseph Sriyal Malik (The University of Hong Kong)
Mainland Principal Investigator: Prof Zhao Jincun (The First Affiliated Hospital of Guangzhou Medical University)

Coronaviruses came to global attention as significant human pathogens following the SARS outbreak in 2003. There are six coronaviruses that can cause human disease, viz. 229E, OC43, NL63, HKU1, MERS-CoV, SARS-CoV. MERS coronavirus (MERS-CoV) is the most recent coronavirus to emerge to threaten global public health. Little is known about the immunological cross-protection between these human coronaviruses. Most adults have been infected with multiple endemic human coronaviruses such as 229E, OC43, NL63, HKU1. While it is known that there is little serological cross-neutralization between there viruses, the role of cell mediated immune cross protection between coronaviruses is not known. If such cross-protection does exist, then pre-existing human coronavirus immunity may affect clinical outcomes following exposure to emerging viruses such as MERS or SARS-CV. Alternatively, does prior immunity enhance disease, as may sometimes occur with coronaviruses such as feline infectious peritonitis and flaviviruses such as dengue? What are the antibody mediated and cell mediated immune mechanisms by which such cross-protection or disease enhancement (if any) is mediated? These questions are addressed in this research proposal. Understanding these key knowledge gaps are relevant for understanding the epidemiology and pathogenesis of these important disease-causing viruses of humans and is relevant for development of vaccines against SARS and MERS-CoV.

Analysis of lipid metabolic pathways and gene regulatory networks in anther development in Arabidopsis and rice

Hong Kong Principal Investigator: Prof Chye Mee Lan (The University of Hong Kong)
Mainland Principal Investigator: Prof Zhang Dabing (Shanghai Jiao Tong University)

Sexual reproduction comprises a significant step in the life cycle of plants. To us, it represents a process at the end of which fruits and seeds, our major agricultural products, are generated from crop plants. A better understanding of sexual plant reproduction is necessary to map out strategies in increasing global food production in view of climate change and diminishing arable land. Lipids play an important role in pollen maturation and sexual reproduction. Although some enzymes/proteins in lipid metabolism, such as DPW/MS2, lipid transfer proteins (LTPs) and the acyl-CoA-binding proteins (ACBPs), have been proven essential for pollen wall development in flowering plants, their roles have not been comprehensively elucidated. The current proposal will continue from our previous investigations on the lipid metabolic pathways and gene regulatory networks in anther development, particularly on the functional mechanisms of proteins such as the ACBPs and lipid molecules in plant anther development. This will enable us better understand the process and decipher the differences from metabolites to evolution between monocots and dicots. A comparison in the functional variation and evolutionary conservation of the genes involved in pollen wall formation will be achieved by analysis of genome-wide data with bioinformatics tools. Findings from this project may lead to new genetic mechanisms on male sterility that would eventually yield novel strategies to create male sterile line materials in premium crops. In combination with cross-breeding, agricultural breeding breakthroughs could be achieved by the generation of male sterile lines in a simple and efficient manner.

Working mechanisms of TMC1 in auditory hair cells

Hong Kong Principal Investigator: Prof Huang Pingbo (The Hong Kong University of Science and Technology)
Mainland Principal Investigator: Prof Xiong Wei (Tsinghua University)

Auditory transduction is an important process for humans to obtain information from their surroundings. The mechano-electrical transduction (MET) complex in cochlear hair cells converts sound vibration into electrochemical signals in the nervous system. Compared with other special senses such vision and smell, our understanding of auditory transduction is less clear. Especially, the molecular identify of the channel responsible for MET remains unknown. TMC1 is a member of a family of 8 transmembrane proteins, which functions draw a lot attention recently. The MET response is completely eliminated in the hair cells of TMC1/TMC2 double knockout mice. In addition, the single channel conductance of MET channels is altered by a point mutation in TMC1's extracellular loop. These observations suggest that TMC1 might be the pore-forming subunit of MET channel. However, the precise function of TMC1 is still elusive, especially because the mechanosensitive channel activity of TMC1 has not been reconstituted in vitro. Here we propose to study TMC function and regulation using transcriptomic and proteomic analysis. We aim to understand the mechanism underlying the expression regulation and cellular function of TMC1 in hair cells, including protein synthesis/trafficking and mechanotransduction in stereocilia.

Study on structuralized cementing technology and innovative stone column-seawall system for environmentally friendly reclamation

Hong Kong Principal Investigator: Prof Wang Gang (The Hong Kong University of Science and Technology)
Mainland Principal Investigator: Prof Jin Feng (Tsinghua University)

The past decades have seen ever-increasing demand for reclamation of land from the ocean to expand the limited supply of developable land in highly populated coastal cities such as Hong Kong and Macau. With increasing awareness of environmental protection, conventional dredging methods cannot continue to be practiced, as excavating and dumping sea mud cause great disturbance and secondary pollution to seawater and marine ecology. Therefore, “non-dredged” reclamation methods without sea mud excavation have become crucial for minimizing impacts on the marine environment. Yet, stabilizing soft sea mud in situ is one of the key challenges in non-dredged reclamation. Several recent cases of failure in Hong Kong reclamation work reveal that conventional stone columns may not be effective for stabilizing soft sea mud. Therefore, there are calls for innovative materials and structures to address the key challenges.

This proposed study aims at providing a scientific basis and technical guidelines for innovative stone column-seawall system based on the newly invented Structuralized Cementing Technology (SCT) to address the urgent need for environmentally friendly “non-dredged” reclamation. SCT cements coarse aggregate using self- compacting concrete with no need for vibration or mixing, thus creating a broad spectrum of structurally cemented materials (SCMs). The SCMs have increased strength and stiffness, while maintaining the ductility and permeability of granular materials, making them promising for stabilizing soft sea mud in reclamation work.

Through collaborative research between HKUST and Tsinghua University, three inter-related tasks are planned. In Task 1, underwater filling technology will be researched to produce SCMs using environmentally friendly measures. To prevent cement leaking into seawater, a suitable underwater protective agent will be designed harmless to marine biology. The cement flow mechanism and various environmental factors influencing the formation of cementation structures will be studied to lay down a scientific basis for better understanding of the material. In Task 2, the micro- and macroscopic properties of SCMs will be studied using laboratory tests. Since the macroscopic performance of SCM is governed by the microscale structure of its cementation, a multiscale analysis framework will be developed for constitutive modeling of SCMs. Finally, structural analysis methods and guidelines will be proposed for designing a new stone column-seawall system using SCT. The state- of-the-art centrifuge modeling, prototype-scale wave flume testing and numerical simulation will be conducted to optimize the design of stone columns to stabilize soft sea mud, and to study wave energy dissipation mechanism of seawall under wave loading.

Searching for Majorana zero modes in topological crystalline insulator/superconductor heterostructures

Hong Kong Principal Investigator: Prof Liu Junwei (The Hong Kong University of Science and Technology)
Mainland Principal Investigator: Prof Jia Jinfeng (Shanghai Jiao Tong University)

Even with the rapid development as Moore’s law and their huge impacts on society and our daily life, classical computers still have their limitations and there are many problems far beyond their capacity. All information in classical computers is encoded using binary digits with one definite state (0 or 1), and the computations are governed by classical laws. On the contrary, a state in the quantum world can be a superposition of two distinct states (0 and 1), and its evolution is controlled by quantum laws. Intriguingly, by employing such quantum states one can build a quantum computer, which can efficiently solve many problems intractable in a classical computer. However, quantum states are very fragile and cannot be used in practice unless we find a way to stabilize them. One of the most promising approaches is to use topological quantum bits.

The topological quantum bit can be realized in a topological superconductor, which has, topologically protected zero-energy modes at the boundary described by Majorana zero modes (MZMs). One MZM has only half the degree of freedom of a usual fermion and a pair of MZMs can form a complete degree of freedom and represent a quantum bit. Moreover, MZMs can be separated spatially, thus the quantum states encoded in them cannot be affected by local perturbations. These novel properties make MZMs very suitable for the fault-tolerant quantum computation. Searching for suitable platforms for MZMs has become one of the most important topics.

In this project, we will explore the realization of MZMs in topological crystalline insulator/superconductor (TCI/SC) heterostructures. We will first study the novel properties of SnTe-type TCI thin films along [001] and [111] directions based on various theoretical calculations and experiments, and propose suitable SC materials for TCI/SC heterostructures. Then we will fabricate the proposed TCI/SC heterostructures in experiments. With suitable TCI/SC heterostructures ready, we can further study their properties under magnetic fields and demonstrate the existence of MZMs in vortices. Moreover, the unique properties of TCIs will allow us to study the effect of crystalline symmetries on MZMs and the interplay between different MZMs in TCI/SC heterostructures.

Passenger Mobility Analysis based on Car-hailing Platform Data and Artificial Intelligence Algorithms

Hong Kong Principal Investigator: Prof Yang Hai (The Hong Kong University of Science and Technology)
Mainland Principal Investigator: Prof Xiao Feng (Southwestern University of Finance and Economics)

With the maturity and popularity of Internet business patterns and intelligent mobile terminal hardware, ride-sourcing services have taken an unprecedented leap. The data collected by the online car-hailing platforms which account for a large proportion of the ride-sourcing market are of great value in estimating and forecasting passenger demand, traffic conditions and the management and optimization of traffic systems. However, in reality it is difficult to create value from the car-hailing platform data because it is hard to integrate data from different sources and establish a common model using traditional statistical approaches and theoretical models. The volume of data is also huge, complicating analysis. It should be processed using efficient data mining algorithms. And car-hailing data often involves complicated spatial-temporal information, so it is necessary to seek robust algorithms which effectively reduce the data’s dimensionality and deliver stable performance in the face of noise.

To address these difficulties, this proposed study will aim to develop novel deep learning and reinforcement learning algorithms and a combination of the two using data collected by DiDi Chuxing (DiDi for short). It will use the algorithms to explore passenger demand estimation, traffic state forecasting, and how to optimize dynamic dispatching of ride-sourcing cars on a large scale.

In the first part of the project, we will develop a two-step framework for real-time estimation of passenger demand from voluminous ride-sourcing data. A deep, graph-based convolutional neural network will be generated which captures passengers’ mobility patterns and constitutes a topological graph of passenger demand. In the study’s second phase we will collect time-domain and frequency- domain status information about vehicles serving DiDi’s car-hailing platform. Accurate estimation and prediction of traffic flows will then be realized using deep learning algorithms. In the third phase simulation of the spatial and temporal interdependence of traffic conditions and passenger demand will lead to creation of a deep reinforcement learning (DRL) algorithm which can optimize the dynamic dispatching of cars for ride-sourcing service. The study’s results will make both theoretical and practical contributions to the development of future smart and green ride-sourcing systems.

Study of a novel population of mammary stem cells arise during pregnancy

Hong Kong Principal Investigator: Prof Cheung Tom Hiu Tung (The Hong Kong University of Science and Technology)
Mainland Principal Investigator: Prof Zeng Yi (Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences)

The mammary gland is responsible for milk production and lactation and is critical for the successful reproduction and continuation of mammalian species. During puberty and pregnancy, hormones produced by ovaries promote development of the mammary gland and prepare it for milk production. Functions of the mammary gland are supported by various cell types originating from mammary gland stem cells. However, there are still debates about the identity of mammary gland stem cells and the process through which they give rise to other cell types.

Most of the previous studies were conducted on virgin mice. Given the fact that hormones released during pregnancy are potent regulators of the mammary gland, it would be interesting to investigate how the mammary gland stem cells are affected during pregnancy. We choose mice as our animal model as they offer the advantages of short development time and short gestation period, and because several genetic tools are available for this animal model, enabling investigation in a physiologically meaningful context. Our pilot investigation has discovered the emergence of an unknown stem cell population in the mammary gland during pregnancy. Importantly, these cells are able to generate new mammary glands. Based on their origin and characteristics, we have named them luminal-derived basal cells (LdBCs). These striking findings led to the following questions: 1) How do LdBCs arise? 2) What characteristics do they have? 3) How important are they? These questions will be addressed by the three aims of this proposal.

Combining the expertise of the Hong Kong team and the mainland team, animal study will be performed to determine the influence of ovarian hormones on the generation of LdBCs. High throughput sequencing will delineate the underlying molecular mechanisms. Global gene expression profiles will also be elucidated to score the similarities and differences between LdBCs and other mammary gland cells. For functional aspects, our project will also explore the roles played by LdBCs in the normal mammary gland and the development of breast cancer. We believe that the successful completion of this project will not only enhance our understanding of mammary gland stem cells, but also lay the foundation for the development of novel and more effective strategies and therapeutics to combat breast cancer in the long run.

Study of the optimal encapsulation of customized shear thickening fluids and their energy absorption mechanisms in composites

Hong Kong Principal Investigator: Prof Yang Jinglei (The Hong Kong University of Science and Technology)
Mainland Principal Investigator: Prof Zhang Zhong (National Center for Nanoscience and Technology)

A shear thickening fluid (STF) is a non-Newtonian liquid containing suspended nanoparticles. Its viscosity increases rapidly at a certain threshold strain rate, making the fluid to behave like a solid. STFs have been adopted to design and develop impact-resistant and energy-absorbent materials, for example, flexible liquid body armor. However, it’s very challenging to utilize STFs beyond in fabrics or porous materials due to their liquidity, hydroscopicity, leakage, degradation of the host material, etc. To overcome these disadvantages and extend STFs’ full capacity in other areas, we propose a direct encapsulation method for STFs to make them as easy-to-handle powders and to investigate their energy absorbing mechanisms individually and in a model composite system through both experimental and numerical methods. The study is motivated by the academic and practical importance of a basic understanding of the shear thickening effectiveness in discrete form and by the need to design and apply a wide range of encapsulated STF composites and structures for impact resistance and effective energy absorption.

Mechanistic studies of the obesity-induced abnormal purine nucleotides in muscle repair and regeneration

Hong Kong Principal Investigator: Prof Wu Zhenguo (The Hong Kong University of Science and Technology)
Mainland Principal Investigator: Prof Zhang Jianfa (Nanjing University of Science and Technolofy)

Obesity and diabetes are prevalent metabolic disorders that affect millions of people world-wide. It is known that the tissue repair and regenerative abilities decrease in both diabetic patients and animal models. The underlying mechanisms are poorly defined. Based on both the published and preliminary data from Prof. Jianfa Zhang’s group, plasma 5’-AMP levels were found to be elevated in both high fat diet-induced obese mice and diabetic mouse models. Injection of 5’-AMP into normal mice recapitulates multiple metabolic defects seen in diabetic mice. In this proposal, we will focus on the effects of extracellular 5’-AMP on erythrocytes, skeletal muscles, and muscle stem cells. In particular, we will examine how high levels of free fatty acids or triglycerides in obese/diabetic mice trigger the extracellular release of 5’- AMP from erythrocytes. We will also study the impact of extracellular 5’-AMP on metabolic, signaling and functional status of skeletal muscles. Then, we will focus on the impact of 5’-AMP on muscle stem cells and injury-induced muscle regeneration in vivo. In particular, we will examine the impact of 5’-AMP on the PI3K/mTORC1/FoxOs signaling pathway in muscle stem cells as this pathway is known to be indispensable for muscle stem cell function during muscle regeneration. Through this proposal, we hope that we will have a better understanding of the role of 5’-AMP on skeletal muscles and muscle stem cells under the obese and diabetic conditions.

Fundamental Study on Turning of Incineration Sewage Sludge Ash (ISSA) and Heavy Metal Contaminated Sediment from Rivers or Coastal Areas as Low-carbon and Eco-friendly Construction Materials

Hong Kong Principal Investigator: Prof Poon Chi-sun (The Hong Kong Polytechnic University)
Mainland Principal Investigator: Prof Xue Qiang (Institute of Rock and Soil Mechanics (IRSM), Chinese Academy of Sciences (CAS))

Safe treatment and recycling of heavy metal contaminated sediment from lakes, rivers and marine environments is a major environmental and engineering problem and has attracted considerable attentions in Hong Kong and mainland China. The lack of disposal ground (both marine and land based) drive governments to explore reuse options of the sediments. Separately, due to increasing amounts of sewage sludge generation in modern cities from increasing number of sewage treatment plants, advanced incineration technology is being promoted as a sustainable means of managing the dewatered sewage sludge. Therefore, developing sustainable incinerated sewage sludge ash (ISSA) re-use methods is of significant importance. Currently the ISSA is being disposed of at landfills. Based on previous research findings, ISSA does possess some levels of pozzolanic activity and water/metals affinity which may be utilized as a binder in the chemical stabilization/solidification of hazardous waste or sediment.

The feasibility of using the ISSA as a stabilizing/solidification (S/S) agent for the contaminated sediment is the major focus of this proposed study. In this project, multidisciplinary theories of civil engineering materials, soil mechanics and environmental engineering will be adopted to develop low cost and low embodied carbon binders for S/S process. Two potential binder systems are suggested; (i) ISSA/lime cementitious binder, (ii) ISSA geoploymer binder. Firstly, the optimal lime-ISSA/geopolymer-based ISSA binders will be developed by investigating the change of engineering and heavy metal leaching properties of the solidified/stabilized sediments with and without pre-treatment (e.g.: sieving to separate the silt and clay from sand in the sediment, and alkalization or heating to remove organic matters etc.). Secondly, the mechanisms of the strength development and heavy metals immobilization will be studied by a series of microstructure, spectroscopy analysis and molecular dynamic modelling. Thirdly, the durability of the produced construction materials will be explored by a range of accelerated and long-term tests, including carbonation, water immersion, dry-wet cycle, and thawing-freezing cycles. Lastly, new visco-elastoplastic damage model and leaching prediction models will be established and validated for simulation of the time-dependent behaviour of the stabilized sediment. The findings will be of great significance for the development of scientific theory and low cost S/S systems for the treatment of contaminated sediment in Hong Kong and mainland China.

Active Heat Transfer Enhancement Method of Paraffin Thermal Storage by Foam Structure Together with Vibration Particles

Hong Kong Principal Investigator: Dr Lu Lin (The Hong Kong Polytechnic University)
Mainland Principal Investigator: Prof Wang Qiuwang (Xi'an Jiaotong University)

The instability and intermittency of renewable energy sources, such as solar energy and wind energy, greatly restrict their applications in the current energy power systems. To promote the utilization of renewable energy, energy storage becomes a key technical issue. Generally, there are several different types of energy storage, such as electrical, mechanical, chemical and thermal energy storage. Latent thermal storage (LTS) which using phase change materials (PCMs) is one of the most promising, featured by high-energy storage ability, controllability of phase change temperature and reutilization.

However, the low thermal conductivity and the low convective heat transfer of traditional PCMs result in poor heat transfer performance, low thermal storage efficiency and large volume of storage system. Accordingly, both passive enhancement method and active enhancement method can be employed to improve the thermal storage performance. Inserting solid porous skeleton into PCMs was commonly attempted to improve the thermal conductivity, but the only addition of porous structure has its limitation due to reduction of pure PCMs and obstruction of natural convection. Active method was seldom examined.

Therefore, for the common PCM of paraffin, this project aims to newly develop an active combined approach to improve its LTS performance and reliability. The newly proposed paraffin LTS system will be developed based on the previous solid porous skeleton phase change thermal system but novel active enhancement methods of ultrasonic vibration and vibration particles will be firstly introduced. This project can provide valuable guidance and high performance energy storage solutions for achieving reliable renewable energy and distributed energy systems.

Deciphering the Mechanisms of Action of Phosphoethanolamine Transferase, MCR-1, A Colistine Resistance Protein and Development of Transitional State Inhibitors

Hong Kong Principal Investigator: Prof Chen Sheng (The Hong Kong Polytechnic University)
Mainland Principal Investigator: Prof Yu Biao (Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences)

Emergence of colistin resistance in clinical carbapenem-resistant Enterobacteriaceae (CRE) strains undermines the value of colistin as the last resort antimicrobial agent in treatment of infections caused by CREs. It is therefore urgent to develop inhibitors of this type of enzymes to preserve the therapeutic efficacy of polymyxin. However, a lack of understanding of the mechanism of action of these enzymes due to the difficulty in structural characterization of membrane proteins with double lipids, prevented the development of effective inhibitors. This study aims at depicting the mechanism of action of MCR-1, a colistin resistance determinant discovered in 2015, and developing effective substrate-based and transitional state MCR-1 inhibitors. MCR-1 is aphosphoethanolamine (PEA) transferase that modifies bacterial lipid A through installation of the PEA moiety. To unveil its mechanism of action, we propose to conduct mutational analysis of important residues located in three domains, the enzymatic domain (ED), transmembrane domain (TMD) and the loop region linking ED and TMD, to identify important residues involved in substrate binding and catalysis. We shall also investigate the substrate requirement for MCR-1 through testing different analogues of its substrates, namely phosphatidylethanolamine (PE) and lipid A. Upon complete delineation of the mechanisms of action of MCR-1 and its substrate requirement, we shall develop substrate-based and transitional state-based inhibitors. First, residue T285 of MCR-1 is currently known to play a crucial role in transferring PEA from PE to lipid A. Thus, a compound that can mimic PE and covalently interact with T285 may act as MCR-1 inhibitor. We propose to design and synthesize PE-like molecules and test their ability to compete with PE binding. Second, PEA-based inhibitors will be developed based on the mode of interaction between MCR-1 and PE. Third, lipid A analogues will be synthesized to test the effects of blocking the binding of lipid A to MCR-1. Compounds of high inhibitory potential will be subjected to assessment of toxicity, pharmacokinetic / pharmacodynamic parameters, and antimicrobial efficacy when used in combination with colistin in animal models, in a hope to restore the clinical value of colistin as a last-line antibiotic for treatment of infections caused by multidrug resistant bacterial pathogens.

Exploring High-temperature Superconductivity in Layered-structure Iridates Through Atomic and Magnetic Structure Tuning

Hong Kong Principal Investigator: Dr Zhu Ye (The Hong Kong Polytechnic University)
Mainland Principal Investigator: Prof Nie Yuefeng (Nanjing University)

High-temperature superconductivity (HTS) has so far only been discovered in copper- and iron-based materials, and its underlying mechanism remains unclear. Exploring new HTS materials holds the key to better understand this fascinating phenomenon and may lead to revolutionary applications in power transmission, magnetic levitation and quantum computing. Recently, an unusual type of HTS with 5d electron Cooper pairs was predicted in iridates, which has attracted significant interest. However, so far HTS has not been experimentally observed in iridates, which is attributed to the intrinsic structural distortions and defects that suppress HTS. To experimentally demonstrate the novel 5d HTS, we aim to fabricate high-quality iridates with structural distortions and defects inhibited through structure engineering. We will utilize a combination of cutting-edge molecular beam epitaxy (MBE) and atomic-scale scanning transmission electron microscopy (STEM). Our expertise in oxide MBE growth allows us to grow ultrathin iridate films with minimized disorder. Structure engineering on such ultrathin films will be achieved by using the appropriate substrates and doping approach. The quality of the iridate films will be examined using atomic-resolution STEM, the only technique that can sensitively image structural distortions and defects in ultrathin films. Such structure-engineered iridates will present a unique system on which HTS can be explored through transport and magnetism measurements, as well as spectroscopy studies. The 5d HTS, if successfully identified, will add a new branch to the HTS family and provide critical insights to the long-standing conundrum of HTS mechanism.