Congratulations to two faculty members from the School of Science who have been recognized by the National Natural Science Foundation of China (NSFC)! Prof. Zhigang BAO, Associate Professor in the Department of Mathematics, and Prof. Ding HE, Assistant Professor in the Department of Ocean Science, both named NSFC Excellent Young Scientists (Hong Kong and Macau), have received a funding of RMB 2,000,000 to support their scientific research projects for a period of 3 years. Only 25 projects across Hong Kong and Macau have been awarded this highly competitive fund this year.
Prof. Zhigang BAO has been awarded with his research project titled “Random Matrix Theory and its applications in Statistics”. It focuses on studying the spectral theory of large dimensional random matrices. It would investigate the limiting behavior of eigenvalues and eigenvectors of random matrix models arising from free probability, disordered quantum system, and multivariate statistics.
Prof. BAO’s research:
Prof. Ding HE has been awarded with his research project titled “Organic Geochemistry of Estuaries and Coasts”. Estuaries and coasts, linking land and ocean, play a critical role in global carbon cycle, but traditional methods cannot resolve the carbon source/sink processes. Based on molecular biomarkers, stable isotopes, ultra-high resolution mass spectrometry, and big-data techniques, Prof. HE focuses on the organic carbon (OC) cycling in estuaries and coasts. In particular, he determined the OC sources, biogeochemical processes, and the underlying controlling factors during the Anthropocene and published over 50 manuscripts in international journals. With support of the fund, Prof. HE and his group members aim to reveal the OC burial process, carbon sequestration capacity and control factors from the molecular level, serving the national and Hong Kong government’s carbon peak, and carbon neutral policy needs.
To our best knowledge, Prof. HE is the first awardee of this fund in the field of Oceanography (especially in Chemical Oceanography) in Hong Kong and Macau.
The organic carbon cycling in estuaries and coasts (partially reorganized from Bauer et al., 2013)
The DREAM (Data-driven Research for Exploring Aquatic geocheMisty) group in Department of Ocean Science, HKUST (www.helabhkust.com)
Prof. Haipeng LU, Assistant Professor in the Department of Chemistry has been awarded the 2022 National Natural Science Foundation of China (NSFC) Young Scientists Fund. This prestigious fund offers support to young academics and encourages them to focus on a self-chosen area for basic research. It helps foster the young scholars with outstanding achievement on the international science frontiers.
Prof. Haipeng LU is awarded for his research project titled “Development of highly luminescent chiral hybrid semiconductors”. The development of polarized light sources plays an essential role in the modern display industry and future technologies including 3D display, quantum computing and sensing, and information processing. Current materials and approaches that generate polarized light have serious limitations including excessive cost, complex infrastructure, and low sensitivity and resolution. This project is focused on the development of an emerging family of hybrid semiconductors that break the time-reversal symmetry via structural chirality. These materials have the potential to emit high purity of circularly polarized luminescence with high efficiency. This project is to build such a synthetic roadmap for these fascinating materials.
Congratulations to Prof. LU on receiving the 2022 NSFC Young Scientists Fund!
Prof. Haipeng LU (fourth from the left) and his group members
The Hong Kong University of Science and Technology (HKUST) held the Sixth Inauguration Ceremony of Named Professorships today to honor eight outstanding faculty members and their donors.
Officiating at the ceremony, HKUST Council Chairman the Hon. Andrew LIAO Cheung-Sing said, “Every year, the University’s Named Professorships program attracts and retains globally recognized scholars working on increasingly challenging and diverse topics — in line with HKUST’s efforts to promote innovative research across the borders of science and engineering, business, humanities, and social sciences. I extend my most sincere gratitude to our donors and my warmest congratulations to the 2022 cohort of HKUST Named Professors — the latest torch-bearers for the University’s unrelenting pursuit of academic excellence.”
HKUST President Prof. Wei SHYY also congratulated the appointed faculty members and thanked the donors’ generous contribution. “Since the program’s launch in 2013, we have awarded the title of Named Professor to more than 50 eminent faculty members, whose award-winning research and inspiring teaching are shaping a better world for future generations. We express our heartfelt gratitude to the donors who have supported HKUST over the years—particularly those who have given the gift of a professorship. Thanks to their generosity, we are able to recognize, reward, and retain intellectual leaders in a wide spectrum of disciplines and support our faculty members and the University as a whole in scaling new heights.”
The expertise of the eight named professors covers a wide spectrum of research areas including particle physics, computational materials science, material physics, stem cell biology, quantum simulation, cancer genomics, data science, as well as sales and marketing innovation.
The professorships were made possible by donations given to HKUST from long-standing contributors to higher education including Shun Hing Education and Charity Fund, Kerry Holdings Limited, Dr the Hon. Hari Harilela and Mrs Padma Harilela, Otto Poon Charitable Foundation and anonymous contributors, and by funds set aside by the University.
Among the officiating guests at the Inauguration Ceremony were HKUST Council Chairman the Hon. Andrew LIAO Cheung-Sing, President Prof. Wei SHYY and other senior management. Donors and their representatives also attended the ceremony, including Ms. Vinita CHONG, Mr. Thomas LUI, Dr. Aron HARILELA, Miss Pat POON and Mrs. Teresa CHAN.
The named professors are:
IAS Paul C W Chu Professor
Prof. Kam-Biu LUK, HKUST Jockey Club Institute for Advanced Study (IAS)
Dr William M W Mong Professor of Nanoscience
Prof. Xi DAI, School of Science
Wu Chien-Shiung Professor of Science
Prof. Jiannong WANG, School of Science
Kerry Holdings Professor of Science
Prof. Ting XIE, School of Science
Hari Harilela Associate Professor of Physics
Prof. Gyu-Boong JO, School of Science
Padma Harilela Associate Professor of Life Science
Prof. Jiguang WANG, School of Science
Otto Poon Professor of Engineering
Prof. Xiaofang ZHOU, School of Engineering
Yuk-Shee Chan Professor of Business
Prof. Mengze SHI, School of Business and Management
An international research team, led by Prof. Nancy IP, The Morningside Professor of Life Science at the Hong Kong University of Science and Technology (HKUST) and Director of the Hong Kong Center for Neurodegenerative Disease (HKCeND), has identified a blood protein that plays a key role in the pathogenesis of Alzheimer’s disease (AD). Their findings reveal an innovative strategy in reducing the risk of AD development and ameliorating disease pathologies in individuals living with AD.
AD, which affects over 50 million people worldwide, is currently an irreversible condition that lacks effective treatment. This is primarily because the disease mechanisms are complex and largely unclear, with few effective targets available for drug development. Researchers have previously observed that impaired clearance of the toxic amyloid-beta (Aβ) peptides in the brain of AD patients by the immune cells (microglia) causes cellular dysfunction, resulting in memory loss and cognitive problems. Yet, the reason behind this impairment is still not well known.
Now, the team has discovered a blood protein, soluble ST2 (sST2), that plays a key role in disrupting Aβ clearance by microglia. The team showed that sST2 levels increase in the blood and the brain during aging, thereby perturbing the activities of the cytokine interleukin-33 (IL-33), leading to reduced microglial clearance of Aβ and thus elevated Aβ deposition. The team had, in fact, previously discovered the beneficial activity of IL-33 on microglial clearance of Aβ in the brain. Interestingly, they further found that reduced sST2 levels confer a protective effect against AD development, and ameliorate AD-related pathologies in individuals who have developed the disease.
The research team further discovered that sST2 levels are regulated by genetic factors. Individuals carrying a genetic variant termed “rs1921622” show comparatively low sST2 protein levels in the blood and the brain even when they age, and have a lower chance of developing AD. This is particularly evident in women carrying the APOE4 gene, the strongest genetic risk factor of AD. As revealed in postmortem brain studies by the team, carriers of this protective genetic variant displayed significantly alleviated AD-related pathologies, marked by lower Aβ plaque deposition, reflecting better Aβ clearance by microglia in the brain.
Taken together, these critical findings open up new possibilities for the therapeutic treatment of AD that are primarily aimed at decreasing sST2 levels. This innovative strategy only requires manipulation of the protein in the blood, and thus offers a simpler and safer approach compared to other therapeutic strategies that target the brain. Particularly, it gives hope to high-risk groups such as female APOE4 carriers, who tend to bear a higher risk of AD development and exhibit more severe symptoms after developing the disease, accounting for 25% - 50% of all AD patients.
“While this exciting work has further improved our understanding of AD, and identified an excellent drug target for developing therapeutics, it has also made clear the importance of precision medicine in tackling this complex, multi-factorial disease,” said Prof Ip. “The next step is to develop clinical interventions that target sST2 and determine their viability as effective AD preventatives and treatments, especially for female APOE4 carriers who are at high risk of developing AD.”
The work was conducted with the support from the InnoHK scheme of the HKSAR government and undertaken in collaboration with researchers at University College London and Stanford University, clinicians at the Prince of Wales Hospital, the University of Melbourne, and Edith Cowan University. The results were recently published in the prestigious journal Nature Aging, and have also been featured and actively discussed on various scholarly exchange platforms focused on AD research such as Alzforum.
A research team at The Hong Kong University of Science and Technology (HKUST) has developed a new electrode design that is set to enable the rechargeability of alkaline zinc batteries, one of the most common types of non-rechargeable batteries used in our daily lives, shedding light on a wider application of rechargeable batteries.
Batteries are ever important in the age of smart cities and global digitalization. Yet, a majority of batteries in the market are not rechargeable, or called primary batteries. They are disposed after a single use, an unsustainable practice that poses a serious threat to the environment.
Compared with other types of primary batteries, alkaline zinc batteries are cheap, safe, and energy-dense. They are used in many household items such as flashlights and remote controllers. Given the advantages, there is never a lack of effort from researchers worldwide trying to make alkaline zinc batteries rechargeable.
Yet, such effort has been falling short because the battery reaction of zinc is hardly reversible. When the battery is discharged, zinc particles in the zinc electrode are covered with a thick and non-uniform layer of insulating zinc oxide, losing the metal surface and electric conductivity, both necessary for the electrode to be recharged.
To tackle the issue, a research team led by Prof. CHEN Qing from the Department of Mechanical & Aerospace Engineering and Department of Chemistry at HKUST developed a nanoporous zinc metal electrode that is capable of stabilizing the electrochemical transition between zinc and zinc oxide, successfully turning an alkaline zinc-air coin cell, a type of primary battery usually found in hearing aids, into a rechargeable battery stable for over 80 hours. The team shaped zinc into curvy filaments hundreds of nanometers wide, nested in a freestanding solid with numerous, similarly narrow pores. When the battery is discharged, a thin layer of zinc oxide nucleates on the zinc filaments, preserving the metallic network and enabling the zinc electrode to return to its initial structure.
The team also tested out the nanoporous zinc electrode in alkaline nickel-zinc batteries, a kind of uncommon secondary zinc battery which normally offer 50-80 times of discharging and charging under a condition competitive against the state-of-the-art lithium-ion batteries. The result demonstrated a multi-fold increase to over 200 times.
“The needs for batteries are diverse and difficult to be met by a single technology. Zinc batteries are finding their niche. We just need to make sure that the microstructure of the zinc electrodes can withstand hundreds, and hopefully thousands, of times of discharging and charging when getting the most energy out of the batteries,” said Prof. Chen. “Our work achieves so by understanding and then designing how atoms organize themselves at the liquid-solid interface that is manifested by the nanoporous structure, which has been applied to address a range of technological challenges,” he explained.
Prof. Chen added that while a few hundred times of discharging and charging may not seem many, alkaline zinc batteries have an edge in safety and low cost, which are ideal for industrial applications such as golf carts and forklifts. They also suit emerging applications, for example, the backup power of data centers, which do not demand many times of discharging and charging but require the battery to be extremely safe.
Prof. Chen’s group has been working with industrial partners since the beginning of the research in 2018 and will continue engaging them for the commercialization of the promising technologies.
The team’s research work was recently published in Nature Communications.
Led by Prof. Chen, the team included postdoctoral fellow Dr. LI Liangyu, former research assistant Anson TSANG Yung-Chak, PhD student XIAO Diwen, former postdoctoral fellow Dr. ZHU Guoyin, as well as Prof. ZHI Chunyi from the City University of Hong Kong.
To: DSE students,
While you are waiting for the release of DSE results, you may wish to learn more about some tips for admitting to our science programs through JUPAS scheme for 2022 intake.
We have conducted a series of JUPAS Program Consultation sessions for DSE candidates in July which you might have joined. Through these online sessions, we hope to provide you with the latest admissions information such as the expected scores and flexible admissions arrangements. You would find these very helpful during your consideration of modifying your program choices after the release of DSE results.
Here below are some footages and PPT files to enhance your understanding of our offerings at the School of Science including the undergraduate programs, majors, credit transfer, exchange and internship opportunities, and student life at HKUST. You are also strongly advised to pay attention to the updated admissions timeline.
Undergraduate Admissions for 2022 intake
We highly recommend you to check out the links for the 2022 JUPAS Program Consultation on SSCI programs if you have missed the LIVE broadcasting on 8 & 11 July.
- presented by Prof. Tim LEUNG - Associate Dean (Student Recruitment)
- presented by Ms. Shirley PANG - Manager (Student Recruitment and Admissions)
- presented by Ms. Tina KO - Manager (Student Advising)
Program Highlights (2022 intake): Relevant programs’ information are now available on our webpages listed below:
IRE Graduate Sharing:
- Master program of Quantum Information Processing at Technical University of Munich Walther-Meissner-Institute
- BSc in Physics (International Research Enrichment Track), with an additional major in Mathematics, Class of 2020
- MPhil program in Life Science at HKUST
- BSc in Biochemistry and Cell Biology (International Research Enrichment Track), Class of 2021
SSCI Alumni Sharing:
- Master program in Materials Science and Engineering at Kyoto University
- BSc in Physics, Class of 2020
- Associate Manager, Lee's Pharmaceutical (Holding) Limited
- BSc in Biochemistry, Class of 2013
- Chemist, The Hong Kong Electric Co. Ltd.
- BSc in Chemistry, Class of 2014
Look forward to seeing you at HKUST in September!
Structural biologists at The Hong Kong University of Science and Technology (HKUST) together with researchers at the AIDS Institute, The University of Hong Kong (HKU), Department of Microbiology, School of Clinical Medicine, the LKS Faculty of Medicine of The University of Hong Kong (HKUMed) and the State Key Laboratory of Emerging Infectious Diseases, HKU have demonstrated that ZCB11, a broadly neutralising antibody derived from a local mRNA-vaccinee against the spreading Omicron variants of SARS-CoV-2, displays potent antiviral activities against all variants of concern (VOCs), including the dominantly spreading Omicron BA.1, BA1.1 and BA.2. Critically, either prophylactic or therapeutic ZCB11 administration protects lung infection against Omicron viral challenge in golden Syrian hamsters. The research paper is now published online in Nature Communications (link to publication).
The strikingly high transmissibility and antibody evasion of SARS-CoV-2 Omicron variants have posed great challenges to the efficacy of current vaccines and antibody immunotherapy. In response to the continuous emergence of SARS-CoV-2 Omicron variants with unpredictable pathogenicity, universal masking, quarantine and endless viral testing have to be maintained, resulting in social anxiety and economic disruption. It is therefore important to investigate into whether host immune response can generate broadly neutralising antibodies, which is essential not only for antibody-based immunotherapy but also for vaccine optimisation to induce equally broad protection.
Research methods and findings
In this study, the HKUMed team has established an effective platform of cloning technology that natively pairs antibody genes from individual human memory B cells. Using this technique, the research team successfully discovered ZCB11 after screening 34 BNT162b2-vaccinees in Hong Kong, and demonstrated that ZCB11 neutralises all VOCs including Alpha (B.1.1.7), Beta (B.1.351), Gamma (P1), Delta (B.1.617.2) and Omicron (B.1.1.529) by testing both pseudoviruses and authentic live viruses. Importantly, ZCB11 administration protects lung infection against both live Omicron and Delta viral challenges in golden Syrian hamsters respectively, under both prophylactic and therapeutic conditions. Furthermore, the HKUST collaborative team deciphered the complex structure of ZCB11 and spike protein at atomic resolution using single particle cryo-EM, revealing the unique molecular mode of ZCB11 action, which lays a solid foundation for upcoming structure-guided antibody and vaccine optimisation.
Significance of the study
“The findings suggested that ZCB11 is a promising antibody drug for biomedical interventions against pandemic SARS-CoV-2 variants of concern,” remarked Professor CHEN Zhiwei, Director of AIDS Institute and Professor of the Department of Microbiology, School of Clinical Medicine, HKUMed, who led the study. “Although our findings implicate that the HKUMed team is at the world’s forefront of research and development of human antibody drugs and vaccines against COVID-19, we still urgently need to establish large-scale manufacturing capacity and clinical translational hubs in Hong Kong, in order to meet its aspiration of becoming an international innovation centre.”
“The high-resolution structural information enabled us to understand the molecular mechanism of ZCB11 responding to a broad SARS-CoV-2 variant of concern,” said Professor DANG Shangyu, Assistant Professor of Division of Life Science, HKUST. “This study relies on the state-of-the-art cryo-EM facility at HKUST, which demonstrated its capability to support not only research in structural biology, but also many other research fields, such as antibody development in this study.”
About the research team
The research is led by Professor Chen Zhiwei, Director of AIDS Institute and Professor of the Department of Microbiology, School of Clinical Medicine, HKUMed; and was conducted primarily by Mr. ZHOU Biao, PhD candidate. Dr. ZHOU Runhong, research officer; Dr. Jasper CHAN Fuk-Woo, Clinical Associate Professor; LUO Mengxiao and PENG Qiaoli, PhD candidates; Dr. YUAN Shuofeng, Assistant Professor at the Department of Microbiology, School of Clinical Medicine, HKUMed. TANG Bingjie and LIU Hang, MPhil students of Division of Life Science, HKUST, shared the first authorship.
This collaborative team also includes Dr. Bobo MOK Wing-Yee, Scientific Officer; CHEN Bohao; Dr. WANG Pui, Scientific Officer; Dr. Vincent POON Kwok-Man; Dr. CHU Hin, Assistant Professor; Chris CHAN Chung-Sing, Jessica TSANG Oi-Ling, Chris CHAN Chun-Yiu, AU Ka-Kit, MAN Hiu-On, LU Lu, Dr. Kelvin TO Kai-Wang, Chairperson and Clinical Associate Professor; Professor CHEN Honglin; Professor YUEN Kwok-Yung, Henry Fok Professor in Infectious Diseases and Chair of Infectious Diseases, Department of Microbiology, School of Clinical Medicine, HKUMed and Director of the State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong. Professor Dang Shangyu and Professor Chen Zhiwei shared the correspondence authorship.
This study was supported by the Hong Kong Research Grants Council - Collaborative Research Fund (C7156‐20GF, C1134‐20GF and C5110‐20GF) and Health and Medical Research Fund from the Food and Health Bureau (19181012); Shenzhen Science and Technology Program (JSGG20200225151410198 and JCYJ20210324131610027); the Hong Kong Health@InnoHK, Innovation and Technology Commission, the Government of the Hong Kong Special Administrative Region; and the China National Program on Key Research Project (2020YFC0860600, 2020YFA0707500 and 2020YFA0707504); and donations from the Friends of Hope Education Fund in Hong Kong. Professor Chen Zhiwei’s team was also partly supported by the Hong Kong Research Grants Council - Theme‐based Research Scheme (T11‐706/18‐N) and Wellcome Trust P86433.
All cryo-EM data were collected at the Biological Cryo-EM Center at HKUST, generously supported by a donation from the Lo Kwee Seong Foundation, together with support to Professor Dang Shangyu’s team from the Research Grants Council (RGC) of Hong Kong (ECS26101919, GRF16103321, C7009-20GF, C6001-21EF), Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou) (SMSEGL20SC01-L), Guangdong Basic and Applied Basic Research Foundation (2021A1515012460), Shenzhen Special Fund for Local Science and Technology Development Guided by Central Government (2021Szvup140) and HKUST start-up and initiation grants.
About HKUST Biological Cryo-EM Center
With a generous donation from the Lo Kwee Seong Foundation, the HKUST Biological Cryo-EM Center (//cryoem.hkust.edu.hk/) was established to allow local scientists to study biological macromolecules at atomic resolution. Currently, the Center hosts the modern state-of-the-art microscope, including Titan Krios, K3 direct electron detector and several other high-end equipment, providing dedicated users’ access to single particle analysis and cryo-electron tomography with technical supports.
About the Department of Microbiology, HKUMed
The academic staff of Department of Microbiology are actively involved in clinical service and basic research. Postgraduate students may pursue studies on various aspects of microbiology and infectious diseases leading to an MPhil or PhD degree. The Master of Medical Sciences programme offers an opportunity to postgraduates interested in more in-depth studies on the biomedical aspects of clinical microbiology and infectious disease. In addition, the clinical staff of the Department also participate in the training of clinical microbiologists in Hong Kong and Shenzhen. The Infectious Disease Courses and Postgraduate Diploma Programme provides a unique avenue for the training of qualified medical practitioners in infectious diseases.
To promote knowledge exchange, research activities at the Department of Microbiology, School of Clinical Medicine, HKUMed can be viewed through http://www.microbiology.hku.hk/.
(This article was originally published on EurekAlert! on June 17, 2022)
A research team led by Prof. GAN Jianping, director of the Center for Ocean Research Hong Kong and Macau (CORE) at The Hong Kong University of Science and Technology (HKUST), carried out field observations and conducted numerical simulations in the South China Sea (SCS) recently and revealed the never-before-seen characteristics of the three-dimensional ocean motion in the SCS through geophysical fluid dynamic theory. The complex ocean circulation system controls the energy conversion and water mass transport in the SCS, subsequently affects the biogeochemical processes, carbon budget, marine ecological environment health, regional climate change, and the sustainable economic and social development in surrounding countries and regions, which accounts for about 22% of the world's population. Studies on the SCS circulation and dynamics are regarded as the foundation and epitome of understanding the SCS.
In the past few decades, there has been growing global attention to ocean circulation research in the SCS. However, scientific understanding of the three-dimensional water movement in this region is still very limited, ambiguous, and sometimes even misunderstood. This is caused by the lack of observations, reliable numerical model, and the knowledge of the complicated physical processes in the SCS circulation.
Until recently, based on observations, numerical simulations, and geophysical fluid dynamics reasoning, a research team led by Prof. Gan, who is also Chair Professor at HKUST’s Department of Ocean Science and Department of Mathematics, validated that the SCS rotating circulation has a three-layered structure, where currents rotate counterclockwise, clockwise and clockwise in the upper, middle and bottom layers, respectively. The study also found that the three-layered rotating circulations are composed of the dynamically active ‘hotspots’ of intensified currents along the steep continental slope surrounding the deep basin, instead of an orderly structure in the entire region as previously conceived. Slope currents are mainly controlled by the combination effects of monsoon, Kuroshio intrusion, and the unique topography, and are constantly adjusted and regulated by the multiscale oceanic processes. The study demonstrated the three-dimensional structure and physical mechanism of the SCS circulation for the first time, and clarified previous misunderstanding of the water mass motion in this region. Based on these findings, Prof. Gan's team created the WavyOcean, a 3D simulation and visualization system for ocean circulation and biogeochemical processes in the SCS, which is validated and constrained by both observations and dynamics reasoning.
Prof. Gan said, "Because of failure in capturing the dynamic 'hotspot' in the marginal sea, almost all global models cannot accurately simulate the three-layer circulation structure and related physics in the South China Sea, even with the same spatial and temporal resolution. Therefore, compared with the open ocean, our understanding and simulation of the global marginal sea circulations, forced by multiple factors such as seafloor topography, water exchange through straits, and multi-scale dynamic processes, is more challenging than expected.”
"Observation is essential to ocean research. However, due to the strict spatial and temporal limitations of in-situ observations, it’s very difficult to understand the structure of ocean currents, especially for theoretical analysis of circulation dynamics. Numerical experiments or simulated 'observations' are crucial to ocean research, and an increasing amount of novel discoveries in ocean is now relying on numerical model that is rigorously validated by observations and geodynamic theory," he added. As an expert in computational geophysical fluid dynamics, Prof. Gan believes that numerical simulation is not a coding game of mere input and output, but rather a process of constructing an "exquisite" scientific numerical experiment and observation. In addition to simulating and forecasting the real ocean, numerical ocean modeling is a major scientific tool for understanding ocean processes and phenomena and assisting in exploring the unknowns.
The research results were recently published in Nature Communications by the team led by Prof. Gan, in collaboration with researchers from the University of Macau, and Southern University of Science and Technology. The research was co-funded by the CORE, the Hong Kong RGC and the National Natural Science Foundation of China. The CORE is jointly established by Qingdao National Science and Technology Laboratory and Hong Kong University of Science and Technology.
(This article was originally published on EurekAlert! on June 13, 2022)
A research team from the Hong Kong University of Science and Technology (HKUST) has demonstrated for the first time in-vivo imaging of fine neuronal structures in mouse cortex through the intact skull at an unprecedented depth of 750 µm below pia, making high-resolution microscopy in cortex near non-invasive and measurably facilitating the study of the living brain.
The direct and non-invasive visualization of neurons, glia, and microvasculature in the brain in vivo is critical for enhancing our understanding of how the brain functions. Over recent decades, great effort has been focused on developing novel techniques for in vivo imaging of the intact brain. However, none of the prevalent technologies, including ultrasound imaging (sonography), positron emission tomography (PET), and magnetic resonance imaging (MRI), provides sufficient spatial resolution to visualize biological structures at the subcellular level.
While optical microscopy such as three-photon microscopy (3PM) can provide structural and functional information in living specimens at high spatiotemporal resolution, optical aberration and scattering occur as light travels through and interacts with inhomogeneous biological tissues, fundamentally limiting the performance of optical microscopy in both resolution and depth.
Although adaptive optics (AO) is a possible solution to correct for the aberration and restore the resolution of in vivo optical microscopy, it is not without shortcomings: the guide star signal for the conventional wavefront sensing fades away quickly when imaging depth increases.
Now, co-led by Prof. QU Jianan, professor in Department of Electronic and Computer Engineering, and Prof. Nancy IP, chair professor in Division of Life Science, an HKUST research team developed a microscope that combines 3PM with two forms of AO, demonstrating fast measurements and the correction of both low-order and high-order aberrations in tissue at great depth.
The technology makes use of two AO techniques: direct focus sensing with phase-sensitive detection and conjugate adaptive optics (CAO) with remote focusing. The guide star signal is coded and then decoded in the aberration measurement to achieve AO correction of aberrations. These enable the accurate measurement of the aberrant electric-field point-spread function of a laser in tissue and the fast correction of the aberration over a large imaging volume in the brain.
The team validated the imaging performance of the AO-3PM system using a wavelength of 1300 nm, imaging through intact skull both in vivo and on in vitro preparations. The results showed that AO-3PM achieved high spatial resolution with a drastically improved fluorescence signal over a large depth, and high-resolution in vivo structural and functional imaging of mouse cortices through the intact skull up to 750 µm below the pia mater.
Further, by using a pupil AO-3PM, the team achieved high-resolution imaging of subcortical structures up to 1.1 mm below the pia mater within the intact brain. Taking advantage of the tight focus provided by their unique AO technique, the team went on to demonstrate the capability of AO-3PM to guide precise laser microsurgery and investigate post-operative microglial dynamics in the cortex through the intact skull.
“It is absolutely fun to exploit the marriage of electronics and optics to bring a new tool for experimental biology,” Prof. Qu said. “Overall, our results demonstrate that AO-3PM technology holds great potential to advance in vivo imaging techniques and facilitate study of living brain.”
“It is truly remarkable what this state-of-the-art AO-3PM system can achieve,” Prof. Ip explained, “the high performance and unparalleled accuracy of this advanced deep-brain imaging technology will substantially widen our understanding of living brain with optimal physiological representation.”
The research findings were recently published in Nature Biotechnology.
Bookcrossing has grown into a global phenomenon in the past decade, but the idea still hasn’t taken off in Hong Kong. A team of HKUST alumni are determined to build a local reading culture by releasing second-hand books into the wild, with the help of an app they designed.
Book circulation was stagnant with the traditional way of bookcrossing. Thousands of books ended up sitting on our shelves.
Danny CHEUNG (BSc Chem 2002) and Damon FAN (BBA Mark & MGTO 2003) established a bookcrossing club in Tsuen Wan in 2020 for book lovers to share used books, but responses were lukewarm. “We received thousands of books in the form of donations but only a few hundreds were picked up. But as we only had one location, it was difficult for us to give out these books efficiently. We were taking in too many books with too few ways to find takers for them! Simply put, the operation was not sustainable,” they say.
An automated bookcrossing kiosk
Determined to boost circulation, the duo co-founded Onepile with the idea of digitalizing the bookcrossing process, transforming the traditional book exchange practice into a sustainable social enterprise.
“I contacted a fellow HKUST graduate working in the software industry to write a web-based app which would allow donors and users to input and view information of the books online. The web-based app, combined with a customized book-vending machine, would then become an automated bookcrossing kiosk,” says Danny.
Users need to sign up for the app before they can donate or reserve a book. Donors can quickly upload information of their books simply by scanning their ISBN number in the back. All books are displayed on the app for users to reserve. After a reservation is made, a QR code will be sent to the user for picking up the book from the machine.
“If a book is not picked up within 48 hours, it will be released back to the pool to expedite circulation,” says Damon. The kiosk also provides quick UV sanitizing on books—fitting the needs of a hygiene-cautious crowd who loves to read.
The innovation has led Onepile to become one of the awardees of the Chan Dang Foundation Social Entrepreneurship Award in 2022—a new award launched at HKUST that encourages university members to turn business creative ideas into sustainable venture for promoting social good, with six project teams and startups each being awarded a grant.
More than 5,000 books were donated and picked up via the digital bookcrossing machine - the turnover is stella!
With confidence, Danny contacted the newly renovated Central Market, who quickly showed interest to deploy the kiosk at their premise.
“We’re happy to see the city’s very first digital bookcrossing kiosk landed in this prime location on the Hong Kong Island,” says Danny. “Turnover is stellar; the kiosk’s booking schedule is often full, and we have seen more than 5,000 books being donated and picked up since the kiosk was launched in February 2022. We were able to receive press, and now we also have enquiries from real estate developers, schools, shopping malls, and government departments.”
Their initial success has prompted more deployment of the book crossing kiosk across the city: a housing compound in Tsuen Wan, a primary school in Tin Shui Wai, HKUST The Base, and other planned locations underway.
“What Onepile is doing, while delivering on ESG Goals (Environmental, Social, and Governance”), is also a great example of STEM education and applications,” says Jessie LEE (BSc Chem 2002), one of the team members who comes from the STEM education sector. “We are organizing talks and coding classes in schools for the young. Our bookcrossing kiosk is an excellent example to teach students what IoT (Internet of Things) is about.”
A primary school eventually bought a bookcrossing machine from Onepile, and their students, with teachers’ help, has customized the proprietary program for the school environment.
While the bookcrossing service is free for general users, the team hopes the programming classes conducted in schools and the programming toolkit they are selling would contribute as a source of income for the Onepile project to sustain.
A green action
Onepile currently has 5,000 strong members, and the team expects the number to balloon to over 50,000 as deployment locations continue to grow.
The next challenge, for Danny, is to secure sufficient funding to scale up the business and deploy kiosk across the city realizing the potential opportunities.
“With corporations paying more attention to ESGs in today’s world, we are very excited to see enquiries growing on this essentially “green” concept of ours. We believe there is room for businesses like ours that promote green-living and book-loving in Hong Kong.”
Onepile helped me find a purpose in my second half of life.
For Damon in particular, what Onepile does is more than giving used books a second life. “Having established my career in the insurance profession, I’ve reached a point where I wish to make a bigger impact on the community. I’ve read a book about finding significance in midlife and now I’ve found mine – promoting a reading culture and preserving the planet – that’s what Onepile and the team is doing. If there are students who want to join and help , we welcome them to contact us anytime.”
“Onepile has brought together different generations of HKUST members. We have students and alumni from various disciplines and professions to create something that they believe is simple, yet meaningful, for the residents of Hong Kong—a platform to read, and share,” concludes Jessie.
Researchers at the Hong Kong Center for Neurodegenerative Diseases (HKCeND), founded by The Hong Kong University of Science and Technology (HKUST), have made promising breakthroughs in early diagnosis and therapeutic treatment of Alzheimer’s disease (AD) that have the potential to transform disease management. The team has established advanced biomarker discovery platforms, identified new blood-based biomarkers, and created an innovative artificial intelligence-based scoring system that enables risk prediction, early detection, and classification of AD. Furthermore, the team has successfully developed a gene therapy strategy as a novel therapeutic treatment for AD.
Established in 2020 with an initial funding of HK$500 million from the Hong Kong government’s InnoHK Clusters initiative, HKCeND aims to be the world’s leading research center focused on neurodegenerative diseases. A multi-disciplinary team of prominent scientists from HKUST, University College London and Stanford University School of Medicine are engaged in cutting-edge research with the goal of developing novel biomarkers and identifying therapeutic targets and systemic factors to treat neurodegenerative diseases.
AD, the most common form of dementia, is a devastating and incurable neurodegenerative disease that affects more than 50 million people globally. Treating AD remains a significant challenge since there are no objective diagnostic methods and patients are only diagnosed when the disease is at an advanced stage - after clinical symptoms such as memory loss appear. Given that disease onset is at least 10 - 20 years prior to the appearance of symptoms, early diagnosis of AD is the key to effective treatment. Early detection of AD, when it manifests as mild cognitive impairment or early dementia, would enable timely management/ therapeutic intervention resulting in improved outcomes. Biomarkers associated with early stages of AD have been found to have important applications in early diagnosis.
HKCeND researchers have extensive expertise in biomarker research. Previous achievements include conducting the first whole genome sequencing study of AD in the Chinese population and establishing the first comprehensive Chinese AD genetic database, resulting in the identification of AD genetic risk factors. These accomplishments have led to the development and establishment of novel and robust biomarker platforms at the HKCeND. Furthermore, by leveraging their genetic studies on Chinese AD patients and utilizing artificial intelligence tools, the team has developed the first deep learning-based polygenic risk scoring system that enables objective assessment of AD risk.
The team has also identified blood-based protein biomarkers and is developing a customized panel of AD blood protein biomarkers that can accurately classify patients with AD and evaluate disease status from a single drop of blood. This technology can be applied towards developing a clinical tool to efficiently and effectively diagnose AD at an early stage and for disease stratification. Given the clinical value of such tests, the team is actively pursuing commercialization opportunities with strategic industry partners. Collectively, these successes are increasing the HKCeND’s stature as the preeminent center for advanced biomarker research and laying a solid foundation for the development of precision diagnosis.
Concurrent to their biomarker research, the HKCeND team is also focusing on developing new therapeutic approaches for AD, in particular, gene therapy. Gene therapy has not been considered a promising therapeutic approach for brain diseases such as AD due to the lack of an effective and non-invasive delivery tool capable of crossing the blood-brain-barrier. Recently, the team generated the first engineered delivery vehicle and demonstrated its ability to not only effectively cross the blood-brain-barrier but also deliver a genome-editing tool to the entire brain through a single non-invasive intravenous administration. Using this system, the team successfully disrupted AD-associated mutations and alleviated AD pathologies in the entire brain of AD mouse models. This work is an important milestone in the development of new disease-modifying therapies.
“Together with our collaborators from different parts of the world, we are drawing leading scientists in the field to conduct pioneering research at the Center. The InnoHK initiative provides an important platform for the Center to facilitate multi-disciplinary and cross-institutional collaborations to further advance knowledge for early detection and therapeutic treatment of AD,” said Prof. Nancy Ip, Director of HKCeND and The Morningside Professor of Life Science at HKUST.
“We are confident that the Center will play a leading role in advancing research in neurodegenerative diseases, from talent development to conducting world-class research, to accelerate the development of precision diagnosis and medicine that will benefit millions of people globally,” Prof Ip added.
The research work of the Center is led by eminent scientists and brings together more than 60 researchers from all over the world. The Center is looking for research talent to join the fast-growing team, and is committed to nurturing a new generation of innovation and technology (I&T) talent.
(This article was originally published on EurekAlert! on May 7, 2022)
A research led by Hong Kong University of Science and Technology (HKUST) has revealed a novel mechanism that regulates secretion of sonic hedgehog (Shh), a key signaling molecular that plays an important role in cancer progression, in mammals, opening the door to novel therapeutic strategies for cancer induced by the hedgehog signaling pathway.
The hedgehog (Hh) signaling pathway is instrumental in regulating embryonic patterning and facilitating the development of the central nervous system and organs of the human body. Such a pathway transmitting information between cells is initiated by the Hh ligands, which are first secreted from the producing cells and then bound with specific receptors on target cells to induce Hh signaling (Fig. 1).
Hh signaling is a major target for cancer therapy because this pathway, when hijacked by cancer cells, can promote cancer progression. However, all of the current Hh antagonists function to inhibit the activity of major factors mediating Hh signaling in target cells, but do not effectively block cancer progression that is promoted by the secreted Hh ligands.
Now, an international research team led by Prof. GUO Yusong, Associate Professor of Division of Life Science at HKUST, has revealed the mechanism governing the secretion of sonic hedgehog, a key member of Hh ligands in mammals, from the producing cells, offering new insights into inhibiting its secretion and shutting down Hh signaling pathway when it is hijacked by cancer cells, thereby hindering cancer progression.
In the conventional secretory transport pathway, newly synthesized secretory proteins are firstly translocated into the endoplasmic reticulum (ER), where they are folded and modified. These proteins are then packaged into transport vesicles to be delivered to the Golgi apparatus to receive further modifications. Subsequently, they are enriched in transport vesicles at the trans Golgi network (TGN) and delivered to the plasma membrane to be secreted to the extracellular environment (Fig. 1).
To study the secretion of Shh, Prof. Guo’s team used a Retention Using Selective Hooks (RUSH) transport assay to analyze the secretion of sonic hedgehog in a synchronized manner (Video 1). Using this approach and other classical cellular and molecular biology approaches, the researchers elucidated that the secretion of Shh is regulated by the following steps:
- Cargo receptor SURF4 packages Shh into COPII vesicles by directly binding to the CW motif of Shh at the ER (Fig. 2, step 1).
- Upon reaching the Golgi, proteoglycans (PGs) compete with SURF4 to bind Shh and promote the dissociation of SURF4 and Shh (Fig. 2, step 2).
- The released SURF4 returns to the ER through COPI vesicles (Fig. 2, step 3).
- PGs promote TGN-to-cell surface transport of Shh (Fig. 2, step 4).
The research findings not only reveal a novel SURF4-to-proteoglycan relay mechanism that regulates the secretion of Shh, but also indicate that blocking the SURF4-Shh interaction is an effective way to inhibit Shh secretion.
Prof. Guo said, “This presents the possibility of developing novel therapeutic strategies to block cancer progression, especially ligand-dependent cancer progression, induced by Hh signaling pathway.”
The results were recently published in Proceedings of the National Academy of Sciences (PNAS), with an US provisional patent already submitted by the research team for consideration.
Prof. Guo is the corresponding author of the paper, while Prof. Elizabeth A. MILLER from MRC Laboratory of Molecular Biology, Prof. YAO Shuhuai and Prof. HUANG Jinqing from HKUST, Prof. ZHANG Liang from City University of Hong Kong, and Prof. HU Junjie from Chinese Academy of Sciences also participated in this study. Dr. TANG Xiao from HKUST is the first author of this study.