Division of Life Science (LIFS) Research Teams Win Gold+ Awards at the 51st Geneva Inventions Expo

Gold Medal with Congratulations of the Jury (Gold+):

1. Next-Generation Portable Recombinant Antivenom for Snakebites Envenoming

   Principal Investigators: Prof. ZHU Guang, (Professor, Division of Life Science, and Department of Chemical and Biological Engineering); Dr. XU Naining, (Post-doctoral Fellow, LIFS)

   The Challenge: According to the World Health Organization (WHO), an estimated 5.4 million people are bitten by snakes annually, resulting in many cases of envenoming. This leads to approximately 81,000 to 138,000 deaths each year. In Hong Kong, the Poison Control Centre reported nearly 300 snakebite‑related hospital admissions between 2021 and 2023. Traditional antivenom production involves injecting snake venom into large animals, such as horses or sheep, to stimulate antibody production. The antibodies are then extracted, a costly process that may cause allergic reactions in some individuals.

   The Innovation: The team’s next‑generation recombinant antivenom utilizes human monoclonal antibody cocktails developed through a single B-cell screening platform to significantly reduce allergic responses. Lightweight and easy to use, this autoinjector enables immediate on‑site use with a single press to save critical time during emergencies.

2. EpiLumenix: Ultra‑Early Blood Screening Platform to Prevent Cancer before its Onset

   Principal Investigator: Prof. ZHANG Li-Sheng, (Assistant Professor, Division of Life Science and Department of Chemistry) with CHAN Hei-Man and TSE Man–Hin (MPhil students, LIFS).

   The Challenge: Colorectal cancer is the second leading cause of cancer deaths in Hong Kong, with a five‑year survival rate of only about 9.3% for late‑stage cases. However, colonoscopy, the clinical gold standard, is invasive, leading to low participation rates. In addition, stool‑based tests and blood‑derived cell-free DNA assays often lack the necessary sensitivity to detect precancerous lesions and Stage 0 cancers, which can delay diagnoses that could have been prevented.

   The Innovation: The team has developed a novel blood screening platform, EpiLumenix, which integrates cell‑free RNA epitranscriptomics and AI to capture dynamic tumor microenvironment fingerprints from just 2 mL of blood. This platform achieves a groundbreaking 75% sensitivity for Stage 0 colorectal cancer and advanced adenomas, significantly outperforming current commercial stool and cfDNA tests. As a less‑invasive solution, it requires no fasting or bowel preparation, thereby improving patient compliance, and shifting colorectal cancer management from passive treatment to proactive, precision-based early detection and prevention.

Gold Medal:

Targeting C9orf72 G-Quadruplexes: Structure-Based and AI-Optimized Small Molecule Therapeutics for ALS/FTD

Principal Investigators: Prof. ZHU Guang, (Professor, LIFS, and CBE); Dr. XU Naining, (Post-doctoral Fellow, LIFS)

The Challenge: Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the progressive loss of motor neurons. Patients face a devastating prognosis, with a median survival of only 2 to 5 years following diagnosis, and no curative therapies currently available. A major genetic contributor to ALS is the C9orf72 mutation, which involves extensive G4C2 DNA/RNA repeat expansions that form toxic aggregates and drive neuronal dysfunction. As the global incidence of ALS increases with an aging population, existing FDA approved treatments remain largely symptomatic and fail to address this underlying genetic pathology. Consequently, there is a critical unmet medical need for a true disease modifying therapy that targets the root cause of ALS.

The Innovation: Led by Prof. ZHU Guang at HKUST, the research team developed GY 368, a first in class small molecule therapy that directly targets the C9orf72 gene mutation. Using an AI driven targeted drug discovery platform, the team optimized GY 368 to selectively resolve pathogenic G quadruplex structures. In preclinical models, GY 368 demonstrated robust blood–brain barrier penetration, significantly reduced toxic RNA foci, and improved motor function without observable toxicity. By addressing a fundamental genetic cause of ALS and frontotemporal dementia (FTD), this breakthrough therapy offers new promise for extending patient survival.

Driving Global Impact

These achievements underscore HKUST’s commitment to translational research, bridging the gap between laboratory discovery and real-world industrial application to improve global healthcare outcomes and drive innovation in the biotechnology sector.

For further information please visit: HKUST News-Geneva Inventions Expo

LIFS Alumni Homecoming 2026 – Event Highlights

More than 90 alumni from the Division returned to campus on 14 March 2026 to reconnect with fellow graduates and professors at the LIFS Alumni Homecoming 2026.

The event started with a welcoming cocktail reception followed by a buffet lunch. Prof. Guojun BU, Head of Division, shared recent developments and achievements of LIFS, while Prof. Yung Hou WONG, Dean of Science, provided updates on the progress and future plans of HKUST’s Medical School.

Representatives from the Life Science Alumni Association (LSAA) introduced their activities and upcoming plans. Two new initiatives from the Development & Alumni Office (DAO) – Alumni Commons and the Class Ambassador Program – were also presented.  Faculty members then led a celebratory toast before group photos were taken.

In the afternoon, alumni visited the newly launched Alumni Commons, designed to enhance alumni engagement and community building.

The gathering served as a meaningful opportunity for alumni and faculty to reconnect, build new ties, and stay updated with the Division’s latest developments. LIFS looks forward to continuing such reunions to strengthen alumni bonds and foster a lasting sense of belonging.

Repost from: https://alum.hkust.edu.hk/events/lifs-alumni-homecoming-2026

HKUST Researchers Achieve Breakthrough in RNA Silencing Mechanism

The message of human life is encoded in our genomic DNA through transcription of messenger RNAs which carries and executes the genetic instructions. RNA molecules, typically single-stranded and composed of ribonucleotides (A, U, G, and C), play essential cellular roles ranging from protein synthesis and gene regulation to serving as genetic material in certain viruses. Within this RNA-based regulatory landscape, the enzyme DICER functions as a highly precise “molecular scissors.” It cleaves double-stranded RNA precursors into short regulatory RNAs that are subsequently incorporated into the RNA-induced silencing complex (RISC), enabling the cell to identify and suppress incorrect or unnecessary genetic messages—much like marking and deleting errors in a text. 

For years, researchers have sought to understand how DICER achieves its extraordinary cleavage accuracy. Using state-of-the-art biochemical and structural biology techniques and high-resolution cryoelectron microscopy (cryo-EM), the HKUST research team visualized DICER–RNA interactions at an atomic level. The study’s first author Minh Khoa Ngo explained, “CryoEM allowed us to observe how RNA substrates engage with DICER at an atomic detail. These structural snapshots vividly reveal the dynamic adjustments DICER makes when processing different RNA sequences, fundamentally reshaping our understanding of how this enzyme functions.”

The team discovered that before cleavage occurs, DICER undergoes conformational adjustments that guide RNA substrates into the correct register. The enzyme then uses specific structural elements—particularly amino acids within 5′-end binding pockets—to align the RNA precisely before adopting the “cleavage ready” conformation. 

This diagram shows DICER’s Decision Process, illustrating how the enzyme acts like a “smart ruler” to decide exactly where to snip the RNA strand. The “G” Path (Left): When RNA starts with the letter G, it fits into a green pocket. Normally, this leads to a shorter cut (21 units). However, if the RNA has a specific internal feature, the enzyme physically twists the strand (red lines), overriding the rule to make a longer cut (22 units). The “U” Path (Right): When RNA starts with the letter U, it fits into a pink pocket. This pocket is shaped to naturally align the RNA for the longer cut (22 units) every time, regardless of its internal feature.

Prof. Nguyen, the corresponding author, elaborated: “It is as if the scissors can ‘read’ exactly where the RNA should be cut at single nucleotide resolution, ensuring the integrity of the entire message. Our study uncovers not only the previously known U-favoured 5′-end binding pocket, but also a newly identified G-favoured 5′-end binding pocket. Together, these form a dual-pocket mechanism that determines cleavage positioning, providing an entirely new framework for understanding how DICER accommodates and processes diverse RNA substrates.”

He further added: “The importance of this discovery extends beyond basic biology. By revealing how DICER integrates 5′-end identity, RNA motifs, and domain motions to maintain cleavage fidelity, our findings lay a mechanistic foundation for improving RNA-based therapeutics, optimizing gene silencing technologies, and uncovering the molecular origins of DICER-related genetic diseases.”

Repost from

https://hkust.edu.hk/news/hkust-researchers-achieve-breakthrough-rna-silencing-mechanism

LIFS Summer Recruitment Camp 2026 (6 July – 10 July 2026)

LIFS Summer Research Program 2026 (2 July – 6 August 2026)

HKUST researchers have developed CRACI to pinpoint dihydrouridine, an abundant RNA modification

A team led by Prof. ZHANG Li‑Sheng (Division of Life Science & Department of Chemistry, HKUST) has developed Chemical Reduction Assisted Cytosine Incorporation sequencing (CRACI) — a sensitive method that quantitatively pinpoints dihydrouridine (D),  the most abundant tRNA modification at the single-base resolution.

Small chemical marks on RNA—like D—can work like fine‑tuning structural switches, influencing how genes are expressed. Until now, these D marks were hard to detect. With CRACI, the team created the first detailed maps of D in cellular tRNAs from mammals and plants, including those inside mitochondria.

Key discoveries:

• Developed CRACI as the first method to enable whole-transcriptome quantitative mapping of D marks at base resolution.
• Identified DUS2L, a protein that writes D marks in human mitochondrial tRNAs.
• Found that D20a strongly regulate tRNA stability, which can even affect the nearby D installation.
• Showed that D marks in human mRNA are present but very rare and occur at very low levels.

Because D is common and conserved across species, and related enzymes are potentially linked to human disease, CRACI gives researchers a powerful platform to explore how these RNA marks shape cell function, stress responses, and health. The team plans to extend CRACI to primary cells and tissues to build a clear and comprehensive picture of D roles in disease contexts.

Journal reference

Ju, CW., Li, H., Jiang, B. et al. Quantitative CRACI reveals transcriptome-wide distribution of RNA dihydrouridine at base resolution. Nat Commun 16, 8863 (2025). https://doi.org/10.1038/s41467-025-63918-w

Professor ZHAI Yuanliang receives 2025/26 RGC CRF Collaborative Research Project Grant

Prof. ZHAI Yuanliang,  Associate Professor in the Division of Life Science (LIFS), has been awarded the Collaborative Research Project Grant (CRPG) under the Collaborative Research Fund (CRF) 2025/26. He was awarded HKD7.96 million for the project “Molecular Mechanisms of Replisome Coupling” in collaboration with The University of Hong Kong (HKU).

HKUST Team Develops a Novel Vesicle-Based Method Advancing Membrane Protein Research

 Membrane proteins are crucial for numerous biological processes and serve as important drug targets. For decades, scientists have relied on detergents to extract membrane proteins from cell membranes for structural studies. While detergent-based approaches have significantly advanced our understanding of membrane protein structures, they present certain limitations, such as resource-intensive detergent screening and the absence of native membrane lipids, which can hinder investigations into lipid-mediated regulation. To address these challenges, a research team led by Prof. DANG Shangyu from the Division of Life Science at the Hong Kong University of Science and Technology (HKUST) has developed a novel vesicle-based method that preserves the native lipid environment of membrane proteins, which can advance structural and functional studies.

After four years of systematic investigation, Prof. Dang’s team bypassed the need for purification with detergents by directly generating vesicles containing the target protein from cell membranes. This approach produced samples suitable for cryo-EM imaging and structural studies. The team established a comprehensive workflow for the preparation, purification, and quality control of vesicle samples, making this method applicable to various membrane systems. To address the strong background signal and interference caused by the native membrane structure, they developed a micrograph-based sorting approach integrated with an artificial intelligence model to specifically isolate high-quality membrane protein particles. They successfully applied this method to multiple membrane protein systems, resolving the structure of the overexpressed AcrB protein in E. coli cell membranes at 3.9 Å resolution and the structure of the native respiratory chain complex III in porcine heart mitochondrial inner membranes at 3.0 Å resolution.

A scientific picture of Cryo-EM structure determination of AcrB in vesicle.

LIU Hang, a Ph.D. candidate from Prof. Dang’s team and the first author of the study, reflected: “Leveraging Prof. Dang’s multidisciplinary approach, our team has successfully developed a comprehensive system for in-situ structural studies of membrane proteins, encompassing both sample preparation and data processing, which overcomes challenges that were previously insurmountable. “

Compared to traditional detergent-based methods, this novel approach offers key advantages, including lower cost, simpler operation, and greater ease of use. Crucially, it preserves the native membrane environment and key lipid molecules, maintaining the protein’s natural conformation to the greatest extent possible. The method also demonstrates versatility, making it applicable to different membrane proteins across various species and cellular membrane structures. It promises to significantly reduce the workload for researchers, simplify the determination of membrane protein structures, and broaden the scope of cryo-EM structural biology.

“This vesicle-based platform preserves physiological lipid environments while eliminating the burdens of detergent screening,” explained Prof. Dang. “It provides an opportunity to study membrane proteins in their native environments. With further optimization, we aim to achieve structural proteomics of membrane proteins in specific biological membrane systems, such as mitochondria, under various physiological and pathological conditions, offering valuable insights into diseases.”

This research was published in the Proceedings of the National Academy of Sciences (PNAS). Prof. DANG Shangyu is the corresponding author, Ph.D. candidate LIU Hang is the first author, and undergraduate student TSE Chun Mong is the second author.

Repost from

https://science.hkust.edu.hk/news/hkust-team-develops-novel-vesicle-based-method-advancing-membrane-protein-research

HKUST Researchers Use Vesicle Proteomics to Reveal Novel Cargo Clients and Accessory Factors for AP-1 and AP-4

The secretory pathway in eukaryotic cells is crucial for maintaining cellular function and physiological activities, as it ensures the accurate transport of proteins to specific subcellular locations or for secretion outside the cell. A research team led by Prof. GUO Yusong from the Division of Life Science at the Hong Kong University of Science and Technology (HKUST) has been extensively investigating the molecular mechanisms by which cargo proteins are recognized and loaded into transport vesicles in the secretory pathway. The team has successfully reconstituted the packaging of multiple disease-related cargo proteins into vesicles along the secretory route, providing a powerful tool for dissecting the molecular mechanisms of cargo loading. In addition, they developed an innovative analysis platform that integrates vesicle reconstitution with electron microscopy and proteomics, enabling systematic identification of vesicle protein composition and morphological features. This comprehensive approach has proven effective in uncovering novel cargo clients and cellular factors that mediate vesicular trafficking (Figure 1).

Figure 1: Schematic of the research approach based on vesicle reconstitution combined with electron microscopy and proteomics. (References: PNAS 2019, PNAS 2021, PNAS 2025, Nature Plants 2021)

The research team led by Prof. Guo, in collaboration with Prof. YAO Zhong-Ping’s team at The Hong Kong Polytechnic University (PolyU), published their findings in PNAS. This study integrates in vitro vesicle reconstitution with quantitative mass spectrometry to systematically identify transport cargos mediated by the adaptor protein complexes AP-1 and AP-4. It also elucidates key cytosolic regulatory factors involved in AP-4–mediated vesicle trafficking.

Within the secretory pathway, the trans-Golgi network (TGN) serves as a central sorting hub, packaging proteins precisely into transport vesicles. Sorting errors can prevent cargos from reaching their correct targets, leading to defects in cell polarity, immune function, and other physiological processes. Key factors involved in protein sorting at the TGN are adaptor protein (AP) complexes, AP-1 and AP-4. Mutations in their genes are closely linked to several human diseases: AP1S1 mutations (encoding the σ1 subunit of AP-1) are associated with MEDNIK syndrome; AP1S2 mutations can cause X-linked intellectual disability; and mutations in any AP-4 subunit lead to “AP-4 deficiency syndrome,” a complex hereditary spastic paraplegia. Therefore, defining the cargo clients of AP-1 and AP-4 is crucial for understanding their physiological and pathological roles. However, the full repertoire of cargos and cofactors they mediate remains unclear. Notably, AP-4–mediated TGN export appears to be clathrin-independent, suggesting that vesicle formation may depend on yet-unidentified accessory factors.

In this study, Prof. Guo’s team performed vesicle formation assays using AP1γ1 or AP4ε knockout cells, isolated vesicle fractions, and conducted proteome-wide analysis by quantitative mass spectrometry. This approach allowed them to identify AP-1– and AP-4–dependent cargo proteins exported from the TGN, as well as key cytosolic accessory factors required for AP-4–mediated transport. Subsequent biochemical validation revealed that CAB45 is an AP-1–dependent cargo, while ATRAP (an angiotensin II type I receptor–associated protein) is an AP-4–dependent cargo. Notably, AP-4 recognizes a tyrosine-based motif at the cytosolic terminus of ATRAP to mediate its loading into transport vesicles from the Golgi.

The study also found that the cytosolic proteins WDR44 and PRRC1 play critical roles in AP-4–mediated cargo sorting. When WDR44 levels were knocked down, the AP-4 cargo ATG9A abnormally accumulated at the Golgi. Similarly, PRRC1 knockout caused ATG9A to be retained in the endoplasmic reticulum, impairing cellular autophagy.  Another AP-4 cargo, ATRAP, also accumulated in the Golgi under these conditions. “These results not only deepen our understanding of AP-1 and AP-4 functions in secretory trafficking but also provide a powerful methodological toolkit for systematically dissecting the mechanisms of specific accessory factors,” said Prof. Guo.

The study’s co-corresponding authors are Prof. Guo of HKUST and Prof. Yao of PolyU. Dr. PENG Ziqing, a postdoctoral researcher at HKUST, is the first author.

Repost from

https://science.hkust.edu.hk/news/hkust-researchers-use-vesicle-proteomics-reveal-novel-cargo-clients-and-accessory-factors-ap-1

HKUST Scientists Reveal Critical Impacts of a Chinese Genetic Risk Factor in Alzheimer’s Disease

AD currently affects approximately 10 million people in Chinese Mainland, with the number projected to rise to around 50 million by 2050. Genetic factors account for 60-80% of the risk for late-onset AD, with the APOE gene being the most extensively studied, followed by TREM2. Both genetic risk factors exhibit significant differences in prevalence and risk effects across different ethnic populations. In particular, the most studied TREM2 genetic variant, R47H, is enriched in European populations but not found in Chinese populations. As most AD genetic studies have been conducted in European populations, it is crucial to undertake such studies on diverse populations.

To address this gap, the Hong Kong Center for Neurodegenerative Diseases (HKCeND) launched its Biobank (HKCeND Biobank) for AD research. Led by HKUST and in collaboration with hospitals in Hong Kong, this biobank collects and consolidates comprehensive clinical, neuroimaging, and multi-omics data from individuals of ethnic Chinese origin. This makes it a critical resource for investigating Chinese-enriched genetic factors such as the TREM2 H157Y variant.

This research on the genetic variant was conducted by a team led by Prof. Nancy IP, President and the Morningside Professor of Life Science at HKUST. She is also the Director of the State Key Laboratory of Nervous System Disorders (SKLNSD) at HKUST and the Center Director of the InnoHK HKCeND.

The study resulted in several novel findings. The clinical case study showed that TREM2 H157Y variant carriers with the APOE-ε4 risk factor exhibit more rapid clinical progression in the early stages of the disease, compared to non-carriers. Cognitive assessments, neuroimaging, and AD blood biomarker analyses indicated that AD patients carrying the TREM2 H157Y variant experience significantly worsened cognitive functions, more severe neurodegeneration, and more severe AD pathology. Additionally, blood protein profile analysis revealed alterations in immune, vascular, and bone-related biological processes in these individuals. This highlights the use of blood biomarkers to investigate how genetic risk factors influence AD pathology, generating new insights into AD biology and novel therapeutic development.

Prof. Ip remarked, “This study is the first to demonstrate that the TREM2 H157Y genetic variant is associated with more severe AD pathology and neurodegeneration. The prevalence of the TREM2 H157Y variant among ethnic Chinese individuals emphasizes the importance of conducting genetic studies in the Chinese population.” She added, “This study also highlights the critical clinical implications of the genetic variant for timely intervention and personalized disease management. Our research benefits from public participation and close collaboration between clinicians and scientists, effectively linking scientific findings to improved patient outcomes.”

The study was supported by multiple funding bodies, including the InnoHK initiative of the Innovation and Technology Commission (ITC) of the Hong Kong Special Administrative Region Government, the Areas of Excellence Scheme of the University Grants Committee, the Research Grants Council (RGC) of Hong Kong, the ITC Grant, the Chow Tai Fook Charity Foundation, the National Natural Science Foundation of China (NSFC)/RGC Joint Research Scheme, and the SIAT-HKUST Joint Laboratory for Brain Science, under the Chinese Academy of Sciences. The clinical case study was conducted in collaboration with Prof. Timothy Kwok from the Prince of Wales Hospital, The Chinese University of Hong Kong.

Repost from

https://hkust.edu.hk/news/hkust-scientists-reveal-critical-impacts-chinese-genetic-risk-factor-alzheimers-disease