Prof. Tom CHEUNG, Associate Head (Research and Development), Division of Life Science
Project title: Post-transcriptional regulation of muscle stem cell quiescence during physiological conditions and aging
Amount of Fellowship Grant: ~HKD 5.3 million
Abstract
With better healthcare and living conditions, humans are living longer, but aging is accompanied by poorer health span partly due to the aging-related deterioration in tissue functions. Muscle stem cells (MuSCs) are the adult stem cells of skeletal muscle, playing critical roles in maintaining tissue homeostasis and repair. MuSCs remain in a dormant state until they receive signals from external stimuli (e.g. muscle injury) to rapidly activate, proliferate, and differentiate to regenerate the injured muscle. However, this regenerative capacity is lost during aging, leading to loss of muscle mass, function, and capacity for repair. MuSC functions are under tight regulatory control through numerous pathways, which become dysregulated during aging. The Cheung laboratory is dedicated to understanding why MuSC functions are lost and developing interventions to restore their stem cell functions. This project will investigate how these mechanisms regulate MuSC functions and how aging may impact these pathways.
Prof. LIU Kai, Professor, Division of Life Science
Project title: Enhance locomotor recovery by transforming a complete spinal cord injury into an incomplete injury
Amount of Fellowship Grant: ~HKD 5.3 million
Abstract
Severe and long-lasting neurological deficits result from neurological injuries such as brain or spinal cord injury. Successful regeneration and reconnection of nerves has the potential to restore lost function. The team’s previous work on optic nerve injury and regeneration has led to a new approach to promote axonal regeneration and neurological recovery. They will apply this knowledge and methods to spinal cord injury. Recent research on spinal cord injury has shown that multiple descending tracts can regenerate across the lesion site, offering exciting opportunities to study the function of axonal pathways in the regeneration and repair of damaged neural circuits. The team aims to enhance functional recovery by combining various strategies and gain a deeper understanding of the cellular and molecular mechanisms involved in nerve fiber regeneration and functional connectivity. Successful completion of this project will improve our understanding of the fundamental processes that promote functional connectivity after central nervous system injury.
HKUST President Prof. Nancy IP said, “This marks another significant accomplishment of the University, shortly after we yielded impressive results in RGC’s Areas of Excellence and Theme-based Research Schemes. At HKUST, we are committed to attracting and nurturing top-tier research talents who are dedicated to making a pivotal impact on addressing global challenges.
HKUST Vice-President for Research and Development Prof. Tim CHENG also expressed delight at the faculty’s achievements. He said, “Thanks to these additional research funding and support from RGC, our faculty members can dedicate more time to their foundational research and nurturing the next generation of research talent. This is essential for the University to further our goal of making HKUST a powerhouse of innovation and achievement.”
The annual RFS and SRFS aim to provide continuous research support integrated with relief from teaching and administrative duties for a 5-year period to 10 outstanding mid-career researchers at the Associate Professor rank and 10 senior researchers at the full Professor rank at UGC-funded universities in Hong Kong. This initiative is designed to enable academics to focus on research and development, as well as the time and resources necessary to nurture the next generation of local research talents for Hong Kong.
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A research team from the Division of Life Science, (HKUST), led by Mr. Shihan ZHU (PhD student) and Dr. Zeyu Shen (post-doctoral researcher), with the guidance of Prof. ZHANG Mingjie, former Chair Professor in Life Science at HKUST have recently published a paper in the prestigious journal Science.In this study, the researchers wanted to understand how excitatory and inhibitory neuronal synapses, especially the post-synaptic densities (ePSDs and iPSDs, respectively), inside living cells stay separate from each other. These synapses are like small compartments within cells and are crucial for communication between brain cells.
They used biochemical reconstitutions in vitro and in cells and found that these PSDs form distinct groups of molecules through a process called phase separation, similar to how oil and water separate into layers. The molecules within the excitatory postsynapse group stick together, as do the molecules within the inhibitory postsynapse group. Importantly, these groups do not mix with each other.
What’s particularly intriguing is that the researchers attempted to mix the molecules from the two synapse groups but were unable to do so. This suggests that the molecules naturally have a tendency to remain separate while undergoing phase separation. This finding indicates that the separation of molecules within these synapses is a normal process that occurs naturally.
Understanding how these synapses stay separate is important because it helps us understand the function of the brain. Maintaining a balance between excitatory and inhibitory signals is crucial for proper brain function. If these signals were to mix, it could disrupt the normal operation of brain cells.
This research also has broader implications for understanding how different structures within cells can remain separate. Many structures in cells lack surrounding membranes, yet they manage to maintain their distinct compartments. By studying these synapses, scientists have uncovered a fundamental principle that can aid our understanding of how other structures in cells remain separate.
This study deepens our understanding of the brain and may potentially contribute to the development of new strategies for targeting specific molecules or networks within cells for medical purposes.
Publication Reference:
Zhu S, Shen Z, Wu X, Han W, Jia B, Lu W, Zhang M. Demixing is a default process for biological condensates formed via phase separation. Science 384(6698):920-928. (2024) https://doi.org/10.1126/science.adj7066.
Many congratulations to Prof. David Karl Banfield, Professor of Life Science, for being awarded the School Service Award for his remarkable contributions to the Division of Life Science in various initiatives including the Open Lab Project, the undergraduate program curriculum, and his contributions to the university in different roles.
The Annual School of Science Awards were established in 1996/97 to recognize faculty members and teaching-track faculty for their outstanding achievements in teaching, research, or service. This year, the awards were presented by Prof. Yung Hou Wong, the Dean of Science, during the School Board Meeting on May 14, 2024.
In a groundbreaking study conducted by PhD student Hua QIU and post-doctoral researcher Dr. Xiandeng WU, from the Division of Life Science led by Prof. Mingjie Zhang (formerly from the Division of Life Science at HKUST), significant progress has been made in understanding the mechanisms involved in short-distance, directional transport of vesicles within cells. Vesicles are small sac-like structures responsible for transporting crucial molecules within cells. While the involvement of molecular motors in long-distance vesicle transport is known, the mechanisms governing shorter distances have remained unclear. In this study, the team specifically investigated synaptic vesicles, which play a vital role in transmitting signals between nerve cells.
The research team discovered that a process known as phase separation, where certain proteins form distinct condensed structures, plays a crucial role in facilitating regulated and directional vesicle transport. More specifically, a large scaffold protein called Piccolo undergoes phase separation with synaptic vesicles in response to calcium signals. This enables Piccolo to extract the vesicles from a clustered reservoir and deposit them onto another condensed structure called the active zone. Consequently, this process allows for the transport of synaptic vesicles between different sub-compartments within nerve cell terminals. The team also identified another protein called TFG that participates in vesicle trafficking between cellular compartments through phase separation.
These findings have significant implications as they unveil a previously unknown mechanism for short-distance, directional vesicle transport in cells. While long-distance transport relies on molecular motors, this research highlights the active role of protein phase separation in facilitating vesicle movement over shorter distances. Understanding these mechanisms is crucial for deciphering how cells precisely control the distribution of vesicles within subcellular compartments. Moreover, this knowledge expands our understanding of cellular processes and may have implications for various biological functions that rely on vesicle transport, including neuronal communication and secretion of molecules in other cell types. Ultimately, these findings open up new avenues for further research and potential applications in the medical field.
Publication Reference:
Hua Qiu, Xiandeng Wu, Xiaoli Ma, Shulin Li, Qixu Cai, Marcelo Ganzella, Liang Ge, Hong Zhang, and Mingjie Zhang. Short-distance vesicle transport via phase separation, Cell 187, 1–19 (2024), https://doi.org/10.1016/j.cell.2024.03.003.
About 60 alumni from the Division of Life Science (LIFS) and the former Department of Biochemistry / Department of Biology ‒ BSc Biochemistry (BICH), BSc Biology (BIOL), BSc Biochemistry & Cell Biology (BCB), BSc Biological Science (BISC), BSc Biotechnology (BIOT), and BSc Biotechnology & Business (BIBU) ‒ returned to the campus on Saturday 16th March 2024 to catch up with old friends, meet new ones, reconnect with professors, and learn about the latest developments at the Division.
There was a cocktail reception before the buffet lunch. To kick off the lunch, Prof. Robert KO (Acting Division Head) and Prof. Yung Hou WONG (Dean of Science and Chair Professor of LIFS) delivered their welcome messages, followed by a toasting from the LIFS faculty members. Mr. Michael CHOW (President of the Life Science Alumni Association, LSAA) also gave a brief note on LSAA and shared their past alumni events.
The Homecoming was a happy reunion for all and received very positive feedback. Many alumni expressed their interest in attending forthcoming get-togethers.
It was wonderful to see our alumni again since the last reunion in 2019 and that they feel a strong connection to the Division. We look forward to building stronger ties with our alumni and collaborating with them along our journey of excellence!
A joint study led by HKUST, HKU, and other institutions has been selected as one of the Top 10 Scientific Advances in China for 2023, making it the only research project from Hong Kong to be included in the list.
The study, focused on DNA replication initiation, unveiled a new mechanism in the regulation of DNA replication and was led by Prof. ZHAI Yuanliang from HKU School of Biological Sciences, Prof. DANG Shangyu from HKUST Division of Life Science (LIFS), and Prof. TYE Bik-Kwoon from HKUST Institute for Advanced Study (IAS). The team’s groundbreaking discovery of the human pre-replication complex (Pre-RC) and its atomic resolution structure provides crucial insights for developing innovative anticancer strategies that can selectively target cancer cells. The recognition received highlights the respect and esteem their work holds within the scientific community. Prof. ZHAI expressed the significance of the research in deepening our understanding of DNA replication and its potential implications in diseases like cancer. Prof. DANG emphasized the importance of their research breakthrough in enhancing the specificity of chemotherapy drugs and expressed gratitude for the support provided by the Lo Kwee Seong (LKS) Foundation in establishing the HKUST Biological Cryo-EM Center, which facilitated numerous breakthroughs in their research. The team looks forward to further advancements and hopes for new possibilities in cancer treatment.
Journal Reference:
Li, J., Dong, J., Wang, W., Yu, D., Fan, X., Hui, Y. C., Lee, C. S. K., Lam, W. H., Alary, N., Yang, Y., Zhang, Y., Zhao, Q., Chen, C., Tye, B.-K., Dang, S., Zhai, Y. The human pre-replication complex is an open complex. Cell 2023 Jan 5, 186 (1): 98-111.e21. doi.org/10.1016/j.cell.2022.12.008
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An international research collaboration led by Professor Nancy IP, has made a significant breakthrough in Alzheimer’s disease (AD) diagnosis and management. The team has developed a cutting-edge blood test for the early detection of AD and mild cognitive impairment (MCI) with remarkable accuracy rates of over 96% and 87% respectively. This blood test is applicable across diverse ethnic populations, providing a global solution to the diagnosis and management of AD.
AD is a neurodegenerative disease that affects over 50 million people worldwide. The accumulation of toxic amyloid beta (Aβ) in the brain is a major hallmark of the disease, leading to the loss of brain cells and cognitive decline. The recently approved AD drug Lecanemab targets elevated Aβ in the brain, offering new hope for treatment. However, the majority of individuals with AD and MCI go undiagnosed and untreated due to the challenges of early diagnosis. Currently, elevated Aβ can only be measured through costly brain imaging or invasive procedures, and symptoms typically appear late in the disease’s progression.
The HKUST-led research team has developed a simple blood test that accurately identifies individuals with MCI and mild AD, while also detecting elevated Aβ in the brain. The test measures the levels of 21 proteins in multiple biological pathways, providing a comprehensive profile of AD for each individual. This allows for more accurate classification of AD and MCI, as well as close monitoring of disease progression. The test has demonstrated robust performance in distinguishing individuals with AD and MCI from cognitively normal people in a multinational study involving individuals of Chinese and European descent.
The HKUST blood test represents a significant advancement in AD diagnosis and precision treatment. It offers a less invasive and more effective diagnostic method and has the potential to revolutionize the field of AD management. The test can also be used to screen individuals for suitable drug treatments in clinical studies and monitor disease progression and drug responses. Additionally, it may facilitate the development of personalized treatments by uncovering the molecular underpinnings of AD that vary between individuals and ethnicities.
The research collaboration involved University College London and the Barcelona βeta Brain Research Center, as well as clinicians from local and overseas hospitals.
The findings have been published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, and the technology has been licensed to a start-up company of HKUST, Cognitact Limited, to provide testing services to the public.
Journal Reference:
Jiang Y, Zhou X, Ip FC, Chan P, Chen Y, Lai NCH, Cheung K, Lo RMN, Tong EPS, Wong BWY, Chan ALT, Mok VCT, Kwok TCY, Mok KY, Hardy J, Zetterberg H, Fu AKY, Ip NY. Large-scale plasma proteomic profiling identifies a high-performance biomarker panel for Alzheimer’s disease screening and staging. Alzheimers Dement. 2022 Jan;18(1):88-102. doi: 10.1002/alz.12369.
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LIFS Summer Recruitment Camp 2024 for 2025/26 Fall Postgraduate Admission: 8 July 2024 – 12 July 2024 (5 days)
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A study led by Professor Shanyu Dang and his research team at HKUST is shedding light on TMEM63 proteins. These proteins are calcium-permeable channels in animals that are primarily activated by hypo-osmolality, and they play crucial roles in various physiological functions. Deficiencies in these channels have been associated with several diseases, including hearing loss. However, their structures and physiological roles have remained elusive until now.
To investigate these proteins, the team utilized cryo-electron microscopy (cryo-EM) to examine the structure of TMEM63C in mouse and compared it to other TMEM63 proteins as well as their plant orthologues known as OSCAs. Notably, they discovered significant differences in structure among these proteins.
Furthermore, the researchers conducted experiments to understand the functioning of TMEM63 proteins. They identified specific regions of the protein that are essential for its activity and elucidated the critical roles of the coupling between TM0 and TM6 in channel activity. Additionally, they observed that TMEM63C acts as a single unit, while TMEM63B can exist as both a single unit and a pair. This suggests that TMEM63 proteins can regulate their function through their dimerization.
Understanding TMEM63 proteins is crucial because they are involved in how cells perceive and respond to mechanical forces. These forces are vital for cellular adaptation and survival in their environment.
The findings of this study provide valuable insights into the structure and function of TMEM63 proteins, opening up possibilities for the development of new treatments for diseases such as hearing loss.
Journal Reference:
Qin, Y., Yu, D., Wu, D. et al. Cryo-EM structure of TMEM63C suggests it functions as a monomer. Nat Commun 14, 7265 (2023). https://doi.org/10.1038/s41467-023-42956-2
This discovery has important implications for understanding how genes are turned on and off. The researchers also found that when SETDB1 and H3K9me3 are lost, it leads to changes in how our DNA is organized, affecting gene activity and repetitive elements in our genome. This research provides valuable insights into the mechanisms behind gene regulation and opens up new possibilities for developing targeted therapies to manipulate gene activity, which could be particularly relevant for diseases like cancer.
Journal Reference:
Tam, P.L.F., Cheung, M.F., Chan, L.Y. et al. Cell-type differential targeting of SETDB1 prevents aberrant CTCF binding, chromatin looping, and cis-regulatory interactions. Nat Commun 15, 15 (2024). https://doi.org/10.1038/s41467-023-44578-0