CUHK research: Mitochondria shed their tails like lizards to maintain health

Date: 
2024-04-29
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  • When mitochondria, cells’ energy generators, sense a force, they can pinch off a piece of themselves in a process that’s akin to a lizard shedding its tail.
  • This phenomenon, termed “tail-autotomy fission”, allows mitochondria to remove damaged parts and sustain their health.
 
Mitochondria, a type of specialised subunit within cells, act as the powerhouses, generating the energy needed for cellular activities. The Duan Lab led by Professor Liting Duan in The Chinese University of Hong Kong (CUHK)’s Department of Biomedical Engineering has made a groundbreaking discovery, revealing that mitochondria can break off parts of themselves, mimicking the “self-amputation” behaviour of lizards, and this “tail-autotomy fission” is force-induced. This research was published in the peer-reviewed journal The Proceedings of the National Academy of Sciences (PNAS).
 
What is tail-autotomy fission?
 
Mitochondria are highly dynamic structures within cells that constantly undergo fission and fusion. Mitochondrial fission, similar to cell division, is the process by which one mitochondrion divides into two daughter mitochondria; the opposite process, in which two mitochondria join together to form one mitochondrion, is referred to as mitochondrial fusion. The finely tuned balance of mitochondrial fission and fusion is critical to the maintenance of cell function and health.
 
Contrary to the previous belief that mitochondrial fission occurs randomly, Professor Duan Liting’s team identified a new type of mitochondrial fission with distinct morphological features from canonical fission similar to autotomy. Autotomy is the behaviour by which animals such as lizards, when caught by the tail, shed it in order to escape from predators. The autotomy-like mitochondrial fission that the team denoted tail-autotomy fission features two consecutive naturally occurring steps. First, a thin, tail-like tubule extends out from the bulkier main body. Next, the tubule gets disconnected, resembling the autotomy of a tail.
 
How does tail-autotomy fission occur?
 
Professor Duan’s research team also found that tail-autotomy fission is caused by force. They developed a technique based on the principles of optogenetics, a method that uses light to control cells. By delivering light to mitochondria, the researchers were able to apply physical force to them without the need to actually touch and possibly damage the delicate structures within the cells. The researchers observed that mitochondria can sense the force and respond to it by undergoing tail-autotomy fission.
 
The function of tail-autotomy fission
 
Following tail-autotomy fission, the mitochondrion is divided into a main body and a small tubule. The mitochondria matrix is kept in the former, while the latter carries away the unwanted materials from the outer surface of mitochondria and is degraded via mitophagy, a mechanism of removing damaged mitochondria inside cells. Hence, tail-autotomy is a self-preservation strategy for mitochondria, allowing them to precisely discard unwanted parts of themselves and maintain their health.
 
Professor Duan concluded, “Our research offers new perspectives on the diverse ways mitochondria can maintain their health and functionality, and how they respond to physical forces to regulate their own structure. Understanding this could help us unravel the complexities of cellular health and the mechanisms underlying various diseases.”
 
The full text of the research paper can be found at: https://www.pnas.org/doi/10.1073/pnas.2217019121.

Schematic and fluorescent images of mitochondrial tail-autotomy fission (Scale bars: 2 μm)

Visualisation of force-induced tail-autotomy fission for mitochondrial health maintenance

 

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CUHK develops novel retrievable nanorobots for targeted and enhanced thrombolysis potentially saving stroke patients from brain damage

Date: 
2024-04-02
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A cross-disciplinary research team from The Chinese University of Hong Kong (CUHK) has developed magnetic tissue plasminogen activator (tPA)-anchored nanorobots (tPA-nbots) to treat ischemic stroke. The novel technology exhibits a thrombolysis rate 5 to 20 times faster than traditional treatment and capabilities in recanalising more distal and smaller branches. It demonstrates potential to benefit patients by reducing brain damage and minimising side effects. The team also succeeded in using laser speckle contrast imaging (LSCI) guidance for real-time tracking and delivery of nanorobots and instant monitoring the bloodstream, providing a novel approach for nanorobots-based endovascular intervention therapy. Study results have been published in the international journals Science Advances and Science Robotics.
 
Timely and precise intervention increases the potential for stroke recovery
 
Stroke ranks as the second-leading global cause of death and is the most common cause of adult long-term physical or cognitive disability. tPA is a drug commonly used to dissolve occlusive clots (thrombolysis), restoring blood flow in patients with acute ischemic stroke. However, the unfocused diffusion of high-dose tPA over the whole body undermines the effectiveness of clot lysis and poses a risk of systemic and brain hemorrhage during treatment.
 
Professor Thomas Leung Wai-hong, Head of the Division of Neurology and Lee Quo Wei Professor of Neurology in CU Medicine’s Department of Medicine and Therapeutics, emphasised the importance of prompt and timely re-opening of occluded blood vessels, resuming blood perfusion to the ischemic brain. He stated, “Without treatment, brain cells die at an alarming rate of 1.9 million every minute from stroke onset. While we can now access the main stem of the brain arteries and remove the occlusive clots through catheters, the technological bottleneck is recanalising more distal and smaller branches that are equally vital in preserving brain function. One key challenge is how we can accomplish this goal in a safe and effective manner.”
 
Fast recanalisation by retrievable tPA-nbots for enhanced thrombolysis
 
To address these challenges, a research team with members from the Department of Mechanical and Automation Engineering at the Faculty of Engineering, the Department of Imaging and Interventional Radiology, and the Department of Medicine and Therapeutics at CU Medicine jointly developed retrievable magnetic tPA-nbots. By deploying a tPA-nbot-loaded catheter to the thrombus site, the tPA-nbot microswarm is remotely actuated to the blood clot within vessels of submillimetre size, initiating the tPA-mediated thrombolysis process. After the blood clot is lysed, the tPA-nbots will be guided back for retrieval, ensuring biomedical safety.
 
Professor Zhang Li from the Department of Mechanical and Automation Engineering explained, “The size of tPA-nbots (~300 nm) allows them to be navigated to the thrombus site within the narrow distal blood vessels. The enhanced, localised delivery can prevent high-dose tPA from being circulated in the body, reducing the possibility of systemic and brain hemorrhage. Even with the reduced dosage, the tPA-nbots with both mechanical and chemical etching exhibit a thrombolysis rate 5 to 20 times faster than traditional treatment and save abundant recanalisation time, potentially saving patients from heavy brain damage.”
 
Professor Simon Yu Chun-ho, Emeritus Professor in the Department of Imaging and Interventional Radiology at CU Medicine, explained, “This novel treatment system can potentially deploy nanorobots to the exact location of the thrombus in peripheral and small arteries, which are hardly accessible with catheters alone. Although many technical issues remain to be solved before this technology can be applied in clinical practice, I believe we have taken an important step in the right direction.”
 
Tracking and navigation of microswarm under LSCI to ensure delivery efficiency and biomedical safety
 
To overcome the limitations of current imaging methods in imaging size and spatial-temporal resolution, the team has proposed a strategy using LSCI to enable in vivo real-time tracking and navigation of nanorobots in the endovascular system. LSCI can monitor the changes in the bloodstream within the area of interest and assess reperfusion status after an ischemic stroke. It ensures delivery efficiency and biomedical safety in complex vascular environments, allowing monitoring and analysis of the thrombolysis process, including changes to the state of the blood clot.
 
Dr Bonaventure Ip Yiu-ming, Assistant Professor in the Department of Medicine and Therapeutics at CU Medicine, commented, “Real-time monitoring of the behaviour of nanorobots under physiological conditions is a crucial step to prove their safety and effective delivery. By employing LSCI, we were able to observe and track the movement of nanorobots in both stagnant and flowing blood environments in vessel models, placenta and small animals. This visualisation marks a critical milestone in refining the dose of nanorobots and the distance, strength and angulation of the magnetic field applied. It is essential to carefully optimise these parameters before implementing the technology in humans.”
 
Professor Tony Chan Kai-fung, Research Assistant Professor of the Chow Yuk Ho Technology Centre for Innovative Medicine, added, “The proposed tPA-nbots with high spatial precision provide a promising robotic tool to enhance thrombolysis efficiency and safety, while side effects and treatment time are greatly reduced. It shows the great potential for clinical translation.”
 
The original studies can be accessed here:

(From left) Professor Simon Yu Chun-ho, Emeritus Professor in the Department of Imaging and Interventional Radiology at CU Medicine; Professor Zhang Li, Professor in the Department of Mechanical and Automation Engineering, CUHK; Dr Bonaventure Ip Yiu-ming, Assistant Professor in the Department of Medicine and Therapeutics at CU Medicine; Professor Tony Chan Kai-fung, Research Assistant Professor of the Chow Yuk Ho Technology Centre for Innovative Medicine; and Professor Thomas Leung Wai-hong, Head of the Division of Neurology and Lee Quo Wei Professor of Neurology in CU Medicine’s Department of Medicine and Therapeutics.

Professor Zhang Li explains that the tPA-nbots can be navigated to the thrombus site within the narrow distal blood vessels. The enhanced, localised delivery can prevent high-dose tPA from being circulated in the body, reducing the possibility of systemic and brain hemorrhage, and potentially saving patients from heavy brain damage.

This photo illustrates the ratio of a human hair to nanobots (black dots).

By deploying a tPA-nbot-loaded catheter to the thrombus site, the tPA-nbot microswarm is remotely actuated to the blood clot within vessels of submillimetre size, initiating the tPA-mediated thrombolysis process. After the blood clot is lysed, the tPA-nbots will be guided back for retrieval.

 

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中大研納米機械人減中風損傷

中風為全球的第二大死因,也是導致成人永久傷殘和認知障礙的主因。治療缺血性中風必須分秒必爭,惟現時的治療方法仍有局限性,香港中文大學跨學科研究團隊開發了磁控溶血酶激活劑納米機械人(tPA-nbots),其溶栓速度快5至20倍,亦有望減低缺血引起的腦損傷,及治療的副作用。研究結果已於國際著名學術期刊《Science Advances》和《Science Robotics》上發表

Date: 
Tuesday, April 2, 2024
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AM 730

中大研納米機械人 精準疏通血栓、治腦中風 藉磁力導航、可實時追蹤位置

中大研發新型納米機械人,透過導管放入血管,溶解中風病人的血栓,更精準用藥,相信可為治療提供新方法,研究成果已在國際學術期刊發表。
螢幕上的黑色點點是顯微鏡下的納米機械人,比頭髮還小,由中大團隊研發,可輔助疏通血栓、治療腦中風。機械人在樽內,納米機械人表面帶有藥物,劑量是傳統注射的2.4%,溶解血栓速度較傳統快5至20倍,瞄準血塊更精準用藥。中大機械與自動化工程學系教授張立:「我們發現用單個納米機械人,納米機械人做得很大,它也有可能把血管堵住,對不對?所以我們要盡可能做得小,但是你把納米機械人做得盡量的小以後它也帶不了太多的藥。這樣定向溶栓的好處就是這個藥物不是在人體裏面進行循環,它就是在這個位置,然後到大腦。它並沒有在大腦裏面循環的話,會大大降低人體其他部位內出血的機會。」
Date: 
Tuesday, April 2, 2024
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Powering the world with greener batteries CUHK Professor Lu Yi-chun receives Hong Kong Engineering Science and Technology Award 2023

Date: 
2024-03-20
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Professor Lu Yi-chun, Professor of the Department of Mechanical and Automation Engineering at The Chinese University of Hong Kong (CUHK), has been awarded the Hong Kong Engineering Science and Technology Award (HKEST Award) 2023 by the Hong Kong Academy of Engineering Sciences for her accomplishments and contributions in materials science, engineering and energy engineering, particularly sustainable battery technology.
 
CUHK’s Pro-Vice-Chancellor Professor Sham Mai-har extended her heartfelt congratulations to Professor Lu. She said, “Professor Lu’s groundbreaking work in sustainable battery technology has contributed to a greener future for the earth. It also aligns with CUHK’s efforts to create societal impact through research and innovation. This recognition once again acknowledges the University’s dedication to creating knowledge and pushing the boundaries of innovation.
 
Professor Lu was honoured by the recognition and stated that she and her team will continue to advance energy storage technology for a future of safe, sustainable energy.  
 
Professor Lu has made ground-breaking contributions in engineering science and technology, focusing on sustainable battery technology, to address global warming. Her work in developing advanced, environmentally friendly battery technologies aligns closely with global efforts towards sustainable energy solutions. Her key innovations include developing molecular crowding electrolytes for high-voltage aqueous batteries and pioneering the world’s first low-cost, high-power, polysulphide-based flow battery with a novel charge-reinforce ion-selective membrane and biomimetic molecular catalyst. These projects represent examples of technology transfer and commercialisation.
 
Professor Lu’s contributions extend beyond the laboratory, impacting both the academic and commercial sectors in engineering science and technology. In 2020, she co-founded Luquos Energy, a start-up incubated by CUHK, focusing on scalable, safe, sustainable battery technologies for grid storage. Luquos Energy was chosen as one of the Top 10 Flow Battery Startups to Watch in 2023 by the StartUs Insights Discovery Platform, an international data-science platform.
 
About the Hong Kong Academy of Engineering Sciences and the Hong Kong Engineering Science and Technology Award
 
The Hong Kong Academy of Engineering Sciences (HKAES), comprising leaders of the Hong Kong engineering community, aspires to play a leading role in promoting the development of engineering science and technology in Hong Kong, including the nurturing of local talents and professionals for a vibrant innovation and technology industry. With the support of the Innovation and Technology Commission of the HKSAR, the Academy launched the Hong Kong Engineering Science and Technology Award (HKEST Award) in 2022 to recognise young scientists, engineers and technologists from diverse disciplines who have excelled in developing creative solutions to problems through research, development, innovation and entrepreneurship, and have made significant advancements to the betterment of society. Up to six nominees will be selected to receive the Award.

Professor Lu Yi-chun and team

Professor Lu Yi-chun displays the green battery prototype developed at CUHK.

 

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Faculty of Engineering organized “2023 CUHK–Mainland Optics & Photonics Workshop

Date: 
2023-12-29
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2023 CUHK–Mainland Optics & Photonics Workshop successfully took place at Faculty of Engineering during 15-17 December 2023. The three-day in-person workshop provided a free platform for academic and social interactions, joined by over 30 distinguished scholars and up to one hundred graduate students and postdoctoral fellows from Tsinghua University, CUHK, Zhejiang University, and other renowned universities/institutions in the mainland. 
 
Coordinated by Prof. Renjie Zhou (Assistant Dean for Research, Faculty of Engineering) and supported by Prof. Xiankai Sun and Chaoran Huang (Department of Electronic Engineering), Prof. Scott Yuan (Department of Biomedical Engineering), and many other colleagues in Faculty of Engineering, the workshop further fostered the existing collaborations between CUHK and mainland partners, while exploring new frontiers in research innovations and new initiatives in cultivating the next generation of leaders in the field of optics and photonics. The attendants include Prof Songlin Zhuang (Member, Chinese Academy of Engineering), Prof. Xu Liu (Distinguished Professor, Zhejiang University), Prof. Siyuan Yu (Distinguished Professor, Sun Yat-sen University), Prof. Hon Ki Tsang (Interim Dean, Faculty of Engineering), Prof. Jian-Bin Xu (Associate Dean for Research, Faculty of Engineering), Prof. Lian-Kuan Chen (Director, Lightwave Communications Laboratory), etc.  

 

Workshop group photoe

Gift to Prof. Songlin Zhuang, Honorary Chairman of Chinese Society for Optical Engineering

 

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CUHK develops new modular magnetic microrobot to deliver cells into the bile duct for targeted therapy

Date: 
2024-01-24
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A collaborative research team led by Professor Zhang Li from the Faculty of Engineering, and Professor Philip Chiu Wai-yan and Professor Tony Chan Kai-fung from the Faculty of Medicine (CU Medicine) at The Chinese University of Hong Kong (CUHK), with Professor Joseph Sung Jao-yiu from Nanyang Technological University, who is also an emeritus professor at CU Medicine, has developed a modular microrobot with lockable and detachable modules, which provides a powerful propulsive force for targeted cell delivery in the bile duct without leaving any non-degradable materials inside it. This collaborative work was published recently in the renowned international research journal Science Advances.
 
Challenges for microrobots in simultaneously achieving strong actuation capability, multifunctionality and long-term biosafety
 
Currently, cell-based therapy in the biliary tract or liver can delivered through vascular routes or endoscopy. However, the majority of the cells do not reach the targeted region due to the non-specific delivery. Magnetic microrobots could potentially revolutionise minimally invasive, cell-based therapy due to their unique advantages, such as the ability to navigate regions inside the human body that are inaccessible by conventional medical tools. However, while navigating mucous environments, integrating desirable multi-tasking capabilities into such a miniature device and guaranteeing the long-term biosafety of high-dose magnetic materials pose significant challenges.
 
Modular design of microrobots with uncompromised multifunctionality 
 
The modular magnetic microrobot designed by the research team has overcome the bottleneck for using magnetic microrobots for biomedical applications. It provides a strategy to simultaneously endow microrobots with superior magnetic actuation capabilities and cellular function without compromising either, allowing for the future development of minimally invasive, targeted cell-based therapy for bile duct diseases. 
 
Professor Zhang, Professor in the Department of Mechanical and Automation Engineering, explained, “The modular microrobot is a combination of magnetic actuation (MA) and cell scaffold (CS) modules, which are similar to a rocket and a satellite, respectively. The MA module functions as the propulsion and control component, while the CS module provides capabilities for cell loading and biodegradability, facilitating targeted therapy. The MA module (rocket) and CS module (satellite) separate after reaching the target site. The MA module, consisting of a high dose of magnetic materials, is retrieved using an endoscope, after navigating back to the deploying catheter afterwards, minimising unexpected hazards. With such a retrievable design, we could use high-dose magnetic materials to combat the dynamic, mucus-like biological environment of the gastrointestinal tract, allowing more effective and efficient delivery of cell therapy. This approach holds potential for the specific treatment of biliary disease.”
 
Professor Sung, CUHK Emeritus Professor of Medicine, Dean of Lee Kong Chian School of Medicine, and Senior Vice President (Health and Life Sciences), Nanyang Technological University, Singapore, remarked, “This is like science fiction come true. The new microrobot offers a minimally invasive approach to body systems that are otherwise inaccessible to medical interventions. It can potentially be developed to treat inflammatory and/or malignant conditions. We have successfully validated our concept in vivo using rabbit models, and demonstrated the effectiveness of magnetic navigation, on-demand disassembly and post-operational retrieval.”
 
Professor Chiu, Director of the Chow Yuk Ho Technology Centre for Innovative Medicine, CU Medicine, commented, “In this collaborative research work, we demonstrated a new approach using a modular magnetic microrobot for cell delivery in the bile duct, which realises direct endoluminal delivery of cells into the targeted region in the biliary tract and sustainable cell/drug release to lesions. It also eliminates the potential risk of residual high-dose magnetic materials. This opens up a new door for endoluminal cell-based therapy of bile duct diseases.”
 
Professor Chan, Research Assistant Professor of the Chow Yuk Ho Technology Centre for Innovative Medicine, added, “The modular design allows the microrobots to be combined with different modules, extending their potential functions with respect to different applications. We also demonstrated the compatibility of modular microrobots with medical imaging modalities available in hospitals, such as X-ray fluoroscopy and ultrasound imaging, paving the way for clinical translation. We are now working closely to translate the technology for various application sites inside the body.”
 
The team envisions that the development of the modular microrobots will lead to a promising minimally invasive microrobotic platform that offers high efficiency and safety for various endoluminal interventions, as well as diverse functionality with high clinical value.
 
(extracted from the press release issued on 25 Jan 2024 by CUHK Communications and Public Relations Office)
 

The modular microrobot is a combination of magnetic actuation (MA) and cell scaffold (CS) modules, which is designed for targeted delivery in tiny lumens.

The actual size of the modular microrobot.

Professor Zhang Li (first row, first right), Professor Tony Chan Kai-fung (second row, second right) and the research team.

 

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Congratulatory Photo taking with CUHK Robocon Team 2023

Date: 
2024-01-15
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Hong Kong Science and Technology Parks Corporate (HKSTP) and Radio Television Hong Kong (RTHK) had announced a significant partnership at their collaboration agreement signing ceremony held on 5 January 2024 (Friday), with the aim to drive advancements in digital innovation and empower the future of next generation leaders. 
 
Way forward strategies especially with Robocon had been elaborated at the Ceremony. HKSTP and RTHK will tap into Hong Kong’s AI and Robotics (AIR) talent by jointly organising the International ABU Robocon in 2026. By hosting the regional competition, HKSTP and RTHK hope to nurture cross-disciplinary expertise in AI and robotics among education institutions and boost the city’s standing as a hub for world-class AI and broader I&T development.
 
Being the Champion of Robocon Hong Kong Contest 2023, “The Lord of the Rings” team from CUHK represented Hong Kong at the ABU Robocon 2023 in last August and defeated 13 champion teams to win the first runner-up and the Best Design Award. To recognize the excellent performance of CUHK Team, the CUHK Robocon Team 2023 was invited to join and witness the kickstart of this meaningful alliance, a congratulatory photo was taken at the Ceremony. 
 

Champion of Robocon Hong Kong Contest 2023, “The Lord of the Rings” team from CUHK. Guests (second row, from left): Professor Tsang Hon Ki, Interim Dean of Engineering, CUHK; Ir Dr HL Yiu, Chief Corporate Development Officer of HKSTP; Albert Wong, CEO of HKSTP; Professor Sun Dong, Secretary for Innovation, Technology and Industry; Eddie Cheung, Director of Broadcasting; Raymond Sy, Deputy Director of Broadcasting; Natalie Chan, Assistant Director of Broadcasting (TV & Corporate Businesses), and Dr Crystal Fok, Head of STP Platform of HKSTP

 

 

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