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Jian Liu’s group published a collaborative research article in Nature Communications

Jian Liu’s group published a collaborative research article in Nature Communications

Recently, Dr. Jian Liu’s group from Zhejiang University-University of Edinburgh Institute (ZJE) and the collaborators, Pro. Shiqun Shao from College of Chemical and Biological Engineeringof Zhejiang University, published an article entitled “A plug-and-play monofunctional platform for targeted degradation of extracellular proteins and vesicles” in Nature Communications. https://doi.org/10.1038/s41467-024-51720-z Existing strategies use bifunctional chimaeras to mediate extracellular protein degradation. However, these strategies rely on specific lysosome-trafficking receptors to facilitate lysosomal delivery, which may raise resistance concerns due to intrinsic cell-to-cell variation in receptor expression and mutations or downregulation of the receptors. Another challenge is establishing a universal platform applicable in multiple scenarios. Here, the research team develops MONOTAB (MOdified NanOparticle with TArgeting Binders), a plug-and-play monofunctional degradation platform that can drag extracellular targets into lysosomes for degradation. MONOTAB harnesses the inherent lysosome-targeting ability of certain nanoparticles to obviate specific receptor dependency and the hook effect. To achieve high modularity and programmable target specificity, the streptavidin-biotin interaction is utilized to immobilize antibodies or other targeting molecules on nanoparticles, through an antibody mounting approach or by direct binding. This study reveals that MONOTAB can induce efficient degradation of diverse therapeutic targets, including membrane proteins, secreted proteins, and even extracellular vesicles.  Targeted degradation of extracellular proteins or vesicles mediated by MONOTABsPro. Shiqun Shao and Pro. Jian Liu are the corresponding authors. In addition, the PhD student Qian Tang (ZJE, 2021 entry) participated in this research as the co-first author. About Jian Liu’s labJian Liu's group is now interested in investigating lung squamous cell carcinoma development and treatment using genetic mouse models and AI+ multi-omics, especially the research direction on cancer immunology and 3D genome. He has published over 50 papers, including publications in the past three years, as a co-corresponding author in Nature Communications (2), Advanced Science, Oncogene, Molecular Oncology journals. Moreover, his lab developed a multi-omics web database Omics3D (http://omics3d.net/) to investigate the de novo functional genome during cancer development.Email:JianL@intl.zju.edu.cnJian Liu’s lab (https://person.zju.edu.cn/liujian) is recruiting postdoc and Ph.D. students, including the single degree from University of Edinburgh.
2024-08-24
Dr. Zhi Hong’s group published an article in the Journal of Cell Biology, revealing novel protein tethers in facilitating mitochondrial hitchhiking

Dr. Zhi Hong’s group published an article in the Journal of Cell Biology, revealing novel protein tethers in facilitating mitochondrial hitchhiking

Organelles engage in signal transduction and material exchange through membrane contact sites, which play significant roles in lipid synthesis, calcium ion transfer, and autophagy. Mitochondria have been widely reported to form contact sites with the endoplasmic reticulum (ER), referred to as mitochondria-ER contact sites (MERCs). Early studies suggested that mitochondrial fusion proteins Mitofusin 1 and 2 (MFN1/2) function as physical linkers at these contact sites by forming dimers with MFN2 on the ER. However, super-resolution imaging of MFN2 fails to detect MFN2 signal on ER membranes. Thus, the model that ER-MFN2 dimerizes with mitochondrial-MFN2 requires re-examination.Recent findings propose that MFN2 specifically transports phosphatidylserine (PS) from the ER to mitochondria for the synthesis of phosphatidylethanolamine (PE), further indicating MFN2's potential involvement in multiple functions at MERCs. Whether all these functions are mediated by MFN2-MFN2 dimers and whether other unknown ER proteins participate with MFN2 remains unresolved. Therefore, identifying new ER protein partner for MFN2 and elucidating their biological functions will help in reevaluating the role of MFN2-MFN2 homodimers in mediating MERCs and functions related.On 12 August 2024, Dr. Zhi Hong's group at ZJE published an article titled "Dynamic interaction of REEP5-MFN1/2 enables mitochondrial hitchhiking on tubular ER" in the Journal of Cell Biology. This study is the first to reveal that the ER-shaping protein REEP5, as a novel interacting partner of MFN1/2, mediates the mitochondrial hitchhiking on the tubular ER, ultimately achieving uniform mitochondrial distribution throughout cytoplasm and regulating cellular reactive oxygen species (ROS) homeostasis.Previous results indicated that knockdown or knockout of REEP family members in the ER leads to mitochondrial dysfunction. Thus the study initially performed a small-scale screening of the REEP protein family, discovering that REEP5 specifically binds MFN1/2. Live-cell imaging further confirmed the enrichment of REEP5 and MFN1/2 at MERCs. The Using GI-SIM super-resolution live imaging, ER and mitochondria displayed a dynamic “association-dissociation” pattern, with REEP5-MFN2 tethers driving mitochondrial hitchhiking on the tubular ER. The study found that weakening REEP5-MFNs interactions leads to mitochondrial collapse to the perinuclear region. Interestingly, when REEP5-MFNs interactions are locked, mitochondrial can no longer be randomly released from tubular ER, they remained attached to the ER instead and resulting in mitochondrial hyperfusion. The findings suggest that the dynamic binding between REEP5 and MFN1/2 underlies the molecular mechanism of dynamic ER-mitochondria contact.Previous studies have shown that the subcellular localization of mitochondria is closely related to mitochondrial ROS homeostasis. Using the mitochondrial-localized ROS sensors roGFP2 and HyPer7, the researchers found that mitochondrial ROS level is tightly regulated by REEP5-MFN1/2 tethering strengths, e.g. mitochondrial ROS is upregulated once REEP5-MFN1/2 tethering is disrupted.In summary, this study elucidates a novel mechanism by which the REEP5-MFN1/2 protein complex facilitates mitochondrial "hitchhiking" along the tubular ER, thereby promoting uniform mitochondrial distribution within the cell and regulating cellular ROS homeostasis. The findings offer theoretical evidence suggesting that organelle interactions are intrinsically dynamic processes featured by cycles of association and dissociation.Dr. Zhi Hong from ZJE serves as the corresponding author, with Dr. Shue Chen and Ph.D. candidate Yang Sun as co-first authors. Additionally, Ph.D. candidates Lan Yang and Yuling Qin from ZJE contributed significantly to this study. This research received support from the National Natural Science Foundation of China.Link to the paper: https://doi.org/10.1083/jcb.202304031About Dr. Zhi Hong’ labDr. Zhi Hong’s research group focuses on organelle interactions and cellular homeostasis, as well as investigating the molecular mechanisms and biological functions related to lipid metabolism. Their findings have been published in esteemed journals such as the Journal of Cell Biology, Cell Research, Autophagy, and Antiviral Research.
2024-08-23
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Jin Yinhua, Rush towards every passion

She is a lovely girl from Northeast China, gentle towards all things in the world. She approaches science with reverence, delving into the mysteries of life. Using her soul to ignite the fireworks in her aspirations, she decorates the joys of life with her actions. In this edition, we introduce Dr. Jin Yinhua, a researcher and doctoral supervisor at ZJE."Dr. Jin YinhuaResearcher, PhD Supervisor, Tenure-Track Assistant ProfessorDr. Jin Yinhua graduated from the University of Heidelberg in Germany under the guidance of Prof. Dr. Bruce A. Edgar. She subsequently pursued postdoctoral training at Stanford University School of Medicine in the United States, mentored by Prof. Dr. Roel Nusse, a fellow of the National Academy of Sciences and an HHMI investigator. During this period, her research focused on elucidating the mechanisms by which signals from the stem cell microenvironment regulate tissue homeostasis and regeneration.By establishing a unique set of genetic, cellular, and molecular biology tools, she first revealed the mechanisms through which microenvironmental signals such as EGF and Wnt control the potential of stem cells, as well as the roles of these mechanisms in tissue regeneration and repair. In May 2023, Dr. Jin Yinhua joined Zhejiang University-University of Edinburgh Institute as a researcher and PhD supervisor. She formed the Stem Cell Microenvironment and Tissue Regeneration research group, where she primarily investigates how microenvironmental signals control cell behavior and cell interactions during tissue development and regeneration.ACADEMIC CAREERThe journey of learning began in 2003 when the Human Genome Project was nearing completion, planting the seeds of ideals in the young and tender heart. The seeds, imbued with vibrant vitality, quickly took root and sprouted, breaking through the soil, fueled by curiosity, exploration, and the quest for knowledge. Starting with the study of biotechnology at China Agricultural University, focusing on the application of technology in production, to researching plant stem cells at Seoul National University, and further delving into adult stem cells and understanding the regulation of intestinal stem cells by growth factors at the University of Heidelberg. Then, journeying to Stanford University to continue in this field, Dr. Jin, like a helmsman, held the oar, steered the course, adjusted the direction, cut through waves, and sailed towards the ideal shore.In the pursuit of biology, Dr. Jin Yinhua's journey began with interest, and she consistently nurtured that interest with the purest passion, focusing single-mindedly on watering and cultivating it. Over the years, that initial interest quietly shed its youthfulness and transformed into a deep-seated aspiration.During her academic journey, Dr. Jin Yinhua was influenced by the diligent efforts of Korean students, admired the rigorous, meticulous, and high-standard work attitude of German researchers, and was amazed by the active thinking, daring spirit, and courage to tackle cutting-edge work displayed by American researchers. Under the influence of a multicultural environment, Dr. Jin Yinhua embraced the strengths of various cultures, developed her style, and explored infinite truths in the endless river of the universe.Behind Dr. Jin Yinhua's calm and easygoing narrative, there ripples the unknown hardships and challenges. Cultural clashes, language barriers, and unfamiliar environments are tests that every international student must face. The comforting language rules, habits, and ways of thinking in one's native tongue can become barriers and misunderstandings in cross-cultural communication. In other words, what was once familiar and understood has turned into confusion.Courage is the belief that life holds onto in difficult times, a belief that time endows with enduring resilience. On this note, Dr. Jin Yinhua also provides advice: bravely step out of the comfort zone of the Chinese community, communicate more with locals, and embrace each other's cultural habits. This is indeed something that takes time and effort, but it is worth doing.SCIENTIFIC RESEARCH JOURNEY"Passionate, enjoyable, challenging" is Dr. Jin Yinhua's summary of her journey in scientific research. Maintaining a childlike curiosity is the driving force for researchers. The pursuit originates from love, and love achieves the pursuit. The scientific research career begins with curiosity and passion, and what is most precious is retaining the initial expectation after experiencing numerous challenges. In our conversation with Dr. Jin Yinhua, we can feel her passion for research and enjoyment of the process. She attributes this to the influence of two mentors.Her American mentor, despite being elderly, left a deep impression on Dr. Jin with his pure passion. His relentless pursuit of truth, continuous progress, and unwavering commitment inspired her. "Life gains value when you can find joy in your profession," he once said. Scientific research is challenging, but we can still find enjoyment in it.Her German mentor, on the other hand, is someone who truly enjoys scientific research. He finds pleasure in the seriousness of research, immersing himself in the process with a philosophical mindset and a comfortable and relaxed state. Despite the difficulties of scientific research, he manages to derive enjoyment from it, showcasing a unique approach to the scientific journey.THE JOURNEY OF LIFE Andrew Carnegie once said, "Everyone should have a strong interest or hobby to enrich the soul and add flavor to life." Wise individuals can make ordinary lives vibrant and colorful. Volleyball, comics, books, movies, travel, and everyday meals and seasons are all cherished as the most beautiful scenery in Dr. Jin Yinhua's heart, enriching her life beyond scientific research. Dr. Jin enjoys playing volleyball, having been a member of the university team at China Agricultural University, and participating in intercollegiate volleyball competitions with friends, a joyful and satisfying experience.What stands out most in Dr. Jin Yinhua's memories? Undoubtedly, it's travel. Leafing through the pages of her life, she realizes that many unforgettable memories are closely tied to her travels. Whether it's reaching for the stars in accessible Alaska, the romantic encounter with the aurora and snow near the Arctic Circle, or personally visiting the small village mentioned in the textbook's "The Last Lesson" and experiencing the wonderful overlap of reality and memory. Dr. Jin particularly emphasizes that compared to short-term tourist visits, the long-term immersive travel experienced during her overseas studies made it easier to discover vibrant corners and encounter unexpected beauty.For undergraduate students, Dr. Jin Yinhua's message is: "The guidance of good mentors is like a lighthouse at sea, guiding lost ships. Dr. Jin Yinhua wants to say to our undergraduate classmates, 'It should be a fun journey, enjoy it.' She plainly states that looking back on her academic journey, the undergraduate phase was undoubtedly the most interesting. Therefore, undergraduate students should wholeheartedly enjoy this period, striking a balance between diligent learning and embracing the pleasures of life. Fear not the length of youth, and let's explore new horizons while the fire is still burning, sipping poetry and wine in the bloom of our time!"

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Aaron Irving, Befriending Biology, Keeping up with Interests

Aaron IrvingAaron Irving, Assistant Professor at the Zhejiang University-University of Edinburgh Institute (ZJE). His journey into the world of life sciences began with a movie and a deep connection to China.Dr. Aaron Irving, an Assistant Professor at ZJE, brings a wealth of academic and research experience from his training at institutions like the University of Queensland (Australia), Diamantina Institute (UQ Australia), Monash Biomedicine Discovery Institute (Melbourne), and the Duke-NUS Medical School (Singapore).Dr. Irving's focus lies in newly emerging zoonotic viral infections and the host-pathogen interactions they trigger. He uses bats as a model organism, exploring key factors in bat immune responses that could be harnessed to enhance human immunity against pathogens. His lab also works on new diagnostic techniques to identify wildlife infections with zoonotic viruses like SARS-CoV-2 and factors contributing to the potential for zoonotic diseases.But what led Aaron to this fascinating field of virology? It all started with a childhood fascination with viruses, but it was a movie that changed the course of his life. The film "Outbreak," which tells the story of the Ebola virus jumping from monkeys to humans and spreading among the population, convinced him to become a research scientist. With curiosity about viruses and a concern for human health, he embarked on the path of scientific research.During his undergraduate years, Aaron pursued a Bachelor of Science degree, allowing him to freely explore his interests and build a solid foundation in biology. He worked diligently, fueled by passion and guided by his interests, eventually earning dual degrees in molecular biology and cell biology.After his undergraduate studies, he continued for an additional year of research (known as an Honours degree in Australia) and achieved the highest honors (Class I). During this time, he delved into the study of the herpes simplex virus (HSV1), which causes cold sores, and how it evades the human immune system. This research laid the groundwork for his future career in host-pathogen interactions.When it comes to bats, Aaron's eyes light up with excitement. "Bats are truly fascinating creatures," he says. What makes Aaron so enamored with these flying mammals?Initially, Aaron was not well-acquainted with the mysteries of bats. However, he stumbled upon a new world that captured his interest. Bats have undergone many evolutionary adaptations, making them exceptionally healthy, robust, and resilient animals with strong immune systems, immunity to aging, cancer resistance, inflammation prevention, and autoimmune disease avoidance. Aaron's research on bats aims to uncover the secrets of their exceptional health and apply that knowledge to benefit human health.Today, Aaron is involved in various projects, including those related to coronaviruses. His primary focus is on understanding the different genes that bats activate in their immune responses and comparing them to humans.One of his most intriguing projects examines the differences between bat and human aging. According to Aaron, wild-caught bats show no signs of aging, with 20-year-old bats appearing as youthful as 1-year-olds. He hopes to compare this phenomenon with research on human aging and humorously suggests that the findings could potentially be applied to skincare products to prevent human skin aging.Before joining ZJE, Aaron had already established a connection with China. He had previously visited Yunnan, known as the "Kingdom of Flora and Fauna," and collaborated with a local organization. He describes Yunnan as an incredible place with diverse biological species, making bat capture relatively easy due to the vast bat populations in a small area.When asked why he chose ZJE, Aaron believes that science in China is rapidly growing, offering abundant opportunities and possibilities. ZJE warmly welcomes fresh talent and provides excellent research facilities and an environment conducive to teaching. Additionally, the international platform at ZJE allows him to adapt and integrate into a foreign culture. Despite being a newcomer, he appreciates the students' critical thinking abilities and their knack for posing thought-provoking questions, which continually surprise him. He encourages students to express their opinions boldly and actively participate in the classroom.

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Dmytro Shytikov, A dreamer with a heart of gold

Dmytro ShytikovDr. Dmytro Shytikov is from Ukraine and is currently a lecturer at ZJE. He graduated with his PhD from Kiev National University in 2015, focusing on the mechanisms of immune response, the interaction of the adaptive immune system with the natural immune system, and the mechanisms of aging of the immune system.Dmytro started his research at university by joining Prof. Gennadii Butenko's lab, a team that studied the effects of blood exchange between animals of different ages, focusing on the immune system, which got Dmytro interested in the field of immunity, and guided him on an exploratory journey to study the immune system from then on.In 2016, Dmytro came to China and joined the School of Basic Medical Sciences at Zhejiang University for a postdoctoral position. In a country where most people tend to go to Western countries to pursue research, coming to China to do research seemed like a "surprising choice." "But why not go? I'm enjoying everything here," Dmytro says with a smile. Dmytro joined ZJE in April 2021. Dmytro believes that ZJE's model of talent development is markedly different from where he went to school, with significant crossover and a cutting-edge curriculum of integrated courses for students.During his time at ZJE, Dmytro has learned a lot of new things, especially about statistics (which he thinks is very important), and he has met many friendly colleagues, which has made him enjoy his research and life at ZJE even more. Dmytro is mainly responsible for the Biomedical Horizon course at ZJE, an interdisciplinary course that brings together the expertise of both ZJU and the University of Edinburgh to explore the potential of the Biomedical Horizon. Edinburgh University to explore how biomedicine can be used to address the challenges facing the world. The students enjoy his classes very much, and all see Dmytro as a friendly and fun teacher who loves in front of life. He had a lively approach to his classes, encouraging people to express themselves and guiding his classmates to solve problems independently. But when it comes to students' work, Dmytro is very serious, students can not only learn professional knowledge from him but also be infected by his rigorous attitude!Although busy is Dmytro's daily routine, work is not all he does. In his leisure time, Dmytro reads, plays sports, takes walks with his wife, and does origami and postcrossing (postcard exchange). To understand Chinese culture and integrate into his new environment, Dmytro has tried to learn Chinese and happily accepted the Chinese name "Shi Mingcheng" which a friend suggested for him. "It sounds and looks good! My original name was a bit long," he jokes. This year, Dmytro and his wife experienced an authentic Chinese New Year, spending New Year's Eve with their twinned Haining family over a hot pot, and Dmytro thoughtfully prepared the ingredients to teach everyone how to make Ukrainian dumplings. That night, everyone sat around and had a great time talking about Eastern and Western cultures and Chinese New Year customs.When it comes to the future, Dmytro hopes to become a researcher in the field of immunology and explore more deeply in immunotherapy. This is his second year as a lecturer, and there are many memorable experiences and much-needed updates that he hopes to pass on to his students in a way that is recognized by ZJE. At the same time, he looks forward to learning more Chinese and experiencing Chinese culture more deeply in the future.

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Qianting Zhang, 90s Newcomer PhD Supervisor

Qianting Zhang2007-2017 Undergraduate degree, College of Life Sciences, Zhejiang University2017-2018 Postdoctoral Fellow, University of Gothenburg2020.4 Assistant Professor, Zhejiang University-University of Edinburgh (ZJE)She focuses on signal regulation and molecular mechanisms during mammalian gametogenesis or tumourigenesis using mammalian cells, gene-edited mouse models and human samples.Zhejiang University personal homepage: https://person.zju.edu.cn/qiantingzhangPersonal Email: qiantingzhang@intl.zju.edu.cnIn her long academic journey,  Qianting  Zhang never imagined she would have an unbreakable bond with Zhejiang University - obtaining her bachelor's and doctoral degrees, building a family, and returning as an independent researcher at the Zhejiang University-University of Edinburgh (ZJE). At every turning point in life, she coincidentally encountered Zhejiang University's proactive establishment of new academic institutions, providing favorable conditions and flexible space for individuals like Teacher Zhang to pursue their life ambitions.In response to the needs of the new era, where world-class university construction and the globalization of education and research are essential, Zhejiang University established an international campus in Haining, offering Teacher Zhang another opportunity and the confidence to return to her alma mater. She says, "I have always chosen Zhejiang University because opportunities kept coming my way. Additionally, many mentors, friends, and advisors at Zhejiang University have been instrumental in propelling my career forward."Research has always been Qianting  Zhang's pursuit, and her path in early-stage tumor development and the molecular mechanisms of mammalian gametogenesis, especially during 2018 and 2019, led to the publication of numerous articles in renowned journals like Nature Cell Biology. To outsiders, it may seem like an extraordinary amount of energy and time to achieve so much in just two years. Yet, Qianting  Zhang modestly attributes it to "coincidence." She says, "Each research project has a long cycle, such as my work with gene knockout mice, where good samples appeared in the past two years, and that's when the articles were published." She further emphasizes that research is not a solo effort; it requires continuous dedication, hard work, and contributions from numerous collaborators at every stage.For many, research may appear tedious and unexciting, a sentiment shared by Qianting  Zhang when she first entered university. She initially chose biology due to her passion for the subject, but she initially had doubts and uncertainties about research. Nevertheless, she firmly believed in "loving what you do" and persevered in improving her expertise. When faced with challenges in research projects, she approached problems with a rational mindset, conquered her negative emotions, and sought solutions. She stresses the importance of being open to changing directions when necessary, emphasizing the value of timely communication with mentors and considering problems from different angles.Qianting  Zhang believes that research and education complement and are inseparable from each other. Having top-notch scientists and significant advancements in research is important, but it is equally crucial to prioritize the cultivation of excellent students and research professionals. Disseminating advanced scientific concepts systematically and enhancing the creativity of the entire research team is essential for maintaining international competitiveness and becoming pioneers in the forefront of life sciences.As an Assistant Professor, Qianting  Zhang's role includes helping the institute design cutting-edge, technology-driven professional courses and exploring diversified higher education models. Beyond the classroom, she mentions that thanks to the rich educational model, many students have a strong foundational knowledge and different perspectives on classroom discussions. They actively participate and often provide unique insights, which is why she loves teaching.

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