The Cryo-EM structure of the yeast replisome in complex with FACT and parental histones (A) and its atomic model (B). Credit: Nature (2024). DOI: 10.1038/s41586-024-07152-2

A research team has recently made a significant breakthrough in understanding how the DNA copying machine helps pass on epigenetic information to maintain gene traits at each cell division.

Understanding how this coupled mechanism could lead to new treatments for cancer and other epigenetic diseases by targeting specific changes in gene activity. Their findings have recently been published in Nature.

Our bodies are composed of many differentiated cell types. Genetic information is stored within our DNA,which serves as a blueprint guiding the functions and development of our cells. However, not all parts of our DNA are active at all times. In fact, every cell type in our body contains the same DNA, but only specific portions are active, leading to distinct cellular functions.

For example, identical twins share nearly identical genetic material but exhibit variations in physical characteristics, behaviors and disease susceptibility due to the influence of epigenetics. Epigenetics functions as a set of molecular switches that can turn genes on or off without altering the DNA sequence. These switches are influenced by various environmental factors, such as nutrition, stress, lifestyle, and environmental exposures.

In our cells, DNA is organized into chromatin. The nucleosome forms a fundamental repeating unit of chromatin. Each nucleosome consists of approximately 147 base pairs of DNA wrapped around a histone octamer which is composed of two H2A-H2B dimers and one H3-H4 tetramer.

During DNA replication, parental nucleosomes carrying the epigenetic tags, also known as histone modifications, are dismantled and recycled, ensuring the accurate transfer of epigenetic information to new cells during cell division. Errors in this process can alter the epigenetic landscape, gene expression and cell identity, with potential implications for cancer and aging.

Despite extensive research, the molecular mechanism by which epigenetic information is passed down through the DNA copying machine, called the replisome, remains unclear. This knowledge gap is primarily due to the absence of detailed structures that capture the replisome in action when transferring parental histones with epigenetic tags.

Studying the process is challenging because of the fast-paced nature of chromatin replication, as it involves rapid disruption and restoration of nucleosomes to keep up with the swift DNA synthesis.

In previous studies, the research team made significant progress in understanding the DNA copying mechanism, including determining the structures of various replication complexes. These findings laid a solid foundation for the current research on the dynamic process of chromatin duplication.

This time, the team achieved another breakthrough by successfully capturing a key snapshot of parental histone transfer at the replication fork. They purified endogenous replisome complexes from early-S-phase yeast cells on a large scale and utilized cryo-electron microscopy (cryo-EM) for visualization.

They found that a chaperone complex FACT (consisting of Spt16 and Pob3) interacts with parental histones at the front of the replisome during the replication process. Notably, they observed that Spt16, a component of FACT, captures the histones that have been completely stripped off the duplex DNA from the parental nucleosome. The evicted histones are preserved as a hexamer, with one H2A-H2B dimer missing.

Another protein involved in DNA replication, Mcm2, takes the place of the missing H2A-H2B dimer on the vacant site of the parental histones, placing the FACT-histone complex onto the front bumper of the replisome engine, called Tof1. This strategic positioning of histone hexamer on Tof1 by Mcm2 facilitates the subsequent transfer of parental histones to the newly synthesized DNA strands.

These findings provide crucial insights into the mechanism that regulates parental histone recycling by the replisome to ensure the faithful propagation of epigenetic information at each cell division.

The research was led by Professor Yuanliang Zhai at the School of Biological Sciences, The University of Hong Kong (HKU) collaborating with Professor Ning Gao and Professor Qing Li from Peking University (PKU), as well as Professor Bik-Kwoon Tye from Cornell University.

This study involved a collaborative effort that spanned nearly eight years, starting at HKUST and concluding at HKU. Professor Zhai said, “It only took us less than four months from submission to Nature magazine to the acceptance of our manuscript. The results are incredibly beautiful. Our cryo-EM structures offer the first visual glimpse into how the DNA copying machine and FACT collaborate to transfer parental histone at the replication fork during DNA replication.

“This knowledge is crucial for elucidating how epigenetic information is faithfully maintained and passed on to subsequent generations. But, there is still much to learn. As we venture into uncharted territory, each new development in this field will represent a big step forward for the study of epigenetic inheritance.”

The implications of this research extend beyond understanding epigenetic inheritance. Scientists can now explore gene expression regulation, development, and disease with greater depth. Moreover, this breakthrough opens up possibilities for targeted therapeutic interventions and innovative strategies to modulate epigenetic modifications for cancer treatment.

As the scientific community delves deeper into the world of epigenetics, this study represents a major step toward unraveling the complexities of replication-coupled histone recycling.

More information:
Ningning Li et al, Parental histone transfer caught at the replication fork, Nature (2024). DOI: 10.1038/s41586-024-07152-2

Secretin signaling in the ventromedial hypothalamus regulates skeletal and metabolic homeostasis. Image adapted from respective paper in Nature Communications (2024)
下丘腦腹內側的促胰液素信號傳導調節骨骼和代謝穩態。(圖片修改自《自然通訊》 (2024)相關文章)

A team of researchers from The University of Hong Kong (HKU) has made a significant breakthrough in understanding how energy metabolism and bone homeostasis are regulated in mice, which could lead to novel treatments for obesity and osteoporosis. The study, led by Professor Billy CHOW from the School of Biological Sciences (SBS), Faculty of Science, Professor Kelvin YEUNG from the School of Clinical Medicine, LKS Faculty of Medicine, and Professor Will Wei QIAO from the Faculty of Dentistry, along with their colleagues, has been published in the top journal Nature Communications, with Dr Fengwei Zhang from SBS as the first author.

In their pioneering research, the team discover that the hormone secretin, found within the ventromedial hypothalamus (VMH) of the brain, plays a vital role in controlling both energy balance and bone density. This finding challenges the traditional view that secretin’s primary function is in the digestive system, showcasing its importance in the central nervous system.

Using advanced genetic techniques, the researchers manipulated secretin signaling in mice and observed

remarkable outcome. They found that disruptions to secretin pathways in the VMH led to increased appetite, metabolic dysfunctions, and significant bone density loss. Conversely, enhancing secretin signals in the same area increased bone mass without affecting body weight or appetite.

‘Our study opens new doors to treating metabolic and bone diseases. The ability to control appetite and bone density through the brain has significant implications for tackling obesity and osteoporosis,’ notes principal investigator Professor Chow.

Looking forward, this research provides new ideas for developing innovative therapies targeting the brain to regulate body metabolism and bone health. The team plans to further investigate the applicability of these findings to human physiology and potential drug development.

The University of Hong Kong is known for its interdisciplinary approach, and this research represents a close collaboration between the fields of neuroscience, endocrinology, and orthopedics. Details can be found at Nature Communications under the title ‘Secretin-dependent signals in the ventromedial hypothalamus regulate energy metabolism and bone homeostasis in mice’.

The journal paper can be accessed here: https://www.nature.com/articles/s41467-024-45436-3

More information about the team:
Professor Billy Chow and his research group: http://www.biosch.hku.hk/staff/bc/bc.html
Professor Kelvin Yeung and his research group: https://www.ortho.hku.hk/biography/yeung-wai-kwok-kelvin/
Professor Will Wei Qiao and his research group: https://facdent.hku.hk/about/staff-profile.php?shortname=drqiao

由香港大學 (港大) 理學院生物科學學院鄒國昌教授、李嘉誠醫學院臨床醫學學院楊偉國教授、牙醫學院喬威教授所率領的研究團隊,最近在瞭解小鼠能量代謝和骨穩態如何調節方面取得重大突破,有望為肥胖和骨質疏鬆症帶來新療法。該研究剛於頂級學術期刊《自然通訊》(Nature Communications)上發表,生物科學學院的張鳳偉博士為該文章第一作者。

該研究小組發現,在大腦腹內側下丘腦中發現的促胰液素信號在控制能量平衡和骨密度方面發揮著至關重要的作用。這一發現挑戰了促胰液素的主要功能是在消化系統中的傳統觀點,顯示了其在中樞神經系統中的重要性。

研究人員利用先進的遺傳技術操縱小鼠的促胰液素信號傳導,並觀察到了顯著的結果。 他們發現,腹內側下丘腦中促胰液素途徑的破壞會導致食欲增加、代謝功能障礙和骨密度顯著下降。 相反,增強同一區域的促胰液素信號會增加骨量,而不影響體重或食欲。

「我們的研究為治療代謝和骨骼疾病打開了新的大門。 通過大腦控制食欲和骨密度的能力對於解決肥胖和骨質疏鬆症具有重要意義。」首席研究員鄒教授指出。

展望未來,這項研究為開發針對大腦的創新療法來調節身體代謝和骨骼健康提供了新思路。 該團隊計畫進一步研究這些發現對人類生理學和潛在藥物開發的適用性。

香港大學以其跨學科方法而聞名,這項研究代表了神經科學、內分泌學和骨科領域之間的密切合作。 詳細資訊可以在《自然通訊》的標題「下丘腦腹內側分泌素依賴性信號調節小鼠能量代謝和骨穩態」下找到。論文連結請見於: https://www.nature.com/articles/s41467-024-45436-3

有關研究團隊更多資訊
鄒國昌教授及其研究小組:http://www.biosch.hku.hk/staff/bc/bc.html
楊偉國教授及其研究小組:https://www.ortho.hku.hk/biography/yeung-wai-kwok-kelvin/
喬威教授及其研究小組: https://facdent.hku.hk/about/staff-profile.php?shortname=drqiao

HKU and HKUST collaborate on DNA replication initiation, recognized as one of Top 10 Scientific Advances in China for 2023

A joint study revealing a new mechanism on DNA Replication Initiation, led by The Hong Kong University of Science and Technology (HKUST), The University of Hong Kong (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.

Organised by the National Natural Science Foundation of China, the “Top 10 Scientific Advances in China for 2023” is jointly hosted by the High Technology Research and Development Center and the Center for Science Communication and Achievement Transformation, with the support of five journals, namely China Basic Science, Science & Technology Review, Bulletin of the Chinese Academy of Sciences, Science Foundation in China, and Science Bulletin. These 10 advancements were judiciously selected by thousands of experts from the Chinese Academy of Sciences, Chinese Academy of Engineering, and other institutions. The objective is to promote frontier and innovative research progress in China and encourage more researchers to engage in basic research. By deepening public understanding, concern and support for science, the event also seeks to foster a national climate favourable to scientific exploration.

This prestigious accolade was awarded to the team that includes Prof. ZHAI Yuanliang, Assistant Professor from the HKU School of Biological Sciences, Prof. DANG Shangyu, Assistant Professor from HKUST Division of Life Science (LIFS), and Prof. TYE Bik-Kwoon, Senior Member of HKUST Institute for Advanced Study (IAS), in recognition of their groundbreaking discovery of a new mechanism of the human pre-replication complex (Pre-RC) in regulating DNA replication initiation. The atomic resolution structure of the human Pre-RC provides detailed critical information for devising novel and effective anticancer strategies with the ability to selectively kill cancer cells.

“This recognition is a great honour for our research team and shows that our work is highly respected in the scientific community,” said Prof. Zhai Yuanliang from HKU. “Our knowledge of how DNA is copied is still quite limited. While previous studies in a type of yeast have given us some insights, there’s still so much we don’t know about how this process happens in human cells. Since there’s still a lot to discover in this field, every new development in understanding how DNA is copied by our replication machines is a big step forward. The knowledge we gain from our research will not only deepen our understanding of the basic processes of life, but it may also provide important insights into diseases like cancer and help us find new ways to treat them.”

Prof. Dang Shangyu from HKUST said, “Enhancing the specificity of chemotherapy drugs has always been a crucial consideration in developing anticancer compounds. We are delighted that our research breakthrough has received national recognition. Notably, all of the project’s structural work, including cryo-sample preparation, cryo-EM data collection and processing, was conducted at the HKUST Biological Cryo-EM Center. We are immensely grateful to the Lo Kwee Seong (LKS) Foundation for their generous support in establishing this state-of-the-art facility at HKUST, which has already facilitated several breakthroughs and discoveries in our research since its establishment in 2019. We look forward to continuing our investigations in this field and forging new hopes for cancer treatment.”

Research Background

DNA is the blueprint of life. It is present in every cell. Its duplex structure in complementary notations informs how it is replicated. It must be first separated into single strands and copied precisely. The history of DNA replication study can be traced back to 1950s when Prof. Arthur KORNBERG discovered an enzyme system in Escherichia coli extracts, which ultimately earned him a Nobel Prize. However, due to the lack of high-resolution structures, progress in DNA replication research lagged behind those achieved in the study of other macro molecular machines, such as the ribosome or the RNA polymerase.

Professor Tye Bik-Kwoon, who has joined HKUST since 2011, overcome these hurdles initially by collaborating with the Peking University team led by Professor GAO Ning, as well as Prof. Zhai, who obtained his PhD from HKUST before becoming a HKUST-IAS junior fellow. Together they made a series of groundbreaking findings, including determining the cryo electron microscopy (cryo-EM) structures of the yeast MCM2-7 double hexamer (DH) and the yeast origin recognition complex, which were published in Nature in 2015 and 2018. These studies laid the foundation for the present work on the structure of the human pre-replication complex when the HKUST cryo-EM facility became available and when Prof. Dang joined HKUST in 2019.

As one of the Top 10 Scientific Advances in China for 2023, this research determined at 2.59 Å the cryo-EM structure of the human Pre-RC, which is formed by the loading of the MCM2-7 DH onto origin DNA. This structure provides a clear understanding of how the MCM2-7 complex destabilises DNA, leading to the initial unwinding of the DNA duplex precisely at the juncture of the two coupled MCM2-7 hexamers. Additionally, the team discovered that the MCM2-7 DH complexes are loaded onto DNA at numerous sites throughout the human genome. Importantly, these sites are mutually exclusive with loci of active transcription to minimise interference between DNA replication and transcription. Moreover, when the initial open structure is disrupted, the MCM2-7 DH complexes fail to assemble onto DNA, resulting in a complete suppression of DNA replication initiation. The study provides a detailed understanding of the high-resolution structure and mechanism of the human Pre-RC. This knowledge can be leveraged to develop non-toxic anticancer drugs in the future. The research was published in the top international scientific journal Cell in January, 2023. (click here for link)

About The University of Hong Kong

Founded in 1911, The University of Hong Kong (HKU)(www.hku.hk) is the first and oldest institution of higher education in Hong Kong. For over a century, the University has dedicated itself to creating knowledge, providing education, and serving society. Today, HKU has an established worldwide reputation for being a research-led comprehensive University with ten Faculties. HKU has a proud record of academic recognition in research through honours and awards received from both local and international bodies. The University strives to attract and nurture outstanding scholars through excellence and innovation in its research and knowledge exchange activities. Its research areas cover a wide range of issues with the aim of benefitting industries, businesses and the community. Regarded as Asia’s Global University, HKU brings together experts from diverse disciplines, partnering with prestigious universities and research institutes around the world. It has 51 academics named on the list of “Highly Cited Researchers 2023” from Clarivate, ranking 13th globally among all institutions. HKU is in pursuit of teaching and learning excellence in a broad range of disciplines and professions. With the holistic design of the curricula, along with award-winning teaching and learning resources and support, students at HKU can fully develop intellectual and personal strengths while gaining lifelong learning opportunities to contribute to the community.

About The Hong Kong University of Science and Technology

The Hong Kong University of Science and Technology (HKUST) (https://hkust.edu.hk/) is a world-class research intensive university that focuses on science, engineering and business as well as humanities and social science. HKUST offers an international campus, and a holistic and interdisciplinary pedagogy to nurture well-rounded graduates with global vision, a strong entrepreneurial spirit and innovative thinking. Over 80% of our research work were rated “Internationally excellent” or “world leading” in the Research Assessment Exercise 2020 of Hong Kong’s University Grants Committee. We were ranked 2nd in Times Higher Education’s Young University Rankings 2023, and our graduates were ranked 29th worldwide and among the best from universities from Asia in Global Employability University Ranking 2023. As of September 2023, HKUST members have founded 1,747 active start-ups, including 9 Unicorns and 13 exits (IPO or M&A), generating economic impact worth over HK$ 400 billion. InvestHK cited QS World University Rankings by Subject 2021 to demonstrate the performance of five world’s top 100 local universities in several innovation-centric areas, among which HKUST ranked top in four engineering and materials science subjects.

News Links: 1, 2, 3, 4, 5, 6

發現人體MCM2至MCM7蛋白複合體(Minichromosome Maintenance 2-7,微小染色體維持蛋白2-7)調控DNA複製起始的新機制。

香港大學聯同科技大學與其他研究所領導「DNA複製起始新機制研究」,有望應用於研發新型、高效並具針對性的抗癌藥物,從而能選擇性殺死癌細胞。研究獲選為去年「中國科學十大進展」,團隊認為過程為治療癌症提供新思路及方法,盼未來為人類健康及醫學發展作出更大貢獻。

港大生物科學學院助理教授翟元樑表示,是次獲選證明研究團隊獲科學界高度認可,但他認為科學家對DNA複製過程的認識仍不足,在這個領域上還有許多未知有待他們探索,故每個新發現都對科學有一大貢獻。他認為,透過研究DNA複製過程,不僅能深入地理解生命的基本過程,亦能為治療癌症等疾病提供新思路及方法,故希望未來能揭開DNA複製的神秘面紗,為人類健康及醫學發展作出更大貢獻。

科大生命科學部助理教授黨尚宇則表示,提高化療藥物作用的針對性一直是研發抗癌化合物的重要考量,對於研究獲國家肯定十分欣喜。他亦提到,團隊在科大生物冷凍電鏡中心進行所有與冷凍電鏡相關的工作,包括冷凍樣本製作、數據收集及處理,為研究帶來進一步突破及發現。他期望,未來繼續在此領域作進一步研究,譜寫癌症治療的新希望。

國家自然科學基金委員會主辦的「中國科學十大進展」旨在宣傳國內前沿及創新研究進展,從而激勵更多科研人員進行基礎研究,並加深公眾對科學的理解、關心及支持,營造良好的科學氛圍。

該研究於2023年1月發表在國際頂尖科學期刊《Cell》上。(點擊此處取得連結

新聞連結: 1, 2, 3, 4, 5, 6

We Are All Getting Fatter – Causes, Challenges and Solutions

Speaker:          Professor Chan Chi Bun

Associate Professor of Biological Sciences, HKU

Vice President, The Hong Kong Society of Endocrinology, Metabolism, and Reproduction

Date:               February 1, 2024 (Thursday)

Time:               5:30 pm – 6:30 pm (HKT)

Venue:             CYPP4, LG1/F, Chong Yuet Ming Physics Building, Main Campus, HKU

Registration:   https://bit.ly/combatobesity_reg

Abstract:

Obesity is a widespread metabolic disorder with increasing prevalence around the world. In Hong Kong, the incidence of obese adults in our population has surged from 21% in 2003 to 33% in 2022. Given the strong correlation between obesity and numerous diseases like stroke, heart attacks, diabetes, and even cancer, the increasing number of obese people could significantly strain our healthcare and economic system. From a biological perspective, obesity is caused by the imbalance between food intake and energy expenditure. Subsequently, the nutrient and energy metabolism in different tissues of the body are dysregulated, leading to abnormal intracellular signaling and functional impairments. Different pharmacological interventions or lifestyle modifications have been developed to rescue the imbalanced metabolism in obese people in the past decades, but these methods are also accompanied by undesirable side effects. Hence, developing effective methods to control the body weight of obese people is still a hot research area nowadays. This lecture will discuss various causes of obesity, its detrimental impact on human health, and the latest research on preventive or therapeutic methods to combat obesity.

This 2nd “World is Our Oysters (WOO)” symposium is called:

  • To demonstrate the newly designed oyster hatchery, and explain its operational protocol to various stakeholders;
  • To identify ways through which new oyster hatchery technologies could be integrated with national effort to develop sustainable oyster aquaculture for one health with global perspective; and
  • To discuss about the need, objectives and
    deliverables of the proposed “Oyster Aquaculture Alliance for One Health”.

Read more at hkuoyster.hk

|Program Detail

 

Ranges of North Pacific albatrosses. Red dots indicate sampling sites (Midway Island, Tern Island, and Torishima) of Phoebastria nigripes and/or P. immutabilis.

Abstract

Throughout the Plio-Pleistocene, climate change has impacted tropical marine ecosystems substantially, with even more severe impacts predicted in the Anthropocene. Although many studies have clarified demographic histories of seabirds in polar regions, the history of keystone seabirds of the tropics is unclear, despite the prominence of albatrosses (Diomedeidae, Procellariiformes) as the largest and most threatened group of oceanic seabirds. To understand the impact of climate change on tropical albatrosses, we investigated the evolutionary and demographic histories of all four North Pacific albatrosses and their prey using whole-genome analyses. We report a striking concordance in demographic histories among the four species, with a notable dip in effective population size at the beginning of the Pleistocene and a population expansion in the Last Glacial Period when sea levels were low, which resulted in increased potential coastal breeding sites. Abundance of the black-footed albatross dropped again during the Last Glacial Maximum, potentially linked to climate-driven loss of breeding sites and concordant genome-derived decreases in its major prey. We find very low genome-wide (π < 0.001) and adaptative genetic diversities across the albatrosses, with genes of the major histocompatibility complex close to monomorphic. We also identify recent selective sweeps at genes associated with hyperosmotic adaptation, longevity, and cognition and memory. Our study has shed light on the evolutionary and demographic histories of the largest tropical oceanic seabirds and provides evidence for their large population fluctuations and alarmingly low genetic diversities.

The journal paper, entitled “Whole-genome Analyses Reveal Past Population Fluctuations and Low Genetic Diversities of the North Pacific Albatrosses. Molecular Biology and Evolution, Volume 40, Issue 7, July 2023, msad155”, can be found at the following link: https://doi.org/10.1093/molbev/msad155

Structural analysis of sorghum stilbene O-methylase (SbSOMT). A. SbSOMT (pink) shows high global structural similarity to SbCOMT (blue). SbSOMT is a unique OMT in Sorghum spp. while COMT is a common and widespread OMT enzyme. B. Close-up view of the substrate binding pocket docked with piceatannol. In SbSOMT (pink) and SbCOMT (blue), the stilbene A-ring and B-ring are positioned close to a key catalytic residue (H267/H282), respectively, for O-methylation. Images adapted from Nature Communications, 2023, doi:10.1038/s41467-023-38908-5

Stilbenes are natural compounds found in various plants that have shown potential health benefits for humans, with a unique chemical structure consisting of two aromatic rings linked by a double bond. While resveratrol, found in grapes and red wine, is the most well-known stilbene, there has been increasing interest in other types of stilbenes that could offer additional health benefits.

O-methylated stilbenes, which are produced by introduction of a methyl group (-CH3) to a hydroxyl (-OH) group on the stilbene backbone, are promising compounds for research. Some plant species, such as sorghum and wild sugarcane, have been found to produce different types of O-methylated stilbenes in response to abiotic or biotic stress and may have greater potency and bioavailability than non-methylated stilbenes. This makes these plant species particularly interesting for research on the biosynthesis of O-methylated stilbenes and potential applications in developing functional foods, nutraceuticals, and pharmaceuticals. Recently, a research team led by Dr Clive LO from the School of Biological Sciences at The University of Hong Kong (HKU) collaborated with laboratories at the University of Queensland (UQ), Australia, and the HKU School of Biomedical Sciences (SBMS), as well as scientists in Mainland China and Japan, to discover a novel stilbene O-methylase (SbSOMT) in sorghum, an enzyme which is responsible for catalyzing the production of O-methylated stilbenes. The discovery offers a new avenue for producing O-methylated stilbenes in larger quantities and at lower costs, which could lead to the development of new functional foods, nutraceuticals, and pharmaceuticals that harness the potential health benefits of these compounds. The research findings have recently been published in Nature Communications.

Background

Stilbenes are natural compounds found in plants with promising nutraceutical properties, known to provide a range of health benefits such as anti-ageing, anti-neurodegeneration, anti-diabetes, and chemo-preventive properties. O-methylation is a chemical process that can significantly enhance the potency and bioavailability of stilbenes. However, the biosynthesis of O-methylated stilbenes has not been well-studied, and further research is needed to generate specific stilbene compounds.

The research team conducted a study that showed how sorghum and wild sugarcane could produce different types of O-methylated stilbenes, such as pinostilbene, pterostilbene and isorhapontigenin. They used advanced genetic techniques, including CRISPR-Cas9 mutagenesis and sorghum transformation, to identify the key enzyme, SbSOMT, that mediates the specific chemical modification of stilbene called 3,5-bis-O-methylation in sorghum. This modification affects the biological activity of the stilbene, including its antioxidant and antiinflammatory properties.

The team also conducted phylogenetic analysis to study the evolutionary relationships between different organisms, and found that SbSOMT is unique to Sorghum plants and originated from a group of related proteins called caffeic acid O-methyltransferases (COMTs) commonly found in all other grasses. In addition, the team presented the first crystal structure for SbSOMT in collaboration with HKU SBMS protein structural biologists.

Research Significance

The researchers discovered that SbSOMT uses a chemical reaction similar to COMTs in the grass family, but it binds to the stilbene molecule differently. This different binding mode allows SbSOMT to modify the stilbene molecule in a specific way that produces different types of O-methylated stilbenes in sorghum. These different types of stilbenes are characterized by the location of the O-methyl group on the stilbene molecule, either on the A-ring or the B-ring.

In sorghum, SbSOMT modifies stilbenes in a way that produces A-ring O-methylated stilbenes, such as pinostilbene and pterostilbene. Meanwhile, wild sugarcane uses a common COMT enzyme to modify stilbenes to produce B-ring O-methylated stilbenes, such as isorhapontigenin. The difference between the Aring and B-ring O-methylated stilbenes is due to the specific way that SbSOMT interacts with the stilbene molecule, which involves the hydrophobic Ile144 and Phe337 residues in the SbSOMT enzyme. The research has found that sorghum and wild sugarcane can potentially be used to produce O-methylated stilbenes. These compounds have health benefits and can be used in nutraceuticals (which are like dietary supplements). The team also discovered the enzymes responsible for producing these compounds in these plants.

Their findings suggest that we could use molecular breeding and transgenic approaches to create specific types of O-methylated stilbenes with even more health benefits. This could open up new possibilities for creating healthier food and supplement options.

This research was supported by the Hong Kong Research Grants Council.
The HKU Libraries Open Access Author Fund provided support for the publication.
The journal paper, entitled “Regioselective stilbene O-methylations in Saccharinae grasses. Nat. Commun 14, 3462 (2023)”, can be found at the following link: https://doi.org/10.1038/s41467-023-38908-5

「白藜蘆醇」近年被廣泛應用於保健品和膳食補充劑,屬於二苯乙烯類化合物 (Stilbenes),可在特定植物找到,具抗氧化、抗炎、降血脂、保護心血管及抗癌等功效。港大生物科學學院副教授盧思聰率領的研究團隊,與澳洲昆士蘭大學、港大生物醫學學院及來自中國內地和日本的科學家合作,在高粱發現一種名為二苯乙烯O-甲基化的新型酶(SbSOMT),可合成O-甲基化二苯乙烯類化合物,有望為研發以更低成本生產該類化合物提出新方向,推動其功能性食品、營養保健品和藥品的開發和發展。

團隊發現高粱和野生甘蔗可產生多種不同種類的O-甲基化二苯乙烯類化合物,包括松茋、紫檀芪和異丹葉大黃素,並使用先進基因編輯技術CRISPR-Cas9,包括誘變和高粱轉化,找到一種新型酶SbSOMT。研究小組同時做了進化樹分析,發現SbSOMT是高粱特有的酶,源於一組普遍存在於禾本科植物的蛋白質。研究獲研究資助局資助,成果最近於學術期刊《自然—通訊》發表。

News links: 1, 2, 3

Our undergraduate alumna, Rachel Wai Ching CHU, who majored in Ecology & Biodiversity and graduated in 2019, began investigating methane seepage during her final year of undergraduate studies at the School of Biological Sciences as part of the capstone requirement for her major.Under the supervision of Dr Moriaki YASUHARA from the School of Biological Sciences and The Swire Institute of Marine Science, this research has recently been published in the highly respected and prestigious peer-reviewed scientific journal Geology. The article, titled ‘Late Quaternary paleoceanography of Vestnesa Ridge, Fram Strait: Ostracode species as a potential indicator of cold seep activity’, explores the topic of methane seepage and its potential indicators. Geology has been published by the Geological Society of America since 1973 and is a leading journal in the field of earth science.

An investigation on how Methane levels impact our environment

Methane is a potent greenhouse gas and is often portrayed as a significant contributor to global warming and climate change. A large quantity of methane is trapped in the deep ocean under high pressure and low temperature. At different times throughout geological history, part of it was released into the water and then into the atmosphere, thereby changing the climate.

The release of methane is called methane seepage. Rachel’s paper investigates the strength of methane seepage activities in the Vestnesa Ridge during the Late Quaternary using two paleo-proxies: ostracod assemblages and carbon isotopes in foraminifera.

Ostracods and foraminifera are two sand-grain-sized animals used by palaeontologists as micro-fossils to study environmental changes in the past. The paper suggests that one of the ostracod species found, Rosaliella svalbardensis, to be an indicator of moderate methane release since it was only present during moderate methane release, absent when there is no methane release or the activity is too strong. By discovering a reliable proxy for methane seepage activities, researchers can learn more about past seepage activities and their impacts on climate and the ecosystem.

From FYP to Published Research

Moriaki and his team specialise in palaeontology, and Rachel started volunteering in the Yasuhara Lab during the summer of her second year of undergraduate studies. Her involvement continued until her graduation and the research on methane seepage began as her final year project as part of the capstone requirement for her major. This career-oriented capstone course is designed for students interested in pursuing a career in academia. It imitates the academic environment and requires students to complete a research project of their choosing under the supervision of one of the topmost professors at The University of Hong Kong.

Rachel described the entire experience as transformative, she said, ‘Paleo-related studies are rare in Hong Kong, and our curriculum did not cover much about it. Therefore, I owe everything I know in this field to Moriaki and his team, who tirelessly taught me from the very basics. Rachel said the capstone course provided her with an opportunity to experience a research project from start to finish, ‘No matter how fancy or detailed the lectures are, they cannot compete with hands-on experience, from wet-sieving the samples and identifying the species to analysing the data and coming up with a paper. Without these valuable experiences, I would have never known about the existence of this often overlooked yet the wonderful field of palaeontology, let alone pursuing an MPhil in this area now.’

Visit the Yasuhara Lab’s website here.

Click here to learn more about HKU BSc Ecology & Biodiversity Major.

Journal Title: ‘Late Quaternary paleoceanography of Vestnesa Ridge, Fram Strait: Ostracode species as a potential indicator of cold seep activity (Geology, 2023)’

The journal paper can be accessed here.