研究与创新 |
HKUST and PolyU researchers develop an in-vitro vesicle formation assay to reveal mechanistic insights into the secretory pathway

(This article was originally published on EurekAlert! on September 7, 2021)

 

Scientists from The Hong Kong University of Science and Technology (HKUST) and The Hong Kong Polytechnic University (PolyU) have developed an in-vitro vesicle formation assay, shedding light on cargo clients and factors that mediate vesicular trafficking and providing a robust tool to offer novel insights into the secretory pathway.

The secretory pathway is a very important process that takes place in human cells. Many growth factors, hormones and other important factors in the human body are secreted from cells through the secretory pathway to perform their physiological functions. In addition, many newly synthesized proteins must be transported to specific subcellular localization through the secretory pathways to perform their functions. In the secretory transport pathway, transport vesicles function as vehicles to carry cargo molecules. Similar to logistics and delivery services in our daily lives, the transportation of cargo molecules to the correct target sites depends on whether the cargo molecules are accurately sorted into specific transport vesicles. Defects in cargo sorting would induce defects in establishing cell polarity, immunity, as well as other physiological processes.

The key players that mediate protein sorting in the secretory pathway include small GTPases of the Arf family and cargo adaptors. The Arf family GTPases cycle between a GDP-bound inactive state and a GTP-bound active state. Upon GTP binding, Arf proteins mediate membrane recruitment of various cytosolic cargo adaptors. Once recruited onto the membranes, these cargo adaptors recognize sorting motifs on the cargo proteins to package cargo proteins into vesicles.

Although significant progress has been achieved in understanding the general steps of cargo sorting, the spectrum of cargo clients of a specific Arf family member or cargo adaptors remains largely unexplored. Led by Prof. GUO Yusong, Associate Professor of Division of Life Science at HKUST and Prof. YAO Zhongping from PolyU, the research team used an in-vitro assay that reconstitutes packaging of human cargo proteins into vesicles to quantify cargo capture. Quantitative mass spectrometry analyses of the isolated vesicles revealed cytosolic proteins that are associated with vesicle membranes in a GTP-dependent manner. One of them, FAM84B interacts with cargo adaptors and regulates transport of transmembrane cargo proteins. In addition, they uncovered novel cargo proteins that depend on GTP hydrolysis to be captured into vesicles.

Then they utilized this assay and identified cytosolic proteins that depend on a specific Arf family protein, SAR1A, to be recruited to vesicle membranes. One of the cytosolic protein, PRRC1, is recruited to endoplasmic reticulum (ER) exit sites, and interacts with the inner COPII coat. Its absence increases membrane association of COPII and affects ER-to-Golgi trafficking.

Utilizing this assay, they also identified the clients of COPII vesicles. These clients include two cargo receptors, SURF4 and ERGIC53. Through analyzing the protein composition of vesicles isolated from control cells or cells depleted of SURF4 or ERGIC53, they revealed specific clients of each of these two cargo receptors.

These results indicate that the vesicle formation assay in combination with quantitative mass spectrometry analysis is a robust and powerful tool to systematically reveal cargo proteins that depend on a specific factor to be packaged into vesicles, to analyze protein profiling of transport vesicles under different physiological conditions, and to uncover cytosolic proteins that interact with a specific factor on vesicle membranes.

This study was recently published in Proceedings of the National Academy of Sciences.

Prof. Guo’s research team focuses on investigating molecular mechanisms regulating protein sorting in the secretory pathway. Dr. HUANG Yan (a postdoctoral research associate from Prof. Guo’s lab at HKUST), Dr. YIN Haidi from PolyU and Dr. LI Baiying from CUHK are co-first authors of this study. Mr. LIU Yang, Dr. TANG Xiao, Miss WANG Wo and Miss WU Zhixiao from the Guo lab also participated in this study.

研究与创新 |
科大研发宽禁带半导体氮化镓基互补型逻辑电路 拓宽氮化镓电子学的疆界

香港科技大学(科大)电子与计算机系陈敬教授带领其团队,为方兴未艾的氮化镓(GaN)基电子学研究引入重要的新成员——互补型逻辑电路。相关技术的成功实现大幅拓展了相关研究领域的疆界,有望使氮化镓基电子器件及相关集成电路的功能与性能得到进一步提升,从而更具竞争力。


氮化镓基电子器件已历逾25年的研发,近年来亦开启了快速商业化的进程,并现身于如5G无线通信基站、移动设备的小型快速充电器、激光雷达等应用场景。在不久的将来,能够提供极高效率与功率密度的基于氮化镓的功率转换、电源管理系统有望被应用于诸多涌现中的新型应用,如数据中心、无人驾驶、电动汽车、无人机、机器人等。所有这些应用既相当耗电,又需要供电模块尽可能紧凑,这恰是氮化镓基功率电子产品相对于传统硅基半导体产品的优势所在。为了充分发掘氮化镓的潜能,获得更为智能、稳定、可靠的电源系统,学界与业界在过去十余年间一直在寻找、开发合适的技术平台以实现功率开关和各个外围功能模块的高度集成。其中,逻辑电路在为外围电路中广泛存在,并扮演重要角色。


占据当今半导体产业的统治地位硅基微电子与集成电路的经验表明,互补型逻辑电路是制备大规模集成电路的最优拓扑。“互补(C)”,意味着电路由两种具有相反控制逻辑的晶体管组成,一类拥有n型导电沟道,另一类则是p型沟道。因为主流硅基互补型电路中的晶体管栅极为金属(M)-氧化物(O)-半导体(S)结构,所以更广为人知的名称是“CMOS”。这样的拓扑可以带来诸多好处,其中最引人注目的是它极低的静态功耗。因为控制逻辑相反,所以在任何一个逻辑状态下,总有一类器件处于关断状态,从而有效阻断电流、显著降低功耗。然而,由于高性能p沟道氮化镓晶体管不易获得,与n沟道器件的集成亦困难重重,基于氮化镓的互补型逻辑电路的研发进展缓慢。


陈教授的团队基于一个面向氮化镓功率应用的商用平台上,开发了一种新型的方案,有效解决了p沟道器件实现过程中至关重要的一个问题:栅极介质层与p沟道之间不理想的界面让本已不高的空穴迁移率进一步降低。他们在科大的实验室自主开发了一种氧等离子体处理技术,以此为依托制备了一种具有“埋层沟道”的p型器件结构,从而令这一新型的氮化镓基p沟道器件在一系列关键性能之间取得了良好的平衡,包括实现增强型的阈值电压、高开关电流比、高电流驱动能力。团队更进一步着手开发同片集成技术——在同一个半导体芯片上同时制备n沟道与p沟道氮化镓晶体管,并通过合适的片上互联构建基于氮化镓的互补型逻辑电路且与该平台上的功率器件集成。


该团队首次以互补型电路拓扑实现了基于氮化镓的所有基本逻辑门电路,包括非门、与非门、或非门,也实现了传输门。他们更进一步展示了可以工作在兆赫兹频率的多级集成逻辑电路。陈教授告诉我们:“这是一次鼓舞人心的飞跃。我们首先证明了所有的基本单元都能实现,然后证明了这些基本单元可以被组合起来。所以,理论上讲所有的氮化镓基互补型逻辑电路都可以得到了,只需要适当地组合这些基本逻辑门。”


电路设计者可以开始搭建更加强大、精巧、复杂的氮化镓基集成电路,包括但不限于:1)具有更先进的片上控制、传感、保护、驱动能力的高效节能的功率集成电路;2)极端环境下(如汽车与航空系统)的计算与控制电路。在不远的未来,基于氮化镓的计算芯片或许可以实现并在特定场景中发挥作用,例如用于诸如行星探索甚至深空探索等关键任务。


该工作的器件技术在科大清水湾校区的纳米系统制备实验所(NFF)制备。该工作为香港研资局的研究影响基金(Research Impact Fund)所支持,并新近得到深圳市科技创新委员会深港澳科技计划的支持。该工作发表于近期在《自然 · 电子学》期刊上。


全文链接:https://www.nature.com/articles/s41928-021-00611-y


可分享链接(未订阅《自然 · 电子学》期刊的读者亦可查阅文章)https://rdcu.be/cpbR3

研究与创新 |
HKUST researchers develop a photo-rechargeable lead-free perovskite lithium-ion battery that generates energy and stores battery on a single device

A team of researchers from the Hong Kong University of Science and Technology (HKUST) has developed an inexpensive, lightweight, and non-toxic (lead-free) photo-battery that has dual functions in harvesting solar energy and storing energy on a single device, making it possible to charge a battery under the sun, without having to plug the device into the wall.

The increasing demand for sustainable energy sources has driven a surge of interest in solar energy and developing storage devices for it. One such device, the photo-battery, is capable of both generating and storing energy in a single device architecture. In theory, this design should permit increased energy storage efficiency and energy density, while decreasing ohmic losses, relaxing packaging requirements and thus reducing the weight, the bulk, and the cost of the system.  In reality, however, the poor interface between materials tends to create problems with charge transport, greatly reducing the efficiency in comparison to the simple system of a solar cell wired to an external battery.  

A team led by Prof. Jonathan Eugene HALPERT, Assistant Professor from the Department of Chemistry at HKUST, has made advancements towards developing more efficient photobatteries by expanding the utility of a class of materials known as perovskite, which has had applications in solar cells and most recently in batteries.  The perovskite halide the team developed acts as a photoelectrode that can harvest energy under illumination without the assistance of an external load in a lithium-ion battery, and is in stark contrast with its existing counterpart for it does not contain lead, hence it has higher stability in air and is free from the concerns of lead poisoning. For their research, the team has replaced lead with bismuth (Bi), a non-toxic element, and forming a strongly light-absorbing crystalline material.

The lithium-ion battery works by allowing electrons to move from a high energy state to a lower one, while doing work in an external circuit.  The photobattery has a mechanism similar to an ordinary battery except that it need not be supplied current or plugged into the wall to be charged electrically, but can be charged photoelectrically under the sun.  The active material in this new battery is the lead-free perovskite which, when put under light, absorbs a photon and generates a pair of charges, known as an electron and a hole.  The team conducted chrono-amperometry experiments under light and in dark to analyze the increase in charging current caused by the light, and recorded a photo-conversion efficiency rate of 0.428% on photocharging the battery after the first discharge.  The next step of the team is to experiment with different materials for better performance and efficiency, so that the photobattery can be commercialized in the market.

“At present, we plug all our appliances into the wall to charge them. With further development in this field of photobatteries, we might not have to plug them in at all in the future,” said Prof. Halpert.  “We might be able to harvest solar energy and use it to fulfil the power requirements of any devices with modest power needs.  Our work is one of the initial steps taken in this field, and, of course, a lot of improvements will be needed to achieve better performance, but we are confident that we can improve its stability and average efficiency with further refinement.”

This photobattery can serve as the built-in battery for devices such as smartphones or tablets, and even remote energy storage applications, which can be made easy with these photobatteries for they are lightweight and portable.  It should also help lower production cost when compared to a system consisting of a solar cell plus an external battery since only the battery part is required.

This study was recently published in the scientific journal Nano Letters on June 16.

研究与创新 |
HKUST Researchers Unveil a Non-classical Nucleation Process That Enhances Ice Formation on Surfaces

(This article was published on EurekAlert! on August 17, 2021)

 

Scientists from the Hong Kong University of Science and Technology (HKUST) have recently discovered a non-classical nucleation process that can greatly facilitate ice formation on foreign surfaces. This finding lays the foundation to predict and control crystallization processes.

Ice is omnipresent and profoundly impacts our daily life, influencing areas such as climate change, transportation, and energy consumption. Understanding the process of ice formation can decelerate the rate at which glaciers melt and sea levels rise and alleviate other major environmental concerns. Since ice formation is mainly governed by ice nucleation followed by the growth of the nuclei, scientists have put in a great effort to understand the thermodynamics and kinetics behind the nucleation processes. Ice nucleation can occur in two distinctive ways: homogeneously in bulk water or heterogeneously on the surface of a solid material, where heterogeneous ice nucleation (HIN) is the predominant mode of ice formation on earth. However, unlike homogeneous ice nucleation, the water-surface interactions present in HIN make the nucleation process sensitive to surface properties. Understanding how surfaces impact the nucleation process is a promising approach to better predict and control crystallization processes. 

A common model used to quantify nucleation kinetics based on a thermodynamic framework, classical nucleation theory (CNT), suggests that water molecules must form an ice nucleus of critical size before a crystallization process occurs. The formation of the critical ice nucleus is associated with a single free energy barrier, which needs to be overcome to trigger further ice growth. However, over the years, both experiments and simulations have revealed that CNT is often insufficient to describe some complex nucleation processes. Consequently, CNT has been a subject of immense debate, and non-classical nucleation theories have been alternatively proposed. 

Different from CNT, which is based on overcoming a single free energy barrier, non-classical nucleation theories suggest that nucleation processes consist of two or more steps separated by multiple free energy barriers. Although non-classical nucleation theories may be a more sustainable model, the atomistic mechanisms and structural evolutions during nucleus formation in non-classical nucleation pathways are not well known; and remains a challenge for experimental techniques to unravel.

Now, for the first time, a group of researchers at HKUST led by Prof. Xuhui Huang from the Department of Chemistry combined Markov State Models (MSMs) – which model long-timescale dynamics of chemical molecules - and transition path theory (TPT) – which describes the reaction pathway of rare events - to elucidate the ensemble pathways of HIN. MSMs identify intermediate states of disordered ice mixtures and compare parallel pathways (classical vs. non-classical). This advantage helped unravel the underlying mechanisms of non-classical nucleation processes and the co-existence of the two pathways.

These researchers show that the disordered mixing of ice stabilises the critical nucleus and makes the non-classical nucleation pathway as accessible as the classical pathway, whose critical nucleus mainly consists of potential energy-favoured ice. They also discovered that at elevated temperatures, the nucleation process prefers to proceed via the classical pathway since the potential energy contributions, which favour the classical pathway, prevail. 

“Not only does our work uncover the mechanisms of non-classical nucleation processes, but it also demonstrates how the combination of MSMs and TPT offers a powerful framework to study structural evolutions of ice nucleation processes,” said Prof. Huang. “More importantly, this method can be extended to other crystal nucleation processes that are challenging to study, which will open new doors for scientists attempting to predict and control crystallization processes.”

The findings were recently published in the scientific journal Nature Communications. The first author of this work: Dr. Chu Li is a long-time HKUST affiliate who completed his PhD, and currently conducts his post-doctoral training at HKUST. 

研究与创新 |
HKUST Scientists Develop Genome-editing Strategy for Potential Alzheimer’s Disease Therapy

An international research team led by scientists from the Hong Kong University of Science and Technology (HKUST) has developed a novel strategy using brain-wide genome-editing technology that can reduce Alzheimer’s disease (AD) pathologies in genetically modified AD mouse models. This advanced technology offers immense potential to be translated as a novel long-acting therapeutic treatment for AD patients.

In China alone, over 500,000 patients are estimated to be living with a hereditary form of AD - familial Alzheimer’s disease (FAD), which is a congenital form of AD highly associated with family history. Although FAD has a clear genetic cause and can be diagnosed before cognitive problems occur, no effective treatment currently exists.

There is enormous potential in the use of genome-editing technology1 as therapeutic strategies for diseases caused by inherited mutations, such as FAD. It is especially useful for correcting disease-causing genetic mutations before symptoms appear, for which it is considered a “once-and-for-all” treatment as its effects can last a lifetime. However, several hurdles have prevented its clinical development and application - most notably the lack of an effective, efficient, and non-invasive means to deliver genome-editing agents into the brain. Furthermore, existing genome-editing technologies are unable to generate beneficial outcomes throughout the whole brain.

Recently, a team led by Prof. Nancy Ip, Vice-President for Research and Development at HKUST, developed a new genome-editing system that not only crosses the blood–brain barrier, but also delivers an optimized genome-editing tool to the entire brain. Using a newly engineered delivery vehicle for genome-editing, this strategy achieves efficient brain-wide genome editing through a single non-invasive intravenous administration. This effectively disrupts FAD-inflicted mutations in AD mouse models and ameliorates AD pathologies throughout the entire brain, paving the way to novel therapeutic development for the disease.

Meanwhile, the research team also found in the mouse models that the level of amyloid, a protein thought to drive neurodegeneration in AD, remained low for 6 months post-treatment (about 1/3 of their normal lifespan), demonstrating that this single-shot genome-editing strategy has lasting effects. More importantly, no side effects were detected so far in the mice. 

“As the first demonstration of efficient brain-wide genome editing to alleviate Alzheimer’s disease pathology throughout the whole brain, this is really an exciting development,” said Prof. Ip, who is also the Morningside Professor of Life Science and Director of the State Key Laboratory of Molecular Neuroscience at HKUST. “Our work is an important milestone for the use of genome editing in treating hereditary brain diseases, and contributes to the development of precision medicine for inherited forms of neurodegenerative diseases.”
 


Genome editing of the familial mutation in AD mice improves their memory performance.


This research was a collaborative effort among scientists from HKUST; the California Institute of Technology; and the Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences. The results were recently published in Nature Biomedical Engineering

 

1Genome editing is a technology that precisely modifies a living organism’s genomic DNA by deleting, inserting, or replacing the DNA at specific locations of the genome.

领袖思维 |
专家系列:探索最暗黑之谜

六十年前,人类首度踏足太空,震撼世界;多年来,数以百计的太空探索任务不断出现,人类得以对宇宙加深认识和瞭解。在科学家希望解开的芸芸太空疑团中,黑洞为最扑朔迷离、引人入胜的天文现象,我们对它的认识十分有限。

经过数十年努力,科学家终于在2019年首次摄得黑洞真貌,本年初再下一城,得到一张影像更细緻的照片,为黑洞研究写下重要里程碑。这些划时代的影像证明了在距离地球约5,400万光年的M87星系中心,存在一个相等于65亿个太阳的超大质量黑洞。

 

 

爱因斯坦理论又赢了
数年前,天文学家对黑洞的看法跟现在截然不同。科大物理学系副教授王一指出:「假如你问当时的天文学家,是否可能存在质量相等于太阳100倍的黑洞,他们会告诉你这并不存在。可是,我们现正切切实实地发现了它!」

成功拍摄这神秘天体的影像,为物理学带来新的启示,有助我们从多方面加深瞭解黑洞。王教授说:「多年来,一直有不同理论描述黑洞视界附近的强引力,但这张照片证明了爱因斯坦的广义相对论再次获胜。照片显示的情况,跟他一百年前的预测分毫不差!」黑洞阴影的形状,更加印证了爱因斯坦的理论。

照片中的影像亦有助瞭解黑洞结构的形成和行为,如吸引物质落入黑洞的吸积盘,以及垂直于物质盘的等离子射流 。王教授说:「照片加深了我们对喷流物理学的认识。」

 

「另一只眼睛」看宇宙
除了黑洞,科学家也在研究爱因斯坦所预测的引力波,即两个天体(如行星或恆星)相互环绕运行而形成的时空涟漪。人类在2015年首次观察到因两个黑洞合併而出现的同类事件。王教授解释:「这是观察宇宙的一个崭新和独立途径。从前,我们只研究电磁波(即光),现在却开启了引力波天文学的新纪元。

「就像从前我们只用一只眼睛看宇宙,有了引力波,另一只眼睛也张开了!」

长久以来,科学家总觉得捕捉黑洞影像是遥不可及的事情,因为需要解像度极高的镜头才能做到。情况就像站在月球上的太空人,可以看见你在地球吃饭时碟上的餸菜。

王教授说:「观测远方的事物,你需要使用解像度高的望远镜。望远镜的镜头或光圈越大,採光能力越强,解像度也越高。以拍摄黑洞来说,我们需要像地球一样大的镜头。」

那么,究竟「不可能的任务」是如何达成的?这得归功于一项研究多年、能连结地球上不同望远镜的技术,使它们能有效地形成一口径等同地球大小的虚拟望远镜。

你或许会问,研究一些与地球距离如此遥远的东西,重要之处在哪?王教授说,照片中的影像有助科学家获得远超黑洞的知识,触类旁通,如瞭解星系怎样形成,超新星爆炸,以至解答「我们从哪里来」这个根本问题。

 

基础物理学的价值
王教授续说,认识这些天体是驱动科技发展的强大力量。要探索科学未为人知的一面 —无论大如宇宙,抑或小如基本粒子,都需要倚仗尖端科技。因此,探索基础科学可以推动科技发展。

王教授是高能物理学理论及宇宙学专家,2007至今,已发表超过90篇以基础物理学为重点的论文。最近,他埋首研究黑洞脉冲星系统,瞭解这种系统有助我们探索物质的极端状态﹔另外,他也在研究早期宇宙,思考大爆炸后发生了甚么事情?宇宙的命运又会怎样?

放眼未来,才可凸显基础科学的价值。王教授说:「我们约100年前已发现量子力学,那时候可没人懂得这门科学的用处,但到了今时今日,半导体理论已成为计算机技术的基石,其实就是量子力学当中有关凝聚态能量带的研究结果。」

「我们可能要等 100 年或更长时间才看到研究的影响力!但在等上100年之前,我们可以先理解事物运作的根本原理,即使我们还不清楚如何应用,这点十分重要。」

 

好奇心是进步的原动力
不少学生修读过王教授的现代物理学课程,都受到老师的好奇心所触动。 

他说:「我衷心希望所有学生都对科学充满好奇,而不是只关心考试和功课。我的心愿就是学生主动求知,乐意在每晚睡前思考事物运作的方式!」

研究与创新 |
科大研究团队解开无肠深海管虫的基因组秘密

为制造生物材料和营养互补等应用带来研究新方向

 

香港科技大学(科大)的研究人员首次破解无肠深海管虫的染色体层面基因组,发现了管虫如何透过其共生细菌为其制造的有机营养物,令牠得以于极端环境中生存的机制。有关研究为制造生物材料及抑制微生物繁殖等应用范畴提供基础。

深海管虫是深海海底热泉(hydrothermal vent)和冷泉(cold seep) 这种黑暗、高压并经常含有高浓度有毒物质生态环境的常见生物,它们之所以能于此等极端环境中生存兼迅速生长的原因,实有赖于存活在牠们体内、一种能让硫化物氧化的细菌。不过,由于缺乏基因组的数据,这段互补「联姻」的成功一直是一个谜。

现在,由科大海洋科学系讲座教授暨系主任钱培元及香港浸会大学生物系教授邱建文共同带领的研究团队,从南中国海水深约1,400米的海底冷泉区成功采集深海管虫样本,并对深海管虫及其共生细菌的基因组进行测序组装和分析,探究两者成功建立共生关系背后的基因组特征。

透过基因组学、转录组学和蛋白组学分析,研究团队发现共生细菌适应性强,能将多种包括硫代硫酸盐、一氧化碳和氢气等化学物质转化为能源。

身兼科大捷成David von Hansemann 理学教授的钱教授表示:「该细菌拥有完整的新陈代谢途径,为管虫输出营养,包括碳水化合物、氨基酸和维生素/辅因子等生物化合物。」研究团队亦发现细菌为求与深海管虫共生,演化出能分散宿主免疫系统注意力的策略,以逃避其防御机制。与此同时,深海管虫的基因组亦出现了改变以促进这个共生过程。管虫不但会制造一种酶去消化这个细菌以获取营养,更拥有一个可以控制细胞死亡的路径,以确保细菌数量维持在对自己最有利的水平。

为了解让管虫得以从海底获取无机物、被称为「几丁质管」这独特结构的形成机制,团队进一步分析了管虫坚韧的几丁质管的蛋白质,发现了 35 种几丁质管基质蛋白,包括合成几丁质微纤维并将其分泌到细胞外基质的聚合酶、聚合几丁质并为有机基质提供聚合物框架的几丁质结合蛋白,以及能增强管韧性及重塑几丁质支架的的蛋白质。

钱教授补充谓:「我们的研究发现为不同应用范畴带来新方向,如开发补充营养策略或抑制微生物繁洐的新方法等。而深海管虫所制造的酶,亦可能发展成一种新的生物材料。」

研究结果已于国际学术期刊Molecular Biology and EvolutionThe ISME Journal发表。

大学公告 |
School of Science offers 2020 Admission figures for JUPAS applicants to make reference to HKUST’s Science programs

JUPAS Admission Scores – 2020 intake


 

Admission Requirements and Admission Score (IRE) (For 2021 intake)


Admission Requirements and Admission Score (SSCI‐A / SSCI‐A (AI) / SSCI‐B) (For 2021 intake)

 

JUPAS score calculation for SSCI‐A, SSCI‐A (AI) and SSCI‐B

 

List of majors for SSCI‐A, SSCI‐B and SSCI‐A (AI) students

 

Admission Requirements (BIBU and MAEC) (For 2021 intake)

 

JUPAS score calculation for BIBU (JS5811) and MAEC (JS5813) (For 2021 intake)

 

Scholarship Schemes (For 2021 intake)

 

Click here to view the full version. 

大学公告 |
HKUST School of Science 2021 JUPAS Program Consultation – Events at a glance

2021 JUPAS Program Consultation (IRE Program) – 5 Jul 2021

 

Slideshow of IRE event at a glance

 

IRE Program Talk

 

Video of IRE student sharing 

William YAM (JUPAS, Class of 2020)

 

Research lab tours guided by IRE students

IRE-LIFS

 

IRE-PHYS

 

2021 JUPAS Program Consultation (BIBU Program) – 7 Jul 2021

Slideshow of BIBU event at a glance

 

BIBU Program Talk

 

Video of BIBU student sharing
Sonia LO (JUPAS, Class of 2021)

 

Thomas Michael BIEK (Local DE, Class of 2021)

 

2021 JUPAS Program Consultation (MAEC Program) – 9 Jul 2021

Slideshow of MAEC event at a glance

 

MAEC Program Talk

 

Video of MAEC student sharing
LEE Yat Long Luca (JUPAS, Class of 2020)

 

HO Pak Wa Monoceros (JUPAS, Class of 2020) 

 

2021 JUPAS Program Consultation (SSCI Programs) – 12 & 14 Jul 2021

Slideshow of SSCI events at a glance

SSCI-A

 

SSCI-B

 

SSCI Program Talk

 

School of Science Academic Advising and Support

 

Video of SSCI student sharing

Video of MATH student sharing
Yuki CHAN (JUPAS, Class of 2020)

 

Video of BIOT student sharing
Sze CHEUNG (JUPAS, Class of 2020)

研究与创新 |
科大研发简单血液测试 及早检测阿尔兹海默症

由香港科技大学(科大)领导的一支国际研究团队,成功利用中国人群患者数据,研发出首个简单而可靠的血液检测方法,能及早筛查并识别阿尔兹海默症(AD)患者,准确率逾 96%。

目前医生对于AD患者的诊断主要依靠对患者认知能力的测试,至于就AD病情的病理评估,最常使用的医疗程序是以脑部成像和腰椎刺穿术来侦测由AD引起的大脑病变。但有关方法费用昂贵、具侵入性,亦未有于世界各地获广泛应用。

现在,由科大副校长(研究及发展)叶玉如教授领导的研究团队,从 429 种与 AD相关的血浆蛋白中,识别出19 种具有AD患病特征的血浆蛋白生物标志物组群。团队根据这组标志物,设计了一套评分系统,可将 AD 患者自健康人群中区分出来,其准确率超过 96%。该系统还能辨别AD早、中及晚期三个阶段,可用作监测患者的病情发展。

身兼科大晨兴生命科学教授及分子神经科学国家重点实验室主任的叶教授表示:「基于先进的超灵敏血液蛋白检测技术,我们成功开发了这套简单、无创而精准的 AD 诊断方法,将为AD的大规模筛查及分期诊断提供重大助力。」

这项研究由科大与伦敦大学学院研究团队,以及来自包括威尔士亲王医院和伊利沙伯医院等本地医院的临床医生合作进行。团队利用尖端的超灵敏高通量邻近延伸分析技术 (PEA),从香港 AD 患者所收集的血浆样本当中,检测了逾 1,000 种蛋白质的水平变化情况,从而取得是次研究成果。

这项令人振奋的发现令高效的AD血液检测技术得以诞生,并为开创新型AD治疗方法打下基础。作为迄今为止就 AD 患者血液蛋白方面最全面的研究,有关结果近日被国际权威科学期刊Alzheimer's & Dementia: The Journal of the Alzheimer's Association刊载,并在不同AD 研究和学术交流平台,包括Alzforum,获得热烈的关注和讨论。

据统计,全球罹患AD的人口数目已超过 5,000万。患者会丧失脑细胞,并岀现一系列脑功能及认知功能障碍,包括丧失记忆,以及出现行动、推理和判断能力受损等症状。然而,尽管AD 早在症状出现前至少10-20 年已对患者大脑产生显著影响,患者却往往只在记忆出现问题时,才会寻求医生诊治。

研究与创新 |
科大联同北京天坛医院研究人员发现引致脑海绵状血管瘤的新元凶

香港科技大学(科大)及北京天坛医院的研究团队近日发现一个新的突变基因,可导致一种名为「脑海绵状血管瘤」(Cerebral Cavernous Malformation, CCM)的脑血管病变。目前全球约有一千至三千万的人士患有此症。

虽然科学家已知CCM1、CCM2及CCM3是引致CCM的三个突变基因,但三个基因主要影响有家族遗传性的CCM病患,而他们只占所有CCM个案的百分之二十。余下的百分之八十非家族遗传个案,至今成因仍然不明。

如今,由生命科学部兼化学及生物工程学系助理教授王吉光以及北京天坛医院曹勇教授带领的研究团队,分析了113名CCM患者的基因组数据后,发现于四种CCM患者当中,几乎所有于脑血管中长有爆谷形状肿瘤,亦即四种CCM患者中属最为普遍的二型1的患者,均出现一个名为「MAP3K3 c.1323C>G」基因突变。

现时,磁力共振成像(MRI)是一种医生常用于诊断CCM的「非入侵性」方法。然而,MRI只能让医生知道血管瘤的大小及类别;至于是哪一个基因突变导致CCM,医生一般则只能透过手术以及化验得知。不过,科大研究团队设计了一个计算机程序,可以评估MRI 影像所显示的血管瘤与MAP3K3 c.1323C>G基因突变关系的概然率。因此,病人毋须「开刀」便得知是否存在MAP3K3 c.1323C>G基因突变,不但能减低施手术可能带来的脑出血或脑神经功能缺损等风险,亦可令病者及早展开更针对性的治疗。

科大王教授表示﹕「研究除了为CCM的基因图谱开辟新方向,也为MAP3K3 c.1323C>G基因突变与CCM二型患者的关联性带来线索。团队设计的计算机程序,又称决策树模型(decision tree model),为实现CCM基因的非入侵性诊断迈进一步。我们希望有关发现可以有助找出治疗CCM的新靶标,促进药物发展,在不久的将来惠及病人。」

研究成果已在科学期刊《The American Journal of Human Genetics》发表。

1于四种CCM中,CCM二型最为普遍https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6924279/

研究与创新 |
HKUST Scientists Discover How Antibiotics Target Bacterial RNAP to Inhibit Its Gene Transcription

(This article was published on EurekAlert! on May 4, 2021)

 

A group of researchers at the Hong Kong University of Science and Technology (HKUST) has uncovered the mechanism of how DNA is being melted to start bacterial gene transcription and how one class of antibiotics inhibits this process – an important way in killing bacteria. This discovery provides useful insight on the development of new antibiotics for bacteria that is antimicrobial resistance.

The emergence and spread of new forms of resistance remains a concern that urgently demand new antibiotics. Transcription is a vital process in bacterial cell, where genetic information in DNA is transcribed to RNA for the translation of proteins that perform cellular function. Hence, transcription serves as a promising target to develop new antibiotics because inhibition the transcription process should effectively kill the bacteria. Bacterial RNA Polymerase, the core enzyme for transcription, must load the DNA and separate the double-stranded DNA to single stranded DNA to read the genetic information to initiate transcription. This process is also called DNA melting and is facilitated by the opening and closing of the loading gate of RNA Polymerase. The loading gate contains two flexible pincers (clamp and β-lobe) resembling the shape of a crab claw. DNA melting via this loading gate is a multi-step and highly dynamic process, and it provides a promising strategy for the design of novel antibiotics by inhibiting this process. Yet, the understanding of DNA melting requires a detailed understanding in the movements and dynamics of the loading gate, the lack thereof hampers future development of antibiotics.

To offer new direction for more effective therapeutics, a research team led by Prof. Xuhui HUANG, Department of Chemistry and Department of Chemical and Biological Engineering at HKUST, recently discovered the working mechanism of an antibiotics, Myxopyronin, by targeting the movement of the loading gate to inhibit the DNA melting prior to bacterial gene transcription. The research team identified a partially closed form of the flexible clamp domain, into which an antibiotic called Myxopyronin can bind with. The binding of Myxopyronin to the RNA Polymerase diminishes the gate's ability to close, eventually inhibiting the DNA melting, which is vital for the survival of the bacteria.

More interestingly, the research team also found the unprecedented role of the β-lobe during the loading of DNA to the inner cleft of RNA Polymerase. They discovered that the opening of β-lobe is sufficient to accommodate the loading of double helix DNA without opening the Clamp. The role of β-lobe has not been previously reported, and this finding opens the opportunity to the development of new antibiotics targeting the β-lobe of RNA Polymerase to halt transcription.

"The shape of bacterial RNA polymerase resembles a crab claw that works like a pincer. The shape and flexibility of the two pincers are important for RNA Polymerase to hold and separate the double-helix form of DNA into single-stranded. We showed that an antibiotic that targets the movement of the pincers would be a promising as a drug candidate" said Prof. Huang. "What is more exciting, is that we also discovered a novel critical role of the β-lobe that can serve as a new target for future antibiotics development."

This work is made possible only with the quasi-Markov State Model (qMSM) recently developed in Prof. Huang's lab. qMSM is built from extensive all-atom molecular dynamics simulations, and successfully predicts dynamics of RNA Polymerase's loading gate at atomic resolution and millisecond (10-3 second) timescale. This new method adopts the generalized master equation formalism to encode non-Markovian dynamics, which has advantages over the popular Markov State Models based on Master Equation. Hence, it is especially promising to be applied to study complex conformational changes of proteins.

The first author of this work: Dr. Ilona UNARTAR is a long-time HKUST affiliate who completed her undergraduate, PhD, and currently conducts her post-doctoral training all at HKUST from Department of Chemistry and Bioengineering graduate program. Other collaborators of this work come from Kyoto University and King Abdullah University of Science and Technology.

This study was recently published in the scientific journal Proceedings of the National Academy of Sciences.