Abstract
摘要:腦是人體中最複雜的一個器官,擔負重要的心智與認知功能。腦由異質的組織與多元龐雜的神經細胞所組成,瞭解腦的發育與腦部疾患是當代神經科學最具挑戰的課題。考量人腦的複雜性及活體研究的限制,近期研發的腦部類器官(一種體外神經細胞模型)提供了一個可行且極具潛力的簡化研究平台。目前,台灣在研發腦部類器官上,遠遠落後世界各國。經由與美國哥倫比亞大學的梁錦榮院士、Xu Bin教授及他們領先全球的研究團隊合作,以腦部類器官探討神經細胞如何逐步發育成具有特定功能的神經核與具有神經可塑性,從基礎著手藉以逐步瞭解建構複雜認知功能的核心基礎。本計畫的工作目標包含:(1) 以工程與生物學方式建構與優化誘導型多功能幹細胞發育成三維腦部類器官的過程,重現人類腦部發育的過程。(2) 整合生物感測及驅動元件技術與微流道晶片技術,進一步探討腦部類器官於神經型態與神經迴路發展與電生理特性上的關聯性。(3) 使用神經電生理與生物感測技術,在不同發育階段之腦部類器官中探討最基礎的神經可塑性與探索基礎學習的神經機制。(4) 建立病患(如小胖威利症)腦部類器官平台用以研究神經發育疾患。透過龍門計畫,團隊成員可以學到最新進展與促進雙邊合作,並讓這些先進技術在台灣發揚光大。
Abstract: Human brain is one of the largest and most complex organs. It has remarkable cognitive capacity that controls higher-level functions such as thought, behavior, emotions, learning, and memory. The brain is an extremely complex system of heterogeneous tissues and consists of an extremely diverse array of neurons. Understanding human brain development and brain disorders is one of most fascinating challenges in neuroscience. To understand and study the basics foundation of the brain and mind, the recent development of brain organoid opens a promising avenue to overcome many obstacles. Unfortunately, currently, Taiwan is lagging far behind the leading teams on the development of brain organoids to study the basics of brain development and neural functions under normal and pathophysiological condition. Profs. Kam Leong (梁錦榮院士), Bin Xu, and their world`s leading research teams at Columbia University Medical Center are co-developing a novel platform for generating high quality brain organoids and applying the brain organoid model to address the critical questions in human brain development and basic neurocognitive functions. Brain organoids, also known as neural or cerebral organoids, are human pluripotent stem cells (PSC)-derived three-dimensional (3D) in vitro culture systems that recapitulate the developmental processes and organization of the developing human brain. The purpose of this collaborative project is to form the joint force to further improve the quality of 3D brain organoids to the degree comparable to that in the developing human brain and investigate the foundation of basic neurocognitive function in the developing brain. Through this partnership, our team members can learn the recent advances in the development of brain organoids at Columbia University and also establish all related cutting-edge techniques in Taiwan. There are 4 specific aims in this 2-year joint project. (1) Taking advantage of the advances of the biomedical engineering and neurobiology platform developed in Profs. Kam Leong and Bin Xu’s labs, we would like to take part in the optimization procedure of 3D brain organoid model to recapitulate critical features of human brain development. (2) In addition, we will integrate our technical advantages in engineering manufacture and biosensor development to broaden the feature extraction from the brain organoid model, including neuromorphology, the formation of neural circuitry, gene expressions, and electrophysiological properties. (3) To explore and investigate the simplest forms of neuroplasticity and basic learning in the developing 3D brain organoids using electrophysiological recording and biosensor. (4) Furthermore, we will prepare a brain organoid prototype to investigate the cellular and molecular mechanisms of neurodevelopmental disorders using the Prader-Willi syndrome (PWS, 小胖威利症) model. The Dragon-Gate Program will play an essential and vital role for us to build up an international collaboration and research team to fill the gap in this novel interdisciplinary filed.
Keyword(s)
哥倫比亞大學
腦部類器官
腦晶片
誘導型多功能幹細胞
神經發育
神經型態
電生理特徵
生物感測
神經認知功能
神經可塑性
基礎學習
小胖威利症
Columbia University
brain organoid
brain on a chip
pluripotent stem cell
neurodevelopment
neuromorphology
electrophysiological property
biosensor
neurocognitive function
neuroplasticity
basic learning
Prader-Willi syndrome