生命中心李毓龙应邀《Neuron》杂志采访，畅谈光学成像工具发展及全脑研究
作为神经科学领域的顶级期刊之一，《Neuron》每年在美国神经科学学会年会同期出版主题综述合集。当下，疫情仍然在全球肆虐，结合特殊的时代背景，《Neuron》杂志组织了系列专刊，通过 “NeuroView”和“Q&A”（问与答）等形式，邀请了不同地区、背景与职业阶段的神经科学研究者就个人经历、对领域的认识与展望以及疫情下的科研和生活等内容进行了分享。
2021年11月3日出版的《Neuron》专刊中，北京大学、生命中心李毓龙以问答访谈的形式对有关光学成像工具发展及全脑研究相关的多个重要问题进行了个人分享。
李毓龙博士本科毕业于北京大学生命科学学院，于2006年获得美国杜克大学神经生物学博士（导师：George Augustine教授），之后在斯坦福大学进行博士后训练（合作导师：Richard Tsien教授），现为北京大学生命科学学院长聘教授，生命科学联合中心、北京大学-IDG/麦戈文脑科学研究所研究员，博士生导师。李毓龙博士为国家杰出青年基金、首届“峰基金”、首届“科学探索奖”及北脑学者获得者，还曾获“谈家桢生命科学奖”和“张香桐神经科学青年科学家奖”等。2012年，李毓龙博士在北大组建了自己的实验室，聚焦于神经元通讯的基本结构--突触，从两个层面上开展研究工作：一是开发新型成像探针，用于在时间和空间尺度上解析神经系统的复杂功能；二是借助此类工具探究突触传递的调节机制，特别是生理及病理条件下对神经递质释放的调控。课题组近期工作发表在Cell、Nature、Nature Biotechnology、Nature Neuroscience、Nature Methods、Neuron、eLife等高水平期刊，详见实验室主页：http://yulonglilab.org/。
Li Lab大家庭合影
在本期的访谈中，针对神经科学中最迫切需要解决的问题，最有可能出现新进展和突破的领域，实验室今后的研究方向，对人工智能在神经生物学研究中应用的看法，对未来神经生物学家的培养，疫情对个人生活、工作、学生培养、实验研究及文章发表的影响，对建立科研公平的看法及相关贡献，个人的科研偶像及科研灵感的来源等问题，李毓龙结合自身经历及感悟，从多个方面、多个维度做出了独到的分享。（想知道李老师的科研偶像是谁吗？答案就在后文）
下附中文译文及英文原文，以飨读者。
中文译稿（译者：王嘉琪）：
事迹介绍
李毓龙成长在中国福建省，在北京大学取得了生物物理和生理学专业学士，随后前往美国Duke University攻读博士学位，师从George Augustine教授，在博士期间专注于神经系统信号交流基本机制的研究。博士毕业后，他来到了位于美国西海岸的Stanford University，在Richard Tsien教授实验室开展博士后工作，并在此期间开发出了基因编码的红色pH荧光探针pHTomato。2012年，李毓龙回到了北京大学并建立了自己的实验室，他和他的团队专注于对用于研究神经系统信号交流机制的先进光学探针的开发。在北京大学的近十年间，李毓龙教授团队已经成功开发出了一系列的新型可遗传编码的荧光探针，它们被称为GRAB（GPCR activation-based）探针，这些探针能够在多种模式生物中很好地应用于生理条件下乙酰胆碱、多巴胺、去甲肾上腺素等神经信号分子的动态监测。除此之外，李毓龙实验室还开发出了首个完全遗传编码并能够功能性标记细胞间电突触连接的光遗传学工具——PARIS（pairing actuators and receivers to optically isolate gap junctions）。同时，他的团队还在GPCR功能的研究上有所突破，他们鉴定了胆汁酸受体MRGPRX4以及它在胆汁淤积导致的瘙痒中的作用。在科学研究之外，李毓龙也热心于教学工作，他不仅参与多门本科生以及研究生的课程教学，同时也承担着北京大学生命科学强化挑战班的教学指导工作。
1、在您看来，神经科学领域最迫切需要解决的问题是什么？
我认为现阶段最迫切需要解决的问题依然是研究清楚不同神经元以及神经环路的功能。正因为大脑十分复杂，我们至今对于不同神经元在不同行为中的作用，尤其是在人类行为中的作用仍然只有非常有限的了解。在神经系统中，哪怕只是在一个非常小的脑区中，也有着非常多种相互作用着的神经元；这里更复杂的地方在于，同一种神经元在不同的行为模式下也在发挥不同的功能。为了更好地了解这些复杂的功能和机制，神经科学家使用了很多动物模型来研究生理或者疾病下的大脑活动。例如在对神经退行性疾病的研究中，研究者们就利用一种神经毒素——MPTP处理的小鼠来模拟帕金森氏症的发病，进而使用这一动物模型研究帕金森氏症的发病机制与治疗方法。然而，在很多时候我们难以找到合适的动物模型，同时由于发病机制的不明确，许多神经疾病至今也没有很好的治疗方案。
2、您认为神经生物学的哪个领域最有可能出现进展和新的突破？
我认为，要想更好地了解神经系统，我们需要拥有精确调控包括神经元或胶质细胞在内的特定神经细胞活性的操纵工具，以及监测细胞间信号交流以及细胞内信号通路的检测技术。这一领域在过去几年中已经取得了长足的进步，例如光遗传学、化学遗传学的发展使我们能够调控特定细胞的活动，钙成像工具让我们能够实现细胞活性的可视化检测。因此接下来我认为十分重要的一步是开发出更多更强大的神经元活动检测工具，特别是对细胞间化学信号的监测工具。同时我们也需要注意的是，现在已有的大部分工具都只能在模式动物或培养细胞上进行，因而另一个巨大的突破可能会出现在对高精度、高准确性、非侵入，且可用于记录人类大脑活动以及化学信号动态变化工具的研究中。我认为这类工具的开发会极大地帮助我们实现从基础研究到人体层面的过渡，也有助于我们更好地理解人类如何思考、行动，并据此研究出更有效的疾病治疗方案。
3、您实验室目前已经开发出了许多非常好的GRAB探针，接下来您会在哪些新方向继续探索呢？您对哪些科学问题更感兴趣呢？
我们实验室以及世界上一些其他的实验室已经开发出了能够监测很多不同化学信号的探针，例如多巴胺、乙酰胆碱探针等。因此，我们接下来一方面要进一步地拓展我们的工具库，开发能够检测更多化学信号的探针，例如神经肽以及脂质等。同时，除了GPCR，我们也尝试基于其他蛋白骨架开发检测各种细胞内外化学信号的探针。例如D-丝氨酸，它是一种在睡眠和其他很多生理过程中发挥重要功能的化学信号分子；但是据我了解，它并没有明确的受体蛋白。我认为，或许通过合理的设计以及定向进化等手段，我们仍有机会能够开发出检测D-丝氨酸信号的荧光探针。
另一方面，我们也在尝试将探针的输出信号从荧光拓展到更多种不同维度的信号。比如说，相比光学方法，核磁共振在低侵入性的同时具有更好的组织穿透力，能够使研究者看得更深，获得全局的信号。但目前，我们却没有很好地造影剂来产生核磁信号。因此我们可以研发“多模式”的方法，例如通过融合光学与核磁或者PET的策略，开发能够以更好的时空分辨率观测大脑信号的工具。
最后，对在人体中检测大脑的调控机制而言，尽管拓展已有工具乃至开发新型工具是很具有挑战性的，我们仍然需要看到这类方法的重要性。在对人类大脑的研究中，简单的基因编码工具是不适用的，为了实现人体中的应用，我们仍需要开发更有力的技术。
除了对工具的开发，我们也致力于将这些新的工具应用到对神经系统的研究中，包括在生理及疾病环境下神经递质释放、回收的调控机制，以及他们所扮演的具体功能的研究。
4、目前人工智能在神经生物学研究中发挥了很重要的作用，您认为人工智能会带来怎样的革新呢？神经生物学家又该怎样更好地利用这样的技术呢？
我认为人工智能或者深度学习在神经生物学研究中是有很大用处的。比如，它能帮助研究者分析连接组学研究中大量的电镜成像数据，进而重构出大脑中复杂的连接，大大减轻研究者的负担。最近，Alpha-fold取得的进展也是一个很好的例子，它能够帮助我们预测蛋白质结构，尤其是在神经系统中有重要功能的蛋白。这能够帮助我们更好地了解蛋白间的相互作用、蛋白构象的动态变化以及蛋白与配体、RNA或DNA的相互作用等，从而让我们对神经科学乃至生物学的基本机制有更加深入的理解。同时，领域内现在已经有一些能够产出高通量数据的工具，例如高密度神经探针neuropixel，它能够实现大范围的神经细胞信号采集，而人工智能则能够在对这些大规模数据库的分析中发挥重要作用，帮助我们进一步破译大脑信号，使人们有机会更深入地理解神经元相互作用、相互交流的“语法”或“算法”，从而更进一步地认识这些信号如何指导更高级的行为。
5、您认为对于未来的神经生物学家的教育，当下最大的机遇以及挑战在哪里呢？
我认为其中最大的一个挑战和机会在于培养下一代具有交叉学科背景的领头人。神经科学需要多个学科的知识，如数学、物理、化学、生物学和心理学等。虽然我们人为地将神经生物学划分成了很多不同的分支，但是对于大脑功能的完整理解是需要进行知识整合的。因此，要想实现更大的突破，研究者常常需要利用来自多个学科的技术，比如当使用先进的光学方法来检测神经元活动时，必须要物理学家们设计出性能优良的显微镜，化学家们开发的最灵敏的探针，分子遗传学家们提供强大的遗传学手段，再加上心理学家们专业的理论以及技术。因此，下一代的神经科学领头人需要整合多个学科的知识以及技术以实现巨大的突破。正因如此，兼顾基础的神经生物学以及更多相关学科知识的教育就显得非常重要，这对于来自不同学科背景的教育者来说是非常有挑战性的工作。但这同时也是一个绝佳的机会，对于许多重要的问题，如情绪，成瘾以及神经疾病的机制等，学科间的联合都有助于对这些问题的研究乃至解决。
6、对于学生训练一个重要的部分是在会议上的口头汇报。您认为在疫情下学生们是否缺乏这样的训练机会呢？在您的实验室中，您是如何帮助学生们进行口头汇报的训练呢？
的确，我认为在疫情下学生们没有办法现场参与会议阻碍了他们对沟通技巧的锻炼，同时也缺少展示他们工作，并与全世界的同学同事们交流想法的机会。尽管现在有很多优秀的线上会议，但是我个人认为，比起线下会议，线上会议缺乏更多的感官输入，缺少了更大的感染力。同时我也注意到，因为在线上会议没法得到实时的反馈，人们很容易感到疲惫无聊，这使得这种思想的交流变得没那么有趣了。
在我自己的实验室里，多亏了北京市对疫情的有效控制，我们现在已经能够组织常规的组会，并且有机会参加一些国内的线下会议。与此同时，我们同样重视每一个能够邀请到国际学者的机会，并且鼓励学生抓住每一次机会进行海报展示以及口头报告。
7、您认为新冠疫情给您的生活带来了什么影响？
新冠疫情全球爆发时我们一家人正在美国洛杉矶进行学术访问，突然袭来的疫情让我们感到十分惊慌。在返回北京之前，我们花了很大力气才获得了口罩等医疗物资。直到现在，疫情仍然在影响着全世界的人们，在往常，我和妻子都会收到很多在国际会议汇报以及同行交流的邀请，然而在疫情影响下，这些线下的科学交流都很难实现了。在去年，我们的实验室由于疫情原因曾经被迫关停将近8个月时间。我们无法想象疫情竟给世界带来了这么多难以估量的变化。
8、您是如何平衡工作与生活的?
我和我的妻子宋艳都在各自的领域从事科研工作，我们8岁的儿子现在正在上小学。在平衡工作和生活这件事上，我们做的就是提前计划并协调好各自的时间，这样我们既能够管理我们各自的实验室，也有充足的时间与孩子一起度过美好的时光。当我们忙于工作，参加外地的会议时，我们会请父母帮忙照顾孩子。在新冠疫情流行的当下，事情会变得更具挑战性。不过幸运的是，北大为我们提供了非常多的帮助。我们可以通过举行在线会议与实验室成员和同事们沟通，同时也通过线上的交流建立和保持国际合作。
9、考虑到疫情期间许多实验室不得不关闭，您认为疫情对实验研究和发表过程有何影响?
除了与疫情相关的研究，我认为同行评审和发表过程没有太大变化。现在最突出的问题是许多科学家不能在实验室中进行实验研究。同时，在疫情时期，家庭等问题往往会成为研究者更沉重的责任，使他们困在其中，难以专注于科学研究。的确，一些实验室在疫情期间甚至被迫关闭了。但我不认为期刊为此降低了它们的标准。不过就我个人而言，我认为一些期刊要求的实验并不是完成科学工作所必需的。当在实验室工作对大多数科学家来说都很困难的时候，有时这些实验则会成为研究者们额外的负担。我认为这些事情可能是期刊需要考虑的。
10、我们该如何为来自少数群体的科学家们建立公平?在您看来，应该实施哪些具体的政策或行动?或者说在这方面，您所在的机构做了些什么?
科学领域的性别不平衡是众所周知的事实。在中国的生命科学领域，女性科学家仍然远远少于男性科学家。传统上，女性承担着更多的家庭和照顾孩子的责任，因此我认为需要特别关注女性科学家的职位晋升以及经费的申请。幸运的是，目前已经有了一些令人鼓舞的措施;例如一些资助机构现在正在考虑女性科学家的产假和年龄限制问题。然而，大部分女性科学家目前在科学社会中还没有得到很好的认可。我认为整个科学社会应该更加支持和包容女性科学家以及其他少数群体，给他（她）们更多的机会组织会议、申请和获得资金以及评议论文等。
11、您在科学上有榜样吗?如果有的话，是谁?为什么?
相比于一个特定的榜样，我更想提到的是许多科学英雄，包括Roger Tsien, Alan Hodgkin和Bernard Katz。不过在这份名单上排在首位的是钱永健教授(Roger Tsien)，我有幸在他的哥哥钱永佑教授(Richard Tsien)课题组接受过博士后培训，所以算下来Roger是我科学研究上的“师叔”。Roger的杰出之处在于他利用了跨学科的方法开发出基因编码的化学探针来可视化神经元信号等活细胞生物化学现象。这些光学工具可以无创地标记细胞，并高时空分辨率地记录细胞的活动。同时基因编码的特点使它们可以准确地标记特定的细胞，令我们能够理清复杂的神经系统。事实上，通过将我从天才的钱氏兄弟那里学到的精细的生理学方法与工具开发理论相结合，我的实验室正致力于开发先进的工具，以检测介导神经元相互交流或调节神经元活性的重要化学分子。
12、您是如何寻找您的科研灵感的?
我小时候喜欢读科幻小说，书里会描述未来世界的样子，以及人们探索宇宙的故事。我在上小学的时候沉迷于读《神秘岛》这本书。
长大后，我还喜欢读伟大科学家的自传，了解他们在科学领域的探险经历，知道了他们如何设计与进行巧妙的实验，并在其中收获意想不到但令人兴奋的发现。例如Roger在开发钙离子荧光探针时精妙绝伦的研究故事给予了我极大的启发。
英文原文：
Biography
Yulong Li grew up in Fujian, China. He studied biophysics and physiology as an undergraduate student at Peking University. During his PhD training, he focused on the fundamental mechanisms of neuronal communication under the guidance of George Augustine at Duke University. He then moved all the way to the west coast and conducted his postdoctoral research in Richard Tsien’s lab at Stanford University, where he developed a genetically encoded indicator called pHTomato. Yulong started his own lab at Peking University at the end of 2012. His research interests have been focused on developing advanced biophotonic sensors to understand the communication between neurons. His group has developed a series of novel genetically encoded fluorescent sensors, so-called GRAB (GPCR activation-based) sensors, for real-time detection of neurotransmitters and neuromodulators, such as ACh, DA, and NE, in vivo. His group also developed the first entirely genetically encoded optogenetic method PARIS (pairing actuators and receivers to optically isolate gap junctions) for functionally mapping gap junctions. Besides tool development, his group is also interested in illuminating the functions of GPCRs. His was one of the groups that independently deorphanized primate-specific Mas-related GPCR member X4 (MRGPRX4) with its native substrate bile acids and identified its physiological function in mediating cholestatic itch. Yulong teaches neurobiology to undergraduate and graduate students and guides the Undergraduate Research Honors Program in Biology (UHRB) program at Peking University.
In your view, what are the most pressing questions in neuroscience?
I would say the most pressing question is still what are the functions of different neurons and neural circuits. Because of the complexity of the brain, we still have relatively limited ideas of what kinds of neurons play what roles in the behaving animals, especially in humans. There are a great variety of different cell types intermingling with each other even in a very tiny brain region. To make things worse, the same types of neurons might have different functions depending on behavioral states. Given this complexity of the brain, we know very little about the physiological functions and regulatory mechanisms of these neurons. Neuroscientists have been trying to use model animals to investigate the basics of neuronal activity under both normal and disease conditions. For example, neurologists interested in neurodegenerative diseases, such as Parkinson’s disease (PD), have been using MPTP-induced PD model mice to study mechanisms of, as well as therapies for, PD. But most of the time, it is hard to find a suitable animal model, and it is still challenging to provide therapeutic means for neurological disorders or diseases.
Where do you see the strongest potential for progress and new breakthroughs in neuroscience?
I think to generally study or untangle the nervous system, we need to have precise ways to control or perturb distinct cells, including neurons and glia cells. And we also want to have ways to read out precise information of cell-cell communication or activities within the cells. We have had a lot of advances over the past few years. For example, optogenetics and chemogenetics have allowed us to control selective groups of cells, like different neurons. Now we also have ways to visualize neuronal activities, mainly from calcium imaging. So, I think the next steps will be to have more great tools to visualize the activity of neurons, especially the chemical communication and dynamics of neuromodulators. I also want to mention that the most current tools can only be applied to model organisms, but not humans. A big breakthrough, in my view, will be made in developing techniques to perform manipulation, visualization, and detection of neurochemical dynamics in the human brain with good precision, chemical selectivity, and non-invasiveness. I think that will help to bridge the gap between fundamental research and human biology, providing ways to understand how humans think and control, at the same time laying the foundation for therapeutic purposes.
With the robust GRAB sensor collection, what new directions are you going to explore next? Do you have any scientific questions that most interest you?
In terms of GRAB sensors to detect neuromodulators, we and others have demonstrated that a number of modulators’ sensors, such as dopamine and acetylcholine, can be very sensitive. So, one clear path we are going to take is to enlarge the repertoire of the probes—for using these probes to detect peptides and lipids. And we can even evolve novel designed scaffold to detect any kind of neurochemical or extracellular chemical of interest. For example, D-serine is a known important modulator for sleep and other physiological processes. To my knowledge, there is no such D-serine activator or GPCR. But through rational design and directed evolution, we might find a scaffold sensitive to D-serine and develop turn-on sensors based on such scaffold.
Another future direction for my group is to expand the fluorescence approach into other dimensions. For example, MRI or other approaches can look deep into the brain non-invasively and provide a holographic view or bird’s-eye view of the whole brain so that we can map these modulators. But critical contrast agents are still not available. So, by using multi-module modalities, for example, combining fluorescence, MRI, and PET, we could provide a better understanding of the brain in terms of both the spatial and temporal domains. And, finally, developing or expanding tools to study the human brain’s regulation would be challenging but is critical. The simple application of genetically encodable materials would not be suitable for human brain analysis. There should be new strategies designed to suit the purpose of human studies.
Besides tool making, we are equally interested in using our new tools to study the regulation of neuromodulators in release and recycle and in unveiling their precise roles and regulatory mechanisms in physiology and disease.
Artificial intelligence is playing a more important role in neuroscience research. What revolution do you expect it to bring to this field? How can neuroscientists take advantage of artificial intelligence?
I think there are a number of places that artificial intelligence or deep learning can help. For example, it can help to promote progress in connectomics by analyzing data from electron microscopy, which provides huge datasets to reconstruct every connection in the brain. In this way, artificial intelligence can help to save human labor. The recent breakthrough in Alpha-fold is also a good example. Alpha-fold helps to predict protein structure, including proteins functioning in nervous systems. It promotes further advancements, helping to understand protein-protein interaction, dynamics of protein-conformational changes, protein-ligand interaction, protein-RNA interaction, protein-DNA interaction, and so on. It would help to deepen our understanding of the fundamentals of biology and neurobiology. And we already have tools represented by the neuro-pixel electrodes that facilitate large-scale recording and provide large datasets. So, based on these large datasets with more precise information, artificial intelligence might provide ways for us to search the grammar, or the algorithm of neuronal interaction and communication, and how they guide behaviors.
What do you think are the biggest possibilities or challenges for the education of future neuroscientists?
I think one of the most major challenges and opportunities is to educate next-generation leaders with interdisciplinary backgrounds. Neuroscience requires a joint venture of using math, physics, chemistry, biology, and psychology. Although we have defined disciplines to separate neuroscience into different small branches, true understanding of the brain or neural systems requires integration. To make the biggest breakthrough, one often must rely on interdisciplinary approaches. For example, using cutting-edge optical methods to monitor neuronal activities requires the best microscope from physicists, the most sensitive probes from chemists, powerful genetic techniques from molecular geneticists, and unique approaches and thoughts from the psychologists. So, the next-generation leaders need to utilize multi-disciplinary approaches to make big new discoveries. It is important that education with some knowledge of fundamental neurobiology, as well as from other related fields, is provided, which is challenging for educators from different majors. But this is also a great opportunity, as many important questions requiring interdisciplinary approaches, such as mechanisms for emotion, addiction, and neurological diseases, are waiting to be solved.
Part of students’ training typically involves giving oral presentations at conferences. Do you think students have had less opportunity to develop their oral presentation skills because of the pandemic? How are you helping your lab members on this part of their training?
I do think that students not being able to attend conference in person is hindering their communication skills and lowering the opportunities to present their work and exchange ideas with their fellow students or colleagues throughout the world. It is true that there are good virtual conferences and presentations that people are attending. But, personally, I feel that during virtual meetings, the multisensory inputs are not exciting enough, or people are distracted, and I noticed people do get fatigued attending online conferences and giving presentations without real-time feedback or eye contact, which makes the intellectual exchanges less fun.
For my own group, thanks to the good control of the pandemic in Beijing, we now have relatively regular group meetings. We can also attend some domestic meetings. We take every single opportunity to host international visitors and encourage the students to give posters and oral presentations whenever it is possible.
In what other ways do you think COVID-19 has changed your life?
My family was in Los Angeles when COVID hit the world, and we were all horrified by the unprecedented pandemic. It took us great efforts to gather medical masks before we returned to Beijing. And even now, the pandemic is still not well controlled world-wide. My wife and I received many invitations to give talks at international conferences and intermingle with colleagues, and all these on-site scientific communications became impossible under the pandemic. Not to mention that our labs were essentially locked down for approximately 8 months last year. We would never imagine COVID-19 would lead to so many unpredictable changes to the whole world.
How do you manage work-life balance?
Both my wife, Yan Song, and I are scientists, and we have an 8-year-old son in elementary school. To manage work-life balance, what we do is to plan ahead and coordinate well so that we both get to manage our labs and spend quality time with our kid. On the occasions when we are both super busy with out-of-town meetings, we seek some help from our parents for babysitting. In terms of COVID-19, it, indeed, made things a lot more challenging. Fortunately, our university is very supportive. We can hold online meetings to communicate with lab members and colleagues and to establish and maintain international collaborations.
How do you think the pandemic has affected experimental research and the publication process, considering many labs have had to shut down?
Other than research related to the pandemic, I don’t think the peer review and publication process has changed much. Now the problem is that many scientists are not able to perform experiments in the lab. Instead, they are trapped or distracted by things like family issues, which is becoming a heavier responsibility under the pandemic. And indeed, some labs are even forced to be shut down. But I don’t think the journals have lowered their standard bar. Personally, I think that some experiments required by the journals are not all necessary to get the work completed. Sometimes they become an extra burden, especially at such time when lab work is hard for most scientists. So it might be something that the journals need to consider.
How can we build equity for scientists from underrepresented populations? In your view, what specific policies or steps should be implemented? Or what has been done in this regard at your institution?
It is a known fact that there is gender imbalance in science. For the field of life sciences in China, there are still far fewer female scientists than male scientists. Therefore, I think special attention needs to be paid in terms of job promotion and grant application for female scientists, who traditionally bear a much greater proportion of household and childcare responsibilities. Fortunately, there have already been some encouraging steps; for example, some funding agencies are now taking consideration of maternal leave and age-restriction problems for female scientists. However, a large proportion of female scientists are not yet well represented in scientific society. The whole scientific society should be more supportive and inclusive for female scientists and other underrepresented populations and give them more opportunities to organize conferences, apply for and obtain funding, review papers, etc.
Do you have a role model in science? If so, who and why?
Instead of one specific role model, I would say I have many scientific heroes, including Roger Tsien, Alan Hodgkin, and Bernard Katz. But on top of my list is Roger Tsien, who is also my “scientific uncle” as I was lucky to have my postdoctoral training with Roger’s elder brother, Richard Tsien. Roger is brilliant in the way he used interdisciplinary approaches to develop chemical-genetic-encoded probes to visualize live-cell biochemistry, including spying on neuronal signaling. Those optical tools can non-invasively label cells and read out their activities with high spatial and temporal resolution. And with genetic encoding, they can mark specialized cells with accuracy, allowing us to untangle the complexity of the nervous system. In fact, by combining delicate physiological approaches with the tool-developing philosophy I learned from the brilliant Tsien brothers, part of my lab’s ongoing efforts is focused on developing advanced tools for spying on important chemical molecules that mediate neural communication or modulate neural activities.
How do you find inspiration?
When I was young, I loved reading science fiction about how the world could become, how one could explore the universe. For example, I loved the book The Mysterious Island when I was in elementary school.
And later on, I liked reading great scientists’ autobiographies, learning about their adventures into science, how they design and perform smart experiments and got unexpected but exciting findings. For example, I was deeply inspired by Roger’s efforts in developing fluorescent probes for detecting calcium ions, which are beautiful both visually and conceptually.
(原文链接：https://doi.org/10.1016/j.neuron.2021.10.013)
