Since the 21st century, the advent of the Super-Resolution Microscopy has become more and more essential in life science and biology research at subcellular and even single-molecule levels. This facilitated the scientists from different disciplines revealing a much more precise cellular image that had been otherwise masked due to the diffraction limit, leading to a new level appreciating molecular activities inside cells. Dr. Yandong Yin and his team will be utilizing "IT+IT" (the Imaging Technique + Information Technique) to understand the underlining physics of molecular activities and uncover the cell world with more and more super-resolved details.


Yandong YIN

Institute of Chemical Biology, Shenzhen Bay Laboratory   

Junior Principal Investigator

Research areas

Dr. Yin's research team is mainly engaged in developing super-resolution imaging technology, image mining technology, and in-situ single molecule tracking technology. By integrating Statistics, physics, physical chemistry, and chemical biology tools, the research team focuses on exploring the physical essence of the in-situ molecular dynamics of biomacromolecules at single-molecule level.


01 Nano-scale visualization of single molecules

In the science fiction "Three-Body Problem”, the author Liu Cixin, from his limitless imagination, painted us a glorious but dark picture of the universe, which not only does fill the fantastic starry sky with enormous details but also hides a lot more far behind. However, such unscalable macro world seems to be connected to the micro world, which is also unscalable just from an opposite axis. Starting from the human eyes, as we push the microscopes closer and closer to the skin, the blood vessels, and even deep into the nucleus, a comprehensive and exquisite picture of the nature of the human life is gradually unfolded to us—just like the sky being unfolded by the telescopes. We are thus just wondering if the micro world is just another macro  at a much smaller scale. With the advent of the Super-Resolution Microscopy technology at the beginning of this century, scientists have been gradually "seeing" the precise structures hidden in cells and have been stepping further and further in observing and understanding the nature of the life inside cells.

There are in general three types of Super-Resolution Microscopy technology: the Structural Illumination Microscopy (SIM), the spot-scanning-based  STED or MINFLUX, and the Single-Molecule Localization (SMLM) based technique which is what our lab is current working with. The underlying principle of SMLM is to resolve the spatially unresolvable information in a temporal manner. When many fluorophores are densely stacked and emit photons (being illuminated with continuous-wave lasers) at the same time, we will only be able to see  the highly overlapping Point-Spread-Functions (PSF) due to the diffraction limit, and thus cannot distinguish the accurate position of each of the fluorophores; whereas if we can somehow make each molecule emit photons “one-by-one”, we will be able to measure the exact position of each molecule individually, and finally reconstruct their spatial distribution with extremely high resolution.

After visualizing clearly, it is necessary to "understand" clearly as well. Therefore, in addition to the Super-Resolution Microscopy technique, the second direction in our lab is to develop technologies that analyze and quantify the distribution characteristics of these densely stacked molecules through statistics and/or AI-based methods. Do they stack together in such a stochastic way, or do they follow a certain rule to form a certain shape or pattern although seemingly chaotic? while the first technology, Imaging technique (IT), is to see the image "qualitatively clearer", the second technology, Information technique (IT), is to understand the image "quantitatively clearer".


02 Learning “new” knowledge across multi-disciplines

During high school, I was a little better at math and physics but seriously weak on literal subjects like politics and history, but because Gaokao doesn’t require literal subjects for students in science and technology majors, , I got through it anyway. After being admitted to the college of chemistry at Peking University, ironically, I found myself still a little better at math and physics but weak at my major chemistry. After I joined in Professor Zhao Xin-Sheng's research team, who was working on the cutting-edge single-molecule techniques and recruiting students from multi-disciplines for integrated research, I fortunately found that being a chemistry major, my math and physics are not useless.

It was in Prof. Zhao's lab that I started to get to study the conceptual basis of single molecule analysis. At that time, it was a completely new and challenging field for me: on the one hand, measurements at the single-molecule level enabled me, for the first time, to actually “visualize” the stochastic properties of the molecular dynamics, and to actually make use of the statistical techniques such as Maximum Likelihood, Bayesian Inference for single-molecule observations; On the other hand, observing single molecules requires the microscope instruments to be of higher sensitivity and spatiotemporal resolution, which also triggers my interests in instrumentation of advanced microscopy platforms with state-of-the-art technologies.

Prof. Zhao is rigorous on both science and training young scientists/students. . During my graduate study, Prof. Zhao payed a lot of time and efforts instructing every of us in designing experiments, building microscopes, sample preparation, and analyzing data, etc., full of passion and patience. For our own experimental data, he often knew better than we did -- he could always see through the data and led us to an “Eureka” that hidden behind the seemingly irrelevant data plots. Prof. Zhao’s enthusiasm and rigorousness towards science deeply influenced me, and I am always grateful for the experience during my graduate training in his lab. This probably is the most important reason for me to choose academia as my career path.

Working in the interdisciplinary area, what is most challenging for me is probably the lack of knowledge in some unfamiliar fields. My solution to these issues was to simply take courses (self-teaching or on-line) from the “first-grade” so that I could learn not only the knowledge but also the intrinsic and systematic logics underling the entire field. It was probably boring taking courses as a real “first-grade”, but it was really fun and efficient for me going back with real scientific questions. Honestly although to study from the “first-grade”  had stolen time and efforts from the bench work, I found that in the long run, the systematic logics from various disciplines did bring me different perspectives and had widened my vision on my research.

03 Building a new research platform in Shenzhen Bay

It has been nearly one year since I joined the Shenzhen Bay Laboratory, and I am glad that I was one of the team. First, the deployment of the laboratory is multi-dimensional, ranging from the fundamental research to translational research and then to the mission-driven projects addressing major diseases. Not only has this gathered researchers from different disciplines to work together as an highly integrated team, but also provided sufficient opportunities for us to learn from each other, and thus to broaden our vision in science; Second, the laboratory's foresight in in the great importance of the fundamental research. The Shenzhen Bay Laboratory  provides us greater support as well as a freer research atmosphere, and ensures us being able to survive the competence while digging into those “high-risk” scientific topics; Third, the administration team’s high proficiency guaranteed our efficiency in research and prevented us from being exposed to some daily trivia.

One important interest of our team is to quantitatively analyze the physical mechanisms of the molecular dynamics and that of the molecule-molecule interactions inside cells, especially when the target molecules are buried in the dense and seemingly chaotic cellular environment, such as in-situ chromatin dynamics, DNA replication and transcription, and many other important biology processing in the nucleus (which is dense and crowding). So far, we have built a Single-Molecule Localization microscopy platform and a TIRF microscopy system for in vitro single molecule dynamic analysis, and are finalizing the software part for the platforms. We hope that these systems will be put in use quickly. In the near future, we will be setting up the third microscopy platform, on which we will be focusing on developing a new super spatiotemporal resolution microscopy for quantitative imaging.

I am now also trying to establish a small but comprehensive team which I hope  to be enthusiastic and open-minded in research. For scientific research, I think the second most important quality  is the curiosity, while the first important one is to be able to be patient in your curiosity. Hope that in this team, people from different fields can learn from each other and grow together.



Brief introduction to the Principal Investigator

Dr. Yin received his bachelor's degree and doctor's degree from College of Chemistry and Molecular Engineering (CCME) of Peking University in 2008 and 2013 respectively, and later, he worked as a postdoctoral fellow and researcher scientist at NYU Grossman School of Medicine. He is now a Principal Investigator at the Institute of Chemical Biology, Shenzhen Bay Laboratory and an Assistant Professor at The School of Chemical Biology and Biotechnology (SCBB) of Peking University. Dr. Yin’s Group is focusing on innovating biophysical technologies in Super-Resolution Imaging, Image Deep Mining, and live-cell Single-Molecule Tracking. The major interest is to understand the biological physics at single-molecule level by integrating the state-of-the-art techniques in optical imaging, data mining, and chemical biology. Up to now, he has published a number of papers as the first author and correspondent in journals such as Molecular Cell, Nature Communications, PNAS, etc.


Honors

• 2013  Outstanding Doctoral Dissertation of Peking University, Peking University

• 2012  National Scholarship for Outstanding Graduate Student of China

• 2012  Celanese Scholarship, Peking University