Initial Foray into Scientific Research
In fact, before I became familiar with structural biology, which was in the autumn and winter of my sophomore year (Fall and Winter of 2021), I joined Jie Dong’s lab for a period of scientific research. At that time, I had absolutely no concept of scientific research; I found Jie Dong because I wanted to participate in the National Undergraduate Life Science Competition, and I was particularly interested in gene editing and protein-protein interaction networks. The project I participated in at the time was about protein purification and antibody preparation, so during that period, I learned a lot of wet lab techniques, such as operating bacterial shakers, extracting proteins, running nucleic acid electrophoresis/protein electrophoresis, and performing Western Blots, etc. I would like to express my special thanks to Jie Dong for giving me the opportunity to get started in scientific research.
Exposure to Cryo-Electron Microscopy
Also in the autumn and winter of 2021, I became particularly interested in astrophotography. By chance, I came across an introductory video on cryo-electron microscopy by Grant Jensen on Bilibili; I was attracted to it and clicked in to watch. Afterwards, it got out of control: I gradually began to realize that cryo-electron microscopy research was very in line with the biological research I aspired to, and it also had a peculiar fit with my hobbies at the time. So after learning more about cryo-electron microscopy research, around May of my sophomore spring and summer (i.e., around May 2022), I tried to contact Professor Xing Zhang, the director of the Cryo-Electron Microscopy Center at Zhejiang University. Here, I would also like to express my special thanks to Professor Zhang for giving me such a great opportunity. During the interview, Professor Zhang invited Yunjie Chang to join us, and asked me if I was interested in cryo-ET. At that time, I actually hadn’t heard much about cryo-ET, only about SPA, but I heard that cryo-ET had higher computational requirements, and could solve structures in situ, which I found amazing at the time, so I wanted to give it a try. So I officially joined Professor Xing Zhang’s lab, and under the guidance of Yunjie Chang, I learned and practiced cryo-electron microscopy related scientific research.
In the following time, I became familiar with the use of various data processing software for cryo-electron microscopy, such as IMOD, EMAN2, and Relion. Then I also learned about the data collection process, and helped write some Python scripts, such as scripts to improve the data collection efficiency of PACE-tomo. I suddenly discovered that I was actually quite suited for computational work, and I could also be very focused on such projects, often immersing myself in coding for an entire afternoon without moving. And at that time, I also received encouragement from Yunjie Chang and Professor Zhang, feeling that I was kind of quite talented in this area, so I was also greatly encouraged, forming a “positive feedback” in my understanding of cryo-electron microscopy. Of course, in this process, there were also many difficulties to overcome; I needed to self-learn Linux, self-learn MATLAB, equivalent to making up for a lot of basic knowledge in computer science, but looking back now, it all seems not a big problem.
Decision to Study Abroad and Participation in Overseas Projects
An interesting thing is that both Jie Dong and Yunjie Chang returned from Yale University. Although it sounds very silly now, I was actually quite fascinated by Yale University when I was in high school. Plus, Chang recommended that I study abroad, and all these factors combined, I decided to go abroad for my PhD to extend my worldview. So in the autumn and winter of my junior year (around November 2022), I signed up to participate in the Imperial College London Data Science Winter School. Although it was turned online due to the pandemic, I still hoped to experience the feeling of studying abroad in advance, and by the way, to see if I was suitable for studying abroad. Another reason for signing up for this program was that, whether for my hobbies(astrophotography) or for scientific research(cryo-EM), a profound understanding of images and image processing was very necessary, and seeing that this program had a computer vision related project (i.e., brain tumor segmentation based on neural network), I tried to sign up. During the course, I learned more about neural networks and image segmentation; during the project, I was mainly responsible for the coding. It turned out that I might have some talent in this area, at least our results won the Best Computer Vision Project award. Through this exchange and study, I indeed gained a deeper understanding of image processing and CNN.
In the spring and summer of my junior year (around April this year), I also participated in the international exchange course in the Department of Computer Science, which was also about machine learning and artificial intelligence. The lecturer was a professor from Brown University, and I scored 94 points, which was a pretty good grade. Then actually, I also learned Stanford CS231n and UMich EECS 498-007/598-005 on YouTube, taught by Justin Johnson, which were very detailed.
Of course, during this period, I also continued to develop methods related to cryo-ET resolution of membrane proteins under the guidance of Chang, such as methods for picking particles, and so on.
Going to Kai lab in Yale for Summer Intern
I contacted Kai Zhang at Yale in March, and I was very happy that he quickly agreed, and here I also want to express my special thanks to Kai for his help. In the Kai Lab, I mainly worked on the development of new methods for getting high-resolution structure of membrane protein in situ, and most of my time was still spent on computation and coding. I practiced a lot of numerical and analytical methods for image processing. (btw, later when paper is published, I can talk about the details inside, so stay tuned.)
What’s more, I participated in many lectures and conferences, which helped me learn much more about cryo-EM and beyond. For example, I listened in on MB&B 420a/720a(Macromolecular Structure and Biophysical Analysis) given by Joe Howard; and listened the lecture The impact of cryoEM in structural biology given by Richard Henderson, who was awarded the 2017 Nobel Prize in Chemistry, and Innovation by Evolution: Bringing New Chemistry to Life by Frances Arnold, who won the 2018 Nobel Prize in Chemistry. I even attended the Dean’s Invited Speaker Series held by Yale Engineering, where I listened C.C.Wei, the CEO of Taiwan Semiconductor, talking about his Ph.D. life in Yale. In a nut shell, the experience in Yale is pretty unforgettable.