Chapter 175 Believe in the Wisdom of Our Ancestors
Unsurprisingly, the research on CRISPR-Cas6 has yielded nothing.
Looking at the results displayed on the instrument, Senior Brother Liu sighed: "Sure enough, it failed again."
"Isn't it normal to fail! The CRISPR system will generate so many kinds of We have only tried two proteins.”
“I think it’s not possible to do experiments one by one like a headless fly!”
"Senior Brother Liu, you have been doing experiments for so many years, are you still a headless fly? When other professors do experiments, don't they often try them one by one!" said a person next to him with a smile.
“Yes, how can we narrow down the scope if we don’t try them one by one.” Another person also said.
Senior Brother Liu turned to look at Liu Qian who was not far away, and then asked: "Liu Qian, when you were doing nucleoside modification before, you were like a headless fly. What did Zhang Wei think of? Just go where?"
Liu Qian thought for a while and replied: "It seems like this. At the beginning, we were all doing Toll-like receptors, and we did many cases, but they all failed. There was no result, and then Zhang Wei said to do nucleoside modification, and the result was achieved. "
"What was his basis for doing nucleoside modification?" Brother Liu then asked.
Liu Qian shook her head: "I don't know. At that time, he said, try to change your mind."
"You changed your mind and succeeded? Could it be pure luck? Could it be that this guy Is it all based on blind imagination when formulating experimental ideas?" Senior Brother Liu sighed helplessly.
At this time, Zhang Wei's voice rang out from the laboratory's loudspeaker.
“Let’s take a break. I bought coffee for everyone, from Starbucks! Come out and drink coffee!”
“Hey! Zhang Wei set up the experimental project like a headless fly. But his project team really provides enough snacks, including afternoon tea every three days!”
"Yes, Starbucks. I can't bear to buy it. Last time I went shopping with my girlfriend, the two of us bought one cup. We felt so bad."
"Isn't that right? One cup of Starbucks lasts for several days. There is no money for the meal. It is said that Teacher Zhang Wei is quite rich. He has treated us to meals and coffee these days. I heard that he paid for it out of his own pocket."
"He must be rich, don't forget. He scored 750 in the college entrance examination, and his scholarship alone is worth hundreds of thousands, which is enough to buy an apartment in the capital."
When they heard that there was Starbucks coffee, everyone immediately put down their work and walked over while chatting and gossiping. lounge.
"I bought a variety of flavors, including classic latte, American style, and new products. You can choose yourselves." Zhang Wei pointed to the Starbucks coffee bag in front of him.
Everyone was not polite and picked a cup of coffee one after another.
Zhang Wei took the remaining cup, took a sip, and frowned slightly. The taste was average, not as good as those domestic coffee chain brands of later generations.
“This quality control is bullying Chinese people who don’t understand coffee beans! In other words, Chinese people in this era still admire foreign fast food.”
Zhang Wei complained in his heart, and then asked Said: "CRISPR-Cas6 also failed, right? It doesn't matter, failure is the mother of success! Maybe we will succeed next."
Senior Brother Liu was the first to ask: "What should we do next? Yes Should we make other proteins of Cas6, go back to make Cas5, or continue to make Cas7?”
"What suggestions do you have?" Zhang Wei asked with a smile.
“As the saying goes, go ahead. We have done Cas3 and Cas6, so is it time to do Cas9?” one of them said jokingly.
“Good suggestion, let’s do Cas9 next!” Zhang Wei said immediately.
Zhang Wei had originally planned to do Cas9, but now someone happened to bring it up, so it would save him trouble, and he could just borrow the donkey.
"No, I was just joking! Don't take it seriously!" The man quickly explained.
"I think your suggestion is reasonable and well-founded!" Zhang Wei pretended to be dumbfounded.
"There is no basis for it! I just said a folk saying!" The man continued to explain.
“Folk sayings are based on the experience accumulated by our ancestors over thousands of years. Why is it 369 to go out, not 246 to go out, or 358 to go out? It must be these three numbers. It’s auspicious! Since it’s auspicious, the probability of success is higher,” Zhang Wei said with a smile.
"Teacher Zhang Wei, we are doing scientific research! What you said makes it seem like you have to look at the almanac to do experiments. How can it be like feudal superstition!" Someone else said.
“Einstein said that the end of science is metaphysics!” Zhang Wei explained.
"Einstein also said this? Why haven't I heard of it?" Senior Brother Liu muttered softly.
……
In the laboratory, everyone followed Zhang Wei’s arrangement and started the CRISPR-Cas9 experiment.
"This is too childish! Are you going out in three or sixty-nine? So you have to do Cas9?" Senior Brother Liu complained while staring at the experimental equipment.
“Yes, how can anyone do scientific research like this? I feel more and more that our project is unreliable.”
"It's not that the project is unreliable, it's that the people are unreliable! When other people do experiments, they have a plan, right? Why do they have to follow the experimental plan? It's good for him, as soon as he thinks of it, he will do it!"
"Even if there is no specific experimental plan, he still looks at the experimental results and then plans the follow-up experimental process based on the experimental results? As a result, he didn't even read the CRISPR-Cas6 experimental report we did earlier!"
"Haha, how can anyone rely on metaphysics? The key point is that he is so confident! He even pulled out the wisdom of his ancestors."
"I think it won't be long before our project is ruined. I listen. It is said that the funds we are using now are retained from the previous nucleoside modification project, and the funding application for the new project has not yet been approved! If this continues, the funding for subsequent projects will definitely not be available."
"Then. Don't we have to find a job as soon as possible? That's too bad. I can get a lot of experimental opportunities here, and the work is relatively easy. They are all simple experiments that do not improve oneself much," said a master's student.
"You'll get used to it. We've all been working as cows and horses." Senior Brother Liu said.
While everyone was complaining, Liu Qian stopped in front of the monitor. She stared at the monitor for more than a minute, and then she said: "Brother, come over and take a look. This There seems to be something wrong with the DNA fragments."
Immediately someone came over, looked at the numbers on it, and said, "Why are there more DNA fragments?"
"There are more? How come there are more DNA fragments?" Senior Brother Liu came over and looked at the experimental data carefully.
The next second, a ridiculous idea popped up in his mind.
"Could it be that these DNA fragments were cut?"
"Did CRISPR-Cas9 cut these DNA fragments? Did we really succeed?" Another exclaimed.
The three words "successful" instantly attracted everyone, and everyone came together. "Damn it, can it really be CRISPR-Cas9?"
"Three or sixty-nine people go out and they are really right? Isn't this too mysterious? Science Is the end of the world really metaphysics? ”
Everyone looked at each other and fell into silence.
A few minutes ago, everyone was complaining that Zhang Wei was unreliable! Some people have already begun to wonder where to find a new home after the project becomes obsolete.
However, with these words of complaint still echoing in my ears, the experiment was a success!
This reversal happened so fast that even the top academics at Tsingta University couldn’t catch it!
……
Everyone repeated the experiment and confirmed that CRISPR-Cas9 could indeed cut off DNA fragments, and then reported the results to Zhang Wei.
“It’s really CRISPR-Cas9! I’ve said it before, I believe in the wisdom of our ancestors!” Zhang Wei said with a smile.
Everyone looked at Zhang Wei speechlessly. Although the wisdom of the ancestors was completely nonsense, Zhang Wei really got it this time!
This is the first time I’ve seen someone do this kind of project. He just randomly set up the experimental content, and he actually achieved results so casually!
Is this good luck or a blessing from our ancestors?
Then before doing experiments in the future, should I buy a pig head to worship my ancestors? At least burn some incense and some yellow paper!
"Three, sixty-nine, go out, who suggested it? Credit him first!" Zhang Wei continued
"Can this be credited? It seems that what you need is not an experimenter , but a Taoist priest who can do calculations!" Senior Brother Liu complained in his heart
Zhang Wei continued: "I'll sort out the experimental report, and I'll ask the school for follow-up funds. Everyone has been working hard these days. We have a day off tomorrow. Let’s take a rest. Let’s continue working hard when we come back the day after tomorrow!”
“What should we do next after the holiday?” Senior Brother Liu asked.
Zhang Wei thought for a while and replied: "We have now determined that the protein that can cut off gene fragments is CRISPR-Cas9. Next, of course, we need to find a way to control this protein and perform the target gene sequence. Cutting.
There are two technical difficulties, one is how to control CRISPR-Cas9 to enter the target cell, and the other is how to identify the target cleavage site. I also have an idea, wait for me. Let’s sort it out and communicate with you!”
“Teacher Zhang Wei, do you really have an idea?” one of them asked in a low voice.
"What? You still doubt me as the project leader!" Zhang Wei asked with a smile.
“It’s not that I doubt it, I’m afraid that you will have to look through the almanac again when you go back. After all, we are doing scientific research, and we can’t rely on the almanac to do projects!”
...
Zhang Wei took the experimental report and found Meng Heming.
"The preliminary demonstration of the gene editing I did has been completed and the results have been achieved. Send me money quickly!" Zhang Wei directly threw the experimental report to Meng Heming.
"Are you getting results? So quickly?" Meng Heming took a few glances at the experimental report, his expression changed slightly, and he immediately asked: "Why isn't it a transcription activator?"
"When did I say we were going to make a transcription activator? I just said we were going to make a new gene editing technology." Zhang Wei replied.
"When Sinopharm and three academicians came, didn't you say we were going to develop nuclease technology for transcription activators?"
"That's what Academician Qian said. I just asked Academician Qian and he saw that I have read literature on this subject, but I didn’t say that I would do this kind of technology!” Zhang Wei put on an innocent expression.
"Hey! You don't make transcription activators, but you were still having a heated discussion with Academician Qian? You are just kidding us!" Meng Heming said angrily.
“Isn’t this just chatting? We have to find something to say when we have nothing to say! Academician Qian has already started talking about this, so I can’t continue the conversation, otherwise it will be disrespectful! Although I am young, This is a bit of a human touch!" Zhang Wei said cheerfully.
"Come on, I've become the unsophisticated one!" Meng Heming sighed, too lazy to talk to Zhang Wei anymore, but lowered his head and read Zhang Wei's experimental report.
"CRISPR? This is the short palindromic repeat sequence of the prokaryotic genome! Use the protein generated by CRISPR to cut the gene sequence to achieve the purpose of gene editing?"
After reading the basic description of the project, Meng Heming's face There was a moment of astonishment on the screen.
“How did you come up with this method? What’s going on in your head!”
“It’s all about when will you send me money!” Zhang Wei He crossed his legs and said with a pretentious look.
"This is the first time I have seen this kind of thinking. Please stop talking and let me think..." Meng Heming said, first taking off his glasses, rubbing his eye point, and then Start thinking seriously.
After a while, Meng Heming finally asked: "Theoretically, the protein produced by CRISPR can cut the DNA of the virus, which should be used for gene editing, but there is a problem.
CRISPR is bacterial Part of the immune system cuts the DNA of the virus in order to destroy the DNA of the virus and kill the virus so that it will not be affected by the virus.
What will happen if you use CRISPR for gene editing? How can we do follow-up experiments by destroying the target gene sequence and destroying the entire DNA of the target cells?” , immediately pointed out the biggest shortcoming of genetic scissors.
Genetic scissors are easy to use and the cost is not high, but the disadvantage is that the scissors are too sharp and it is easy to cut in the wrong position. As soon as the scissors are cut down, other gene segments may be accidentally damaged, which can easily cause genome instability.
Real-life animal experiments have found that when genetic scissors are used for treatment, a large number of unexpected single nucleotide mutations and deletions or insertions of larger gene fragments will be found. This is the reason.
If the previous gene editing technology was too inefficient, the hit rate was less than 25% when cut with one knife. Then the genetic scissors are too efficient. I originally wanted to cut it in half with one cut, but I never expected that the cutter would sputter and cut into eighteen pieces.
As for the question raised by Meng Heming, Zhang Wei had already thought of the answer. He said: "I have also considered it. The problem you mentioned will indeed arise. I can't think of a good solution for the time being. , currently we can only rely on the self-repair of cells.
When a DNA double-strand break occurs, the cell will try to repair it. If it is repaired by non-homologous end joining, it will be faster, but it may cause genetic damage. Changes in function.
Although it is possible to change gene function in a good direction, most of them are in a bad direction. Once non-homologous end repair connection occurs, it means gene editing fails. < br>
But if homologous recombination occurs, the situation is different. Although the repair speed of homologous recombination is relatively slow, it can accurately repair the cell's mechanism and repair the broken DNA, and the gene editing will be successful.
If homologous recombination can be used to insert into specific parts of the target gene, the problem you just mentioned can be solved. But this is not within the scope of my research this time. What I want to do this time is gene editing technology. "
Meng Heming frowned and thought for a while, then nodded silently: "The method you mentioned is feasible. If your gene editing technology is successful, there should be many scholars willing to work on it. On this basis, the technology of inserting homologous recombination is studied. "
Meng Heming continued to read the follow-up experimental report, his expression was surprised again.
"CRISPR-Cas9? Have you found a protein that cuts a genetic sequence? It’s only been a few days? There are hundreds or thousands of proteins, right? How did you find it? ”
"The main reason is that I believe in the wisdom of my ancestors!" Zhang Wei replied with a smile.
(End of this chapter)