Chapter 174 This project is unreliable!
Three doctoral students, plus four graduate students, this kind of team configuration is a high-quality team even for Tsinghua University, the highest university in China.

The appeal of "Science" was still huge. In terms of China's scientific research level at that time, being able to sign a paper published in "Science" was considered a very impressive scientific research achievement. It was more than enough to be used as an associate professor in ordinary universities. .

The seven people under Zhang Wei all came here for this signature.

In the laboratory, seven people were divided into two groups, three doctoral students gathered together, and the other four master's students gathered together.

"Do you think Zhang Wei's project can be successful this time? Brother Liu, I heard that you are very familiar with Zhang Wei. Please tell us a little bit." One of the doctors asked.

"If you thought Zhang Wei's project was unreliable, you probably wouldn't have come!" Senior Brother Liu asked.

"Didn't Zhang Wei succeed in a nucleoside modification project before? And I heard that when Sinopharm came to inspect, he dared to issue a military order in front of three academicians. Maybe it can really be successful, so he came here." Speak up.

Another person said: "It would be best if it can be like the nucleoside modification project. After it is completed, there will be some funds left. If I can get tens of thousands of dollars from Zhang Wei, I can also turn my own project into a project." Once done, the graduation thesis will be completed.”

"You are quite good at calculating. This project hasn't started yet, and the balance of the funds has been included?" Senior Brother Liu said.

"We all know that Zhang Wei had a lot of money left over from his last project, and he probably didn't even use half of the funds. After this project is started, he must still apply for funds from the school, right?

The more you contribute to the project, the more you will get when you are rewarded based on your merits in the future. Let me give you a guarantee first. If anyone’s contribution to the project is really big enough, it is not impossible for us to jointly sign as the first author! "

When working under other professors, no matter how big your contribution is, you can only get a second author. Zhang Wei's willingness to give co-signed first authors here has obviously exceeded the treatment that other professors can give.

If you want to make a horse run fast, hanging a carrot in front of the horse is a good way.

The three doctoral students had different ideas, and the other three master's students asked Liu Qian whether Zhang Wei was easy to get along with.

Next are gel electrophoresis equipment, which can analyze the size and number of gene fragments; nucleic acid analyzers and fluorescence detectors, which can measure the concentration, purity, hybridization and fluorescence signals of gene samples.

Everyone's expressions fell into Zhang Wei's eyes, which made him feel very satisfied. This pie painting was very effective.

"Everyone is here. All the senior brothers and sisters have been in the Biology Department longer than me. They must all know each other. Personal introductions are omitted!
Let’s take inventory of the experimental equipment first. If anyone has equipment that they are good at, you can put it forward now, and it will be prioritized when arranging experiments in the future. "

Zhang Wei came to the ultra-clean workbench as he spoke and began to check the centrifuge, PCR instrument, electrophoresis instrument and other equipment.

This is equivalent to using one and a half project funds to do a project. I think there will always be some savings! When the time comes, just based on this relationship, no funds will be allocated to me. "The man continued.

Moreover, Zhang Wei's actual experimental level, even if he is a second-rate operator, is really far behind compared with the graduate students of Tsinghua University. If he were allowed to do it by himself, it would only take him a long time to do it, but it would reveal that he is a second-rate experimenter. It will not be conducive to establishing prestige when the time comes.

Footsteps sounded from outside, and Zhang Wei finally arrived at the laboratory.

As for what kind of signature you can get, it all depends on your contribution to the project! In my team, we don’t look at seniority or relationships, only the contribution to the project.

Few of the top academic experts would conduct experiments themselves. They usually arrange for others to complete experimental tasks. From now on, Zhang Wei will also move towards directing others.

Everyone looked surprised when they heard that they could be jointly signed as the first author.

Zhang Wei, who has been in the system for most of his life, is naturally familiar with PUA behavior in the workplace such as pie-making.

I will also make it clear in advance here that as long as you are not lazy and can complete the experimental tasks on time, your signature will definitely be given to you when the paper is published.

Centrifuges and various containers are mainly used to extract, purify and quantify samples, while PCR machines and QPCR machines are essential equipment for gene-related experiments.

Zhang Wei said: "From now on, our project is officially established. I know that everyone who came to my project must have come to sign the paper.

While inspecting the equipment, Zhang Wei was also constantly asking and recording. He wanted to know what equipment and types of experiments these seven experimenters under his command were good at, so that he could arrange their work later.

In addition, there are such things as constant temperature mixers, vortex oscillators, dilution equipment, etc. Including temperature control, plot workbench, disinfection equipment, and even waste treatment also require a dedicated system to maintain.

After checking the equipment, Zhang Wei had a preliminary understanding of the abilities of his team members.

Zhang Wei is not worried that someone will really contribute enough to the project to be ranked as the first author.

Genetic scissors are a Nobel Prize-level achievement. If you want to realize this technology, what experiments should be done and how to do the experiments are all the results of research by Nobel Prize-winning experts.

If these seven graduate students really had that academic level, they wouldn't have gone to Zhang Wei to work as lab technicians, and they would have been able to host big projects themselves.

Next, Zhang Wei took out seven confidentiality agreements from the bag and handed them to everyone.

"This is the confidentiality agreement for our project. I hope you will read it carefully and sign it."

"I still need to sign a confidentiality agreement!" someone said.

"I am also a gentleman before a villain. After all, this is the first time for everyone to work on a project together, and we are not very familiar with each other. Signing a confidentiality agreement can also increase mutual trust!" Zhang Wei said with a smile.

After everyone signed the confidentiality agreement, Zhang Wei took out the project book.

"I think you should have heard something before coming here. Our project this time is to develop a new editing technology."

"Yes, I have checked a lot of foreign literature in the past two days, and I have a certain understanding of transcription activator-like effectors. And I also checked the latest foreign research in this area, and found that even Americans have just conducted Research in this area." Senior Brother Liu said immediately.

Another doctoral student said: "Transcription activator-like effector is a protein secreted by Look for V-shaped yellow-brown lesions on the leaves, which is most likely to be infected with Xanthomonas. "

“If you want to isolate Xanthomonas from vegetables, you can use a culture medium like CS20ABN. However, since Xanthomonas is highly dependent on pH, you can maintain the pH value at 6.5 by adding additional potassium dihydrogen phosphate. It can significantly improve the recovery rate of Xanthomonas!" the third doctoral student said.

These three doctors had obviously done their homework before coming here.

The news previously released by Zhang Wei was to develop transcription activator-like effector nuclease technology, so the work done by the three doctoral students was also in this area.

It seems that these three people are worthy of being PhDs from Tsinghua University. Before joining the project team, they not only clarified the principles of the entire project, but even planned the experimental steps. They also inquired about the experimental progress of their foreign colleagues. . It is probably equivalent to having already understood everything the teacher is going to say in this class before going to class. Even many questions have been solved by looking up the information on your own. This is the learning rhythm of a typical top student.

But they didn't expect that what Zhang Wei really wanted to do was not the second-generation transcription activator-like effector nuclease technology, but the third-generation genetic scissors.

But Zhang Wei still showed a satisfied smile, which was regarded as affirmation of the work attitude of the three doctors.

Zhang Wei then distributed the project plan to everyone.

"Not a transcription activator? CRISPR?"

"I remember this seems to be a genetic sequence of bacteria, right?"

"The full English name is Clustered Regularly Interspaced Short Palindromic Repeats, clustered regularly interspaced short palindromic repeat sequences."

Everyone looked at Zhang Wei in surprise.

Everyone thought that they were going to use transcription activators for gene editing technology, but they didn’t expect that CRISPR would suddenly appear!

Zhang Wei said: "First of all, is there anyone who doesn't know about CRISPR?"

No one shook their heads. The quality of graduate students at Tsinghua University was still very good. Everyone knew what CRISPR was.

"Then you all know the role of CRISPR, right?" Zhang Wei then asked.

"CRISPR is part of the bacterial immune system. The protein transcribed from this gene sequence can destroy the virus's genes. Therefore, CRISPR is also a unique immune system of bacteria." Brother Liu took the initiative to answer.

"Then what is the principle of this protein destroying viral genes?" Zhang Wei then asked.

"This protein can cut a piece of RNA that serves as a guidance tool into the viral DNA, and then blocks it at this entry point, which can split the viral DNA into two pieces. When multiple segments cut into the viral DNA at the same time , the DNA of the virus will be cut into many segments.”

As Senior Brother Liu answered, his speaking speed became slower and slower, as if he had realized something.

Zhang Wei said: "Brother Liu is right, since CRISPR's immune system can cut off the DNA of the virus, it can also cut off other gene fragments.

If we can master this mechanism, does it mean that we can use this mechanism to perform gene editing? This is the gene editing technology I want to do! "

Zhang Wei's words shocked several people instantly. While the four master's students were still thinking about the feasibility, the three doctoral students were already full of surprise.

"Teacher Zhang Wei, your idea is a bit too... too... too shocking!" one of them said.

"You originally wanted to say it was too whimsical?" Zhang Wei asked with a smile.

"To be honest, it's a bit whimsical. Using the immune system of bacteria to make genetic scissors, can this be done?"

"I have told you the theoretical direction, do you think it is feasible?" Zhang Wei then asked.

Several people frowned and thought for a while, but in the end it was Senior Brother Liu who nodded: "Theoretically, it is indeed feasible, but it is still difficult for me to imagine using CRISPR for gene editing."

Zhang Wei said: "In the 1960s, scientists used the homologous recombination characteristics in the DNA replication process to develop a 'gene targeting' technology to achieve precise modification of a single gene. I think you all Have you heard of this technology?

The project we are currently working on actually has many similarities with this 'gene targeting' technology, which I named 'gene scissors'. Once this technology is successful, the entire field of life sciences will be subverted. Scientists can edit the genome of living cells. Countless new possibilities will be born in the entire field of biological sciences! "

Zhang Wei gave another shot of chicken blood, which made the four master's students excited and eager to get involved in the experiment right away.

However, these three doctoral students are not so easy to fool, especially Senior Brother Liu, who will graduate this year and has been beaten by his tutor for five years. His attributes have been added with several anti-fooling points, so it is not so easy to be surging. Get up.

Just listen to Senior Brother Liu say: "CRISPR is a common short palindromic repeat sequence combination that exists in bacterial DNA sequences. There may be hundreds or thousands of proteins that this gene can be transcribed into. How do we determine the precise location? Which protein can cut gene fragments?
And many of these proteins have not been discovered by us humans. If the protein that can cut genes happens to be one that has not yet been discovered, wouldn't the probability of success of this experiment be very slim? "

"Then we can only try one by one. Today is the 3rd, right? Then let's try CRISPR-Cas3 first." Zhang Wei said.

CRISPR-Cas3 stands for CRISPR-related protein 3 and is one of the many proteins transcribed by CRISPR.

The one that has the function of genetic scissors is CRISPR-Cas9, which is protein 9.

Of course it is impossible for Zhang Wei to let everyone experiment with Cas9 from the beginning. There are hundreds of thousands of proteins, and the probability of successfully finding genetic scissors from the beginning is almost non-existent. Even a fool will think there is something wrong with it.

So Zhang Wei thought about making two proteins that do not have the function of genetic scissors, and then find any excuses, such as tomorrow is September, the nine-turn large intestine in the cafeteria has not been cleaned, the birthday of an autistic person is September, etc. Let’s do the Cas9 experiment again.

In fact, in addition to CRISPR-Cas9, there are many proteins that also have the effect of genetic scissors, such as CRISPR-Cas12i and CRISPR-Cas12j, which are the genetic scissors discovered by the Chinese scientific research team and are also patented by the Chinese themselves.

……

The research on CRISPR-Cas3 turned out to be fruitless.

Zhang Wei was not discouraged, but spent his own money to treat everyone to Pizza Hut, which was considered his first team building.

After all, it was 2005 at that time, and Pizza Hut was still a fashionable and high-end consumer product. If young people could go to Pizza Hut to celebrate their birthday, they could take a photo and show it off in QQ space.

When checking out, Zhang Wei looked at the bill and then said: "Today, we spent more than 6, and 6 is a good number. Let's do it. Starting tomorrow, we will do CRISPR-Cas!"

Everyone stared at each other with big eyes and small eyes.

What's going on? Didn’t we just have a meal and spend 6 yuan? Why did you decide to do Cas4? No need for Cas5 and Cas?
This is a scientific research project! Is it so casual?
Why do I feel like the person in charge of this project is completely unreliable?

Could this project be unreliable?
(End of this chapter)

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