Han Meng began editing the SHANK3 gene in rats, where the nucleotide daughter strand was not yet methylated, while the complementary parent strand contained methylated groups.

These methylations are non-mutated and have the same pairing properties as normal nucleotides in rats.

Since there is a time lag between DNA replication and methylation of the daughter strand, this gives Han Meng the opportunity to scan for mismatched bases.

In vitro cell-free systems, DNA is used as a template to mimic the genes that control transcription in the organism, which is very expensive.

Expensive precision instruments are the fixed assets of the laboratory, and these fixed assets are depreciating over time. Coupled with the consumption of various raw materials, consumables, water and electricity, five experimenters will spend tens of thousands of yuan on a day's experiments, regardless of whether they produce results or not.

As the experiment progresses, the money will burn more and more.

The scientific research budget of the central biological laboratory this year is 300 million yuan, and the first quarter has just ended, and more than 100 million yuan has been spent.

Burning money may not necessarily produce results, and the four major pits of the biochemical material ring may be like this.

The scientific research funds given by the state and the sponsorship that Shen Qi pulled outside, the five experimenters were stupid and couldn't tell the difference, what they knew was that the level of money burning in this laboratory was international-level.

Huahan Gene's laboratory burns even more money, and its burn is N times that of Shen Qi's laboratory.

But there is no comparison between the labs in the university and the companies outside.

In biological research, without sufficient funds, researchers will not be able to realize their academic ideals and life dreams.

One of the most important tasks of a lab owner is to make money.

The five experimenters can understand that it is not easy for Director Shen, Director Shen is under pressure, and Director Shen has worked tirelessly in order to get more money to maintain the operation of the biological laboratory.

The Central Physics Laboratory is now breaking even, and the value of the patents they have created has recouped the cost of inputs, and there is even a small surplus.

Chemistry laboratories mainly study chemical drugs, and they have a long payback period and are now in a stage of struggle where input exceeds output.

What the center's five biological dogs can do now is to come up with some valuable research results that are widely recognized by the biological community and can create wealth as soon as possible.

Han Meng's desire to produce results was the strongest, and he calmly and meticulously operated the instrument to observe the progress of experiments at the molecular level.

"MutS recognizes mismatched bases, and MutH recognizes 2 distinct single-stranded by binding to the unmethylated 5'-GATC-3' sequence...... The effect of MutL is not obvious, but it should be the deviation caused by coordinating the activity of the other two proteins so that MutH binds near the mismatch site identified by MutS?"

Han Meng's process of doing the laboratory is also a process of continuous thinking, and there are many difficulties and puzzles in the research project of rat IQ genes.

To solve the difficult problems and solve the puzzles, the experimenters need to sum up the experience from a large amount of experimental data and keenly discover the key key.

If one path doesn't work, try another one.

The same mismatch editing method was adopted, but Han Meng's editing path was adjusted. He controls MutH to sever the G-base 5' phosphate bond attached to the methylation sequence, and the DNA helicase then unwinds the double strand, which is then degraded by the exonuclease to the exposed single strand, all the way downstream to the mismatch site.

The other four brothers tried different lines of experimentation using different editing methods, supplemented by computer analysis, and each came up with a preliminary plan that they thought was feasible.

Whether it really works or not, you need to invite the rat to appear.

Rats are rats, and Shen Qi's team raised Wistar rats, which are the most widely used in animal experiments.

The breeding house is next door to the biological laboratory, where the temperature and humidity are constant, there is food and drink, and the living conditions and quality of life of the rats are maintained at a high level.

Wistar females are fierce during lactation and often bite the hand that is put into the cage when the staff feeds them.

Normally, these rats are docile and can be kept in large numbers in a single cage.

Han Meng and the other five experimenters entered the breeding room, and the rats in the smart group were ready to move, rubbing their front paws off the ground, as if making a flattering look.

The rats of the ordinary group cooed and rolled their little eyes, their little noses moved and sniffed something, and they sensed the arrival of non-similar creatures.

The stupid rats were dumbfounded, indifferent.

Everything has a spirit, and those who study animals must first understand animals.

Cui Hualin observed the rats in front of their cages, and he proposed, "Before you gene-edit them, treat them to a good meal." ”

"That's as it should be. Han Meng nodded, and then arranged for the rats to eat.

There is a national standard for the feed of experimental mice, and these rats usually eat rat feed that meets the national standard.

Although rat feed is nutritious, it has fewer flavor choices, and there are only one or two flavors to eat.

The rats' favorite food is fresh cabbage, cucumbers, apples, sunflower seeds, blackcurrants, cherries and other fruits and vegetables.

Each of the five experimenters selected a cage of rats from the common group and invited their friends to eat fresh fruits and vegetables.

The rats in the regular group were very happy when they ate the food, they jumped back and forth and let out hearty laughter.

Although it sounds like squeaks, if you look closely, you will find that the squeaks with different frequencies represent the different mood states of the rats.

"Eat, eat more. Cui Hualin continued to feed his boys fresh fruits and vegetables, he had studied and worked in biology for so many years, and he had more than one rat life.

The other four brothers have more rat lives in their hands, they do a lot of experiments with white rats, they respect these little animals, they respect life. If they had to kill the rats, they tried to dispose of them in the least painful way.

Compared with the white rats that undertook drug experiments, bacterial experiments, virus experiments, radioactivity experiments, and pathological experiments, these white rats used for IQ gene experiments hardly felt pain in their short lives.

"Have you eaten well?" Han Meng asked the little friend in the cage.

The friends replied: "Squeak!"

"So let's start experimenting?"

"Squeak!"

"Thank you for your understanding and for your cooperation. ”

The five experimenters invited their little friends out of the cage and moved to the biology lab next door.

The rats were anesthetized on the bench, and then the experimenters operated the gene editing equipment to edit the SHANK3 gene on the rats.

According to the experimental protocol he obtained in the cell-free system in vitro, Han Meng conducted biological experiments on the laboratory mice he selected.

"Identifying Target Base ......"

"Cut non-methylated strand ......"

"Correcting Mismatched Base ......"

The experiment went well.

The rats were subjected to SHANK3 gene editing while they were sleeping.

"I'm done. ”

"I'm done. ”

Next, let's hope for a miracle to happen. ”

I just want to be a quiet student

I just want to be a quiet student