National Nature III - Design of basic research topics in clinical diseases: cell model and detection indicators

Last time we said that the basic research topic of clinical research, how to design the content of genetic research. Three major blocks, clinical relevance (AC), function (AD), and mechanism (AB). This confirms our hypothesis that "A gene plays a D function in C disease by regulating B mechanism."

A question remains, how to choose the cell model (animal model) and test indicators. The rigor (depth) and heat of the mechanism (the direction of the mechanism subdivision) is the place of the research level of the subject, and the last time did not say that it is necessary to talk alone. I have taken out the cell model and the detection indicators alone, why? Because this is a scientific place to evaluate the subject.

In the history of disease research, according to the requirements of current scientific research, the finer the better, once the clinical manifestations of the disease determine which organ tissue is a problem, we go to the organ tissue to find the cause. The smallest functional unit of organ tissue is the cell. Then ask, what cells are different from normal cells, which leads to problems in organ tissues and eventually clinical manifestations. The difference here is the pathological change. The pathology and laboratory of the hospital do it every day. (If you want to take out the treasure map and worry about your aesthetic fatigue, you won’t take it. The unclear package is moved to the previous reference.)

At the cellular level, we have to consider three questions , 1, who. 2, how is different from normal (pathological changes - detection indicators). 3. Can I do it (feasibility)? The first two are scientific assessments, the latter one is related to our lifetime scientific career.

1. Who?

Dig a disease organization and ask, is there only one type of cell or a multi-type cell? Do not think that this issue is very naive. Many years ago, many scientists decided that tumors were homogeneous tissues. Now everyone knows that tumors are heterogeneous.

I think if you can see this article from the first national nature article, then your answer is definitely many. Then ask another question, is my class designed to write multiple classes or one class?

If your answer is to write multiple classes, then the return opinion is often that the project design does not aggregate. Because our experiments on the cell are to verify whether the A gene or drug we are studying can cause pathological changes on the cell or play a role in relieving pathological changes. The same gene, in different cell types, may function differently and the mechanism may be different. The current topic is about depth, not breadth. The current research is generally concentrated at one point and deep digging. The deeper the better.

I don't know if there is a package against this view. Because, nowadays, CART is very popular in the field of cancer treatment. If you are still involved in a class of cells, CART research is wrong. why. Because this type of research is to study the killing effect of immune cells on tumor cells, the relationship between the two types of cells is studied (immune cells are not a type of cells, and immune cells must be clearly defined as immune cells). The subject of studying the relationship between cells and the types of cells involved in the relationship must be designed.

In the past few years, many people have been planting their heads. They should only put one type of cells and put them in multiple categories. In recent years, there have been many research topics, and many people have only designed a class of cells.

When designing a topic, ask yourself, I am studying the function of the A gene or drug in a class of cells, or the function of the cell. Who is the cell model ?

2, how is different from normal (pathological changes - detection indicators)

This place is actually the test indicator of our experiment. What indicators do I use to prove that the genes or drugs I have studied play a disease-related function in pathological cells?

For example, I am doing epilepsy research. The pathogenesis organs and tissues of epilepsy are brain brain tissues. Cells are brain neurons. OK, my design is, "I hypothesized that genes associated with epilepsy, after interference or overexpression in brain neurons, detect MTT growth curves, flow detection cycles change, and flow detection of apoptosis changes." Is this design OK? We usually read articles, and many articles are doing this. Evaluate whether the designed test indicators are OK. The scientific assessment is based on whether these test indicators are pathological changes in clinical cells. That is, whether this change occurs in such cells of a clinical patient. Epilepsy, one of the differences between a patient's brain neurons and normal human brain neurons is abnormal discharge. Abnormal discharge, on the cell, what we should do is electrophysiological testing.

At this point, the return opinion of "the experimental method is unreasonable" is saying this. "The experimental method lacks new ideas." Many teachers saw this return opinion and thought it was to design a new experiment. In fact, this point is saying that the experiment you are using is what everyone is doing now. It's OK to use an outdated method, but now you have to use the methods you use.

Cell model and test indicators, how to evaluate this place, we will break down next time.

3. Can I do it (feasibility)?

Ji Bo said that this point is related to our lifelong research career. This is not to scare you. In the research career, it is very important to get the project funding, but more importantly, I have made the project and published a high-scoring SCI article, so that everyone can recognize my research ability, and then smoothly get the next topic, there is funding. Continued research. A virtuous circle.

If the subject is designed, the cells are difficult to operate and the experiment is difficult to raise. The first-instance experts will go to see the applicant's background and see the published articles. If the published article used this cell, I have done these experiments. Then you are feasible to complete this project. (Now, the applicant country must naturally have good SCI articles. These articles are actually to prove that the applicant has the research ability and can complete the research of this project.)

In the national tender template, it is necessary to introduce what projects the applicant has undertaken and what the situation is. If I get it, but the cells are difficult to do, the experiment is difficult to do, and there is no good article. Why, on the basis of persuading the experts, I will do a good job in this project, and I will make good results.

Once you can't get the funding for the next project, how can you do the follow-up research? Unless you know Zuckerberg, it's not bad. However, if the project with feasibility is problematic, even if it is better, it is estimated that he will not invest money.

Summary, the first step in the design of clinical disease basic research topics

1. Determine the cell model (animal model) for clinical problem studies.

2. Identify indicators for assessing gene or drug function.

3. Evaluate the feasibility of the research team.

PS: I hope that friends who have more exchanges with Jibo in learning and experimentation can pay attention to Jikai Gene WeChat and reply to the words “Jibo”.

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