mouse knockout applied to ER

[mcater2006]

Dear Premed101'ers:

 

While preparing for interview yesterday I came across the following interesting question:

 

"How would some data get from a basic knockout mice experiment relate to a physician in the ER treating a patient."

 

for which I have given the following tentative answer:

 

"From what I have learned in cell and molecular biology, I know that knockout experiments consist of deleting certain genes from a mice embryo and look for phenotypic changes in the grown up mice with the knockout gene, thereby arriving at conclusions about what the gene does. One way in which I think this information will relate to physicians treating patients in ER is through proteins, which are products of genes that will do the actual biochemical work that will sustain life. I will illustrate this with an example.

 

Suppose that insulin was yet unknown to humanity. A basic knockout mice experiment that knocked out the insulin-producing gene would result in the mice suffering from diabetes. Now if a patient is admitted to the emergency room with a dangerously high level of blood sugar, then physician working in ER could use the results of the knockout mice experiment, coupled with the ability to manufacture proteins in transgenic bacteria, to inject insulin into the patient’s blood stream to lower his blood sugar, all without knowing what insulin is exactly."

 

I would like your comments on the appropriateness of my response.

 

Thanks for all your help.

 

mcater2006

[avenir001]

sounds good...but i think that question is too specific...a history major may not know what a mice knockout expt is...so it would have to be explained to him/her...i think the point of a question like this is to see whether you know how results from basic research apply to (or should apply to) clinical practice, whether you're knowledgeable about the process, have common sense, can think like a scientist, etc...so for example one could say scientists could treat the knockout diabetic mice with different drugs and see which ones are safe & effective, etc., then move to clinical trials with humans, etc., and at the end we have evidence-based medicine, which is a hot topic right now.

[A-Stark]

That doesn't sound like a very practical application. If you didn't know what insulin was, how would you be able to determine what gene to knock out? It could be an insulin receptor that's faulty, after all.

 

Anyhow, the probability of a question like that appearing in an interview is effectively zero. It's extremely specific, and the whole point of interviews is to assess your critical thinking and communication skills, as well as your sense of ethics and knowledge of the health care system - NOT to assess your scientific knowledge.

 

How are you going to create transgenic bacteria that produce insulin if you don't even know what to collect from them (like, oh, the insulin)?

[SpanishFly]

 

How are you going to create transgenic bacteria that produce insulin if you don't even know what to collect from them (like, oh, the insulin)?

 

good point, knock out expts. often are the result of some previous knowledge that supports the idea that that gene is somehow important to a particular function or pathway...it seems all I ever do these days is research transgenic mice experiments but I don't expect they'll ask such a scientific specific question.

 

having said that, there are a lot of examples that come to mind, the only thing is, none of the ones I can think of apply to emergency medicine...for instance right now I'm studying skeletal muscle differentiation and muscular dystrophy...a great application, but not something your ER doc would be dealing with...

[premedgirl]

would it be something more basic, like both are helping improve the health of patients. the ER doc in a direct way , and the mouse in an indirect way (im doing my honours project on a mouse gene knockout of a cancer gene, so in the end this info may be helpful at somepoint for treating cancer or predicting cancer)

[Vallinar]

unless your project was on knockouts (or you worked with them) i can't for the life of me see why an adcom would ask that question.

[ploughboy]

Mice? In my ER? It's more common than you'd think.

 

(obscure?)

[mbene085]

I agree that this question would never pop up - they aren't there to test your scientific knowledge. The closest thing they might ask would be, "How important do you feel the relationship between research and medicine is?" or something like that.

 

Not to mention that knocking out a gene and manufacturing/purifying proteins (or polypeptides as the case may be) is something you only do if you already have a good idea of what that gene/gene product is doing in the body. Blindly knocking out genes and synthesizing random proteins would be a total black hole for your grant money and wouldn't get you very far at all.

 

Plus, the day they let an ER doctor inject a patient with a substance when they "don't know what it is exactly" is a sad, sad, sad day for our medical system.

[EllieGee]

Blindly knocking out genes is something that's commonly done! You can order knockout mice of nearly every gene in the genome, even if it hasn't been studied before, to study it yourself. Same thing with Drosophila and prob other organisms too!

 

Just a thought

[premedgirl]

Blindly knocking out genes is something that's commonly done! You can order knockout mice of nearly every gene in the genome, even if it hasn't been studied before, to study it yourself. Same thing with Drosophila and prob other organisms too!

 

Just a thought

 

Thats what my lab does with mouse ES cells and creates the mice.

I think its definitely more of a money maker than bad for grants because people will probably buy the mice.

[EllieGee]

Some labs do huge forward genetic screens too: they just randomly mutagenize the organism, look for the phenotype they want in the mutants, and then characterize them from there!

 

Very often done in plant research Good ol' Arabidopsis!!

[mbene085]

I know that blind knockouts and loss-of-function observations are great for figuring out a gene's role.

 

I phrased it awkwardly. I was trying to say that creating knockouts and then skipping ahead to synthesizing and purifying gene products when you "don't know exactly what the protein is" isn't commonly done. You don't often get a gene product with a clear-cut role, where having the purified protein is of much value. It was more the synthesis that I meant would be a money sink...knockouts are great research tools. Having 3 grams of a purified protein with an ambiguous function might not be so useful...that's time and money that could probably have been spent more effectively elsewhere.

[rogerroger]

Keep in mind lots of KOs are embryonic lethal. If you want to really figure out what a gene does tissue specific KOs are where it is at.

 

I personally would say that KO research has identified many genes which are associated with various heart conditions. Knowing ones genetic profile could help determine treatment plans. This is were medicine is going in the future. Medications and treatments tailored to your genetic expression.

 

Choose your physiological system, KOs have played a role in understanding how it works at the molecular level.