Biotech Values

[poorgradstudent]

ARQL / MET:

I looked at both papers, the one Iwfal cited and the one you cited. I didn't see anything in supplemental data to exclude what Iwfal stated, or what I postulated. Rather than making a general dismissal, why don't you cite the specific part of supplemental data where the author's claims can be unambiguously shown.

The primer sequences are in the supplemental data. You just need to click on the links to the supplemental data and the primers are listed clear as day. I'm not sure what more I can do.

That may well be true, but we aren't looking at by and large, Iwfal asked about the specific cell line TOV-112D, not the general mutations found in tumors.

I'm quite sure Clark is talking about known / possible mutations of Met that may or may not be expressed in this cell line that would cause the Met to remain undetected due to the methods used.

Unless he indicates otherwise, I'm rather sure he's not asking us to dream up a scenario where we can invent a Met mutant that would not be detected by the methods used. I think he wants reasonable examples that would confound the presented data, rather than have us dream up fictional Met proteins that would confound the presented data.

I was postulating very c-terminal deletion that would eliminate the short terminal part of MET shown in Fig 1A as the CT domain, which is c-terminal to the kinase domain

Right, which is an engineered protein and has nothing to do with reasonable Met mutations that may be expressed in this cell line. So yeah, this protein won't be detected by IP methods using antibodies against the extreme C-terminus of Met... but this protein is also not an endogenously expressed form of Met in any tissue or cell line.

I already explained how it was possible to miss the protein by Western blot AND the mRNA by PCR using a single primer. If you have other papers which more precisely characterize the TOV-112D tumor cell line, then do so rather come back with than some snide comment.

You're dreaming up of a hypothetical based on no known Met mutant that I've ever read... which is why I'm suggesting that you find an example of a Met mutant that supports your hypothetical, and I'll be on board. Clearly there can be c-terminal mutations that I'm ignorant about.

But if you're simply going to say that you can imagine and design a protein that these methods won't capture, then yes that's true. But that's not a meaningful discussion point and it's not a meaningful reason to doubt the presented data.

Finally, please see this as well.

Quite frankly, I am surprised at your comments. You need a better attitude if you ever want to go from being a poorgradstudent to a poorpostdoc.

Zing! Also argumentum ad auctoritatem.