Leveraging proteomics to develop an accurate model system for human fallopian tubes!

 

We've eventually got to get away from animal models for human studies. There are clearly dramatic differences between mouse/rat/nematode/yeast biology and human that lead to all sorts of false discoveries. These are so drastic that some funding agencies have rapidly approaching hard deadlines where they just won't fund the stuff.

But human biology is tough to mimic in a bioreactor, even if those things are increasingly inexpensive and easier to use. Even modeling something as relatively "simple" as the blood brain barrier is not at all simple. How the f(ourier) do you model something as important and complex (and amazingly under-studied) as the human fallopian tubes??? 

Like this! 

 Okay - so one way you could do this would be to get some human donor samples and do some really amazing imaging and then dig deep through previously deposited data to help construct yourself a map. (P.S. I love that the authors did such a nice shoutout to my long time neigbors in the JHU Microscopy Core.) Could you do a lot better? What if you also captured physiological function like oocyte transport?!? Could you end up with a map that provided a dynamic understanding of how the system changes during physiological function? That would help as well, but what if you used that information to build the most accurate in vitro system for studying these tissues as you could? This multi-institute team did something like all of this. Cells were grown out to organoids which were coaxed into "assembloids" (we're far outside of my expertise here, so please forgive my interpretations) and by controlling the matrices and how these cells were coaxed do differentiate and assemble, they get there. Proteomics was used along the way (TIMSTOF HT with EvoSep One, diaPASEF, analysis with SpectroNaut) to verify that the system proteome expression profiles.

Even for someone (me) who couldn't follow a lot of the biology/cell differentiation stuff, this is clearly an exciting work. I'd 1,000x prefer having access to engineered systems for my pharmacology work over mouse models. Up that another 1,000x if I those systems were backed up with proteomic data that they were accurately representing human biology.