Science:
- microRNA and the Nobel prize. Link here. Another Rosalind = Nobel Prize story.
- two men were awarded the Nobel prize. As many as three can be named for any one Nobel prize. There was "room" for a third. The 1993 article was the "key" article that led to the discovery. The lead author of that article was a woman named Rosalind.
The linked article is an interview with Victor Ambros.
The microRNA story: tiny genes that turn genes on and off.
The paper that won "them" the prize: published in 1993. That's 31 years ago.
Organism: C. elegans, "a model organism for animal development."
Original research: following up mutations to find what gene was mutated and what the "new" gene product was.
By they, it was well understood that proteins could mediate changes in gene expression as cells differentiate, divide.
Researchers came across a small piece of nucleic acid that is:
- non-coding; but,
- regulates expression of other genes.
Pure luck, pure serendipity:
- researchers were not looking for the involvement of any sort of unexpected kind of molecular mechanisms.
- the fact that the microRNA was the product of this gene that was regulating this other gene in this context was a complete surprise
- there was no reason to postulate that there should be such regulators of gene expression.
- this is one of those examples where the expectations are that you're going to find out about more complexity and nuance about mechanisms that we already know about.
I assume we now have this, another triad:
- histones
- homebox / hox genes
- microRNA
So, they come across a mutant gene which they are trying to understand and it becomes frustrating. Sometimes the product of that mutant gene is plentiful; other times hard to find.
MicroRNA: a family of molecules (bits of nucleic acid) that helps cells control the kinds and amounts of proteins they make.
Reminder,
before:
- DNA --> mRNA --> protein (gene expression) --> anatomy, physiology of all organisms
- nucleic acid --> nucleic acid --> protein
- software --> software --> usable product
now:
- DNA --> <-- micro RNA --> mRNA --> amount and kind of protein (gene expression) --> anatomy, physiology of all organisms
- nucleic acid --> <-- small bit of nucleic acid --> RNA --> protein
- firmware --> <--"a macro" (?) --> software --> usable product
or is this closer:
- DNA --> mRNA --> micro RNA --> protein (gene expression) --> amount and kind of protein even as the cell is dividing / differentiating --> anatomy, physiology of all organisms
- nucleic acid --> nucleic acid --> protein --> small bit of nucleic acid protein --> determine type and amount of specific protein
- firmware --> software --> "a tweak" --> a change in the usable product
Biography of C. Elegans at the link.
- has only a thousand cells;
- all cells can be seen through a simple microscope in the living animal; but it has:
- skin, muscles, a brain, a sensory system, intestine, complex behavior
One can study those cells as they divide and differentiate during development.
The researchers working in the trenches in that lab, two women:
- Rosalind Lee -- lead author of the 1993 paper
- Rhonda Feinbaum
The surprise: the pieces of DNA (sic) that were sufficient to confer the function of this gene and rescue a mutant were really small, only 800 base pairs.
So, this suggested that the gene is small, so the product of this gene is going to be pretty small.
Rosalind worked to pare down the sequence more and to mutate potential protein coding sequences in that little pice of DNA (sic).
By a process of elimination, she finally showed that there was no protein that could be expressed from this gene!
At the same time, we identified this very, very small transcript of only 22 nucleotides! This was the microRNA!
Transcript -- transcription: DNA --> mRNA --
There was probably a period of a week or two there where these realizations came to the fore and we knew we had something new.
The rest of the story at the link.
lin-14: link here.
L1:
No comments:
Post a Comment