Re: how are downstream regulators identified?

Hi Emily,

So downstream regulators are just that - regulators. You asked if 
identifying a downstream regulator was the same process as identifying a 
regulator, and the answer is yes because they are exactly the same thing. 

The question now is, what is a downstream regulator versus an upstream 
regulator.  This is all a matter of relativity and not the kind Einstein 
was talking of! 

Let's say you have a pathway of 5 proteins A-E and a drug which inhibits 
the protein C.  So you'll have:
A --> B --> C --> D --> E.

A is upstream of B, B is upstream of C. E is downstream of A,B,C and D.  
So downstream regulators all depend on which protein or gene you are 
referring to.  If a drug inhibits C and the inhibition leads to a result, 
like cell death, or cells stop growing (cell arrest) or DNA doesn't 
replicate, etc., then we can say that C is a part of this process.

Now from C, the question is, what is upstream of C and what is downstream 
of C. From our model, upstream regulators of C are A and B. Downstream 
regulators of C are D and E.

So whenver you are faced with a scientific question, looking into the 
literature is always the best place to start. Somewhere and sometime 
another person has identified genes or proteins that work in a pathway, 
maybe the pathway you see your drug working in and your result may either 
duplicate that or implicate known genes in that pathway. It would then be 
the next experiments to see which genes either block the drug or have the 
same effect as the drug. This process of identifying factors both up and 
down stream is called epistasis.  [Mod.: In classical genetics, "epistatic" is 
used to describe "upstream of" and "hypostatic" to describe "downstream of".]

In yeast you have the ability of using genetics. There are yeast strains 
which carry mutants in all sorts of genes. This information is crucial 
for any process as well as planning out the experiments to address your 
problem at hand.

I hope this helped answer your question