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Synthetitic genetic screening in yeast

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Synthetitic genetic screening in yeast

Postby nukeman » Mon Sep 10, 2012 5:57 pm

Hi,

The concept of Synthetic-lethality and Synthetic Genetic Array have been introduced to us in class recently, but I'm struggling with understanding it. Quite frankly, I don't even understand what questions one is seeking answer to using these techniques.

I was given some papers to read up on so that I could better understand, but all I see is mumbo-jumbo (I'm attending basic level courses so most scientific articles are quite hard for me to understand fully).

Furthermore, what exactly is one doing in practical terms when dealing with Synthetic-lethality & Synthetic Genetic Arrays?

The only thing I get is that you use genetic deletions to study how different genes can perform tasks that are ordinarily assigned to other genes if a situation should arise when the primary gene is not viable.

I would appreciate it greatly if someone could simplify this for me. Thanks.
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Postby Cat » Mon Sep 10, 2012 6:51 pm

To really simplify:

Say you have a car that came with a car key AND separate alarm button that can open car door. In that case, you have 2 ways to get into a car: with a key OR with a button. They are totally different as in case of the alarm button you cannot turn on the car. So, if you were to lose the key, you can still get into a car but not drive it (let's call it a different phenotype). Let's for purposes of analogy also equate being unable to access the car with lethal phenotype (as car is useless). Now, in this situation you need to lose BOTH key and alarm button to get "lethal" phenotype...

People create mutants in one gene with mild phenotype (like loss of a key in the above example) and then look for the other mutation that would result in lethal phenotype when combined with it. It allows do see different ways the cell has available to achieve the same end result.
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Postby nukeman » Tue Sep 11, 2012 4:22 pm

I think I see what you mean.

I talked with my teacher briefly today, and he said that simply what you do is, you run for example 100 genes. You start by mutating gene 1 and then mutating gene 2, then you proceed with mutating gene 1 again, but this time you run it with a mutated gene 3.
If you know that gene 1 partakes in a specific transcription process, and if that particular process ceases to function when the host has been double mutated in genes 1+3 (example), then that means that gene 3 is probably involved in that same process because if only gene 1 was mutated, then perhaps gene 3 could have "covered" for it at least partially.

Have I understood this correctly? Also I'm somewhat confused as to what type of mutation this involves, is it simply deletion or something else? Also, why would there be 2 genes that do the same thing? Could this mean that they simply share intermediate steps and so can complement each other without necessarily leading to the same end product?
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Postby Cat » Thu Sep 13, 2012 1:49 am

Your explanation seems to be correct. The type of mutation used depends on the phenotype. If it's mild (I mean for deletion), then deletion is used. If it's severe, then substituting normal promoter for the inducible one (one that you control) is used...

As to two genes doing "the same thing", they are not doing the same thing at the molecular level. They could have additional functions but they also to be involved in the same process (with the same end product) to save oganism from death.
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Re: Synthetitic genetic screening in yeast

Postby nukeman » Mon Sep 17, 2012 9:48 am

I understand, thank you very much for the clarifications.
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