Yeast Research at North Central College


Yeast as a Model Eukaryote
[Buds]

Baker's yeast (Saccharomyces cerevisiae) is a single celled eukaryotic fungus that is commonly used as a model organism.  There are many reasons that yeast is a favorite eukaryote to study: yeast are easy to grow, nonpathogenic, easy to transform with DNA, easy to mate, stable as both a haploid and a diploid and recombination happens frequently.  Additionally, yeast has been highly studied yielding a lot of background (over 53,000 scientific papers in the last 40 years) and the DNA sequence of the entire genome has been available since 1996.  From this sequence, we know that yeast has just 6,145 genes (compared to 30,000 - 150,000 genes in humans).  Despite the large number of papers published on my favorite organism, only just over half of the genes have been studied so far, leaving plenty of work to be done.  For more information on yeast as a model eukaryote, see Fred Sherman's excellent review article, An Introduction to the Genetics and Molecular Biology of the Yeast Saccharomyces cerevisiae.

    The RAS Signal Transduction Pathway and Yak1

Ras is one of the most commonly mutated genes in human cancers.  It is estimated that up to one third of all cancer contain mutations that activate the Ras gene and that this activated Ras gene contributes to the formation of the cancer.  Ras acts as a molecular switch; when Ras is 'on' it tells the cell to grow and divide.  S. cerevisiae also has a Ras gene that functions similarly to the human gene (indeed, if one replaces the yeast gene with the human gene, the human gene works just fine in yeast).  Therefore, we can learn more about how the Ras protein functions in people by studying the Ras protein in yeast.  

How does the Ras protein transmit the "grow" signal into the cell?  It relays the information through a series of proteins and small molecules in an arrangement referred to as a signal transduction pathway.  The Yak1 protein is a part of this pathway.  Yak1 is a protein kinase, which means that it enzymatically attaches phosphates to other proteins and that these modifications will change the functions of the target proteins.  However, Yak1 activity opposes the Ras signal. Therefore, activated Yak1p sends a "don't grow" signal and the loss of Yak1p enhances growth.  Precisely how Yak1 inhibits growth remains unknown but is a topic of great interest.

MSI1 suppresses the RAS Signal Transduction Pathway

Msi1p is another yeast protein that can also suppress the RAS pathway in yeast.  More than 15 years ago, it was discovered that extra copies of could turn off this pathway but the mechanism by which MSI1 works has remained elusive to this day.  Strangely, Msi1p seems to do other things in the cell too, including wrapping newly synthesized DNA around structural proteins and turing RNA synthesis on and off.  Because it is such a surprise, it makes an interesting project to pursue.  We have previously discovered that Msi1p appears to affect the RAS pathway by blocking the function of the Npr1p kinase.  

Both Yak1p and Msi1p (through Npr1p) deactivate the RAS pathway by unknown mechanisms.  Could these two proteins both be using the same means to affect RAS?  That might well be the case and could help us understand both of them.  In our recent Journal of Molecular Biology paper, we show that Msi1p and Yak1p cooperate on several activites.  For example, extra copies of Yak1p slow cell growth, but only if Msi1p is present in the cell.  Similarly, the presence of Yak1p promotes the accumulation of Msi1p in the nucleus when the cell is consuming sub-optimal food sources.  

So how do these three genes connect to RAS?  That is the current focus of the Yeast Lab.  We are in the process of identifying yeast genes that either cooperate or inhibit the ability of Yak1p/Msi1p to slow growth as we expect this to lead us to the direct connection to the RAS pathway.

MSI1 and Transcription

 

As if we didn't have enough mysteries, Msi1p can activate and repress the transcription of certain genes.  However, it only does so under specific physiological conditions.  The Yeast Lab has identified certain carbohydrates that induce transcription and certain carbohydrates that are noninducing.  Our lab is currently in the process of identifying (i) what yeast genes and pathways are needed for these carbohydrates to affect Msi1p and (ii) the precise mechanism by which Msi1p alters transcription.  We recently presented our findings in a poster at the 2006 Yeast Genetics and Molecular Biology Meeting in Princeton.  

Student Researchers Needed!

Are you a North Central College student interested in conducting a research project in the Yeast Lab?  There are currently a variety of projects available.  Much of our research is done during the summer, but there are students who also working during the school year.  If interested, stop by to see Dr. Johnston in the Science Center.
Return to Dr. Johnston's Homepage

Pictures of the People in the Yeast Lab


Last updated: March 26, 2007
Comments about the content of this page should be sent to: sdjohnston@noctrl.edu
Copyright 2007, North Central College