New & Noteworthy
December 5, 2012
Thank you for your patience during our move to the new data center last week.
This move is very significant for us, as we are now in a professionally managed computing facility with all the necessary backup cooling and power contingencies available. This move also allows us to continue expanding our services.
The computer room is critical for the stability of SGD and other resources. Our previous location was created when SGD was young, and did not accommodate the amount of growth we have enjoyed. We are very happy to have the opportunity to be located in this brand new facility designed for research computing.
November 21, 2012
Many SGD tools and resources will be unavailable from Tuesday afternoon, November 27th, until Thursday, November 29th because we will be moving all of our servers to a new data center. This new data center will provide a more secure facility, a faster network, and a diesel generator to provide electricity in the event of a power failure.
You will be able to search the main SGD database during this time. However, many tools and pages, including the following, will be unavailable: Pathway Tools, YeastMine, Downloads/FTP, SPELL, GBrowse, Textpresso, and the SGD Wiki.
We apologize for the inconvenience and thank you for your patience.
Please contact us at firstname.lastname@example.org if you have any questions or concerns.
November 19, 2012
A study by Blasco and coworkers confirms that beer foam is littered with corpses of dead yeast. Or at least with bits of their cell walls.
This has been known for awhile. But what these researchers did was to identify one of the key proteins in the cell wall important for maintaining a good head on beer.
The authors knew from previous studies that certain mannose binding proteins play an important role in beer foam. So they used primers that lined up with the 5’ and 3’ ends of one of the known foam-related genes from S. cerevisiae, AWA1, to look for similar genes in the brewing yeast S. pastorianus. This allowed them to PCR out the CFG1 gene.
To show that this protein was involved in the foaminess of beer, they next knocked the gene out of S. pastorianus and used this deletion strain to do some brewing. What they found was that while beer made with this strain had about the same amount of foam, it didn’t last as long. This strongly suggested that CFG1 was involved in maintaining a good head on a mug of beer, earning the gene its name: Carlsbergensis Foaming Gene.
As a final experiment, they added the gene back to a strain of S. cerevisiae, M12B, that makes beer without foam. When this strain expressed CFG1 and was used to brew up some beer, that beer was foamless no more. This suggests that CFG1 may be important for foam formation as well as stabilization.
What is probably happening is that during fermentation, yeast cells are autolysing, releasing their cell wall proteins into the beer. Since Cfg1p is hydrophilic on one end and hydrophobic on the other, it forms very stable bubbles. And foam is simply a bunch of stable bubbles.
Hopefully scientists can use this information to tweak the amount of foam a given beer yields. Then a drinker can choose lots or little foam, long lasting or short lived foam, or any combination he or she wants.
Root beer foams for a different reason
November 8, 2012
One of the many stumbling blocks in finding better treatments for genetic diseases is figuring out the cause of the disease. These days, this doesn’t necessarily mean simply identifying the gene with the mutation. No, nowadays it can mean figuring out what each specific mutation does to the gene it damages.
See, many genetic diseases are not caused by single mutations. Instead, lots of different mutations can all damage the same gene in different ways. And each class of mutation may require different treatments.
Cystic fibrosis (CF) is a great example of this. While most cases of this ultimately fatal disease are caused by mutations in the CFTR gene, not every mutation does the same thing to the CFTR protein. Because of this, scientists have found different drugs to treat people with different classes of CFTR mutations.
So one drug, Ivacaftor, targets CFTR proteins that can’t open up as well as they should, while another investigative drug, PTC124, targets prematurely stopped CFTR proteins. Each only treats a specific subset of CF patients who have the correct CFTR mutation.
All of this screams out for a quick and easy assay to figure out how a mutation actually disables a certain protein. And this is where a new study by Pittman and coworkers just published in the journal GENETICS can help.
The authors have come up with a sensitive in vivo assay in S. cerevisiae that allows scientists to quickly identify mutations that lead to unstable proteins. This kind of instability isn’t rare in human disease either. Some of the more famous examples include a kidney disease called primary hyperoxaluria type 1 (PH1), Lou Gehrig’s disease (ALS), Parkinson’s disease, spinal muscular atrophy (SMA), and even some forms of cancer.
The assay basically inserts wild type and mutant versions of the gene of interest into the middle of the mouse dihydrofolate reductase (DHFR) gene, individually adds these chimeric genes to yeast lacking DHFR, and then measures growth rates. The idea is that if the mutation leads to instability, the DHFR chimeric protein will be unstable too and the yeast will show growth defects under certain conditions. This is just what they found.
Initially they focused on a gene involved in PH1, the AGT gene encoding alanine: glyoxylate aminotransferase. They were able to show that disease causing mutations known to affect protein stability affected growth in this assay. Not only that, but there was a strong correlation between growth and level of protein stability. In other words, the more unstable the protein, the more severe the growth defect.
They then expanded their assay beyond known AGT mutations. First they were able to identify a subset of disease-causing AGT mutations as affecting the stability of the AGT protein. But the assay ran into trouble when they switched to the more stable SOD1 protein. This protein, which is involved in most cases of ALS, is so stable that mutations that destabilized it were invisible in the assay. The authors solved this problem by introducing a mutation into DHFR that destabilized it. Now they could identify mutants that destabilized SOD1.
As a final step, they used their assay to screen a library of stabilizing compounds to identify those that specifically stabilized their mutant proteins. Unfortunately, in this first attempt they only found compounds that stabilize DHFR, but the assay has the potential to find drugs that stabilize disease-related proteins as well.
Whether or not that potential is realized, this technique should still be a very useful way to determine whether a mutation affects protein stability. Then, when drugs that stabilize the protein have been found, using this or other screens, doctors will know which patients can be helped by these compounds. And this will be a boon for scientists and patients alike.