New & Noteworthy

Apply Now for the CSHL Yeast Genetics & Genomics Course

March 31, 2014

For more than 40 years, the legendary Yeast Genetics & Genomics course has been taught each summer at Cold Spring Harbor Laboratory. (OK, the name didn’t include “Genomics” in the beginning…) The list of people who have taken the course reads like a Who’s Who of yeast research, including many of today’s leading scientists and two Nobel laureates (Randy Schekman in 1975 and Jim Rothman in 1985, who both won the 2013 Nobel Prize). 

Now it’s your chance to attend this summer course (July 22 – August 11) and get a comprehensive education in all things yeast, from classical genetics through up-to-the-minute genomics and the latest cytological techniques. Scientists who aren’t part of large, well-known yeast labs are especially encouraged to apply – for example, professors and instructors who want to incorporate yeast into their undergraduate genetics classrooms; scientists who want to transition from mathematical, computational, or engineering disciplines into bench science; and researchers from small labs or institutions where it would otherwise be difficult to learn the fundamentals of yeast genetics and genomics.

Besides its scientific content, the fun and camaraderie at the course is also legendary. In between all the hard work there are late-night chats at the bar and swimming at the beach. There’s a fierce competition between students at the various CSHL courses in the Plate Race, which is a relay in which teams have to carry stacks of 40 Petri dishes (used, of course).

The application deadline is April 15th, so don’t miss your chance! Find all the details here.

Silly Sod’s Two Jobs

March 27, 2014

Most SGD users are probably too young to remember Saturday Night Live’s early years.  One very funny commercial parody involved Gilda Radner and Dan Aykroyd arguing over a product called Shimmer.  Gilda argues that it is a floor wax while Dan says it is a dessert topping.  In comes Chevy Chase to tell them that it is both.  Not quite as funny as Bassomatic, but still hilarious.

In a new study, Tsang and coworkers show something similar for the enzyme Sod1p.  Most people know Sod1p as an enzyme that protects the cell and its DNA by directly deactivating harmful reactive oxygen species (ROS) like superoxide.  Turns out that it may also be a transcription factor.

Now these two jobs aren’t quite as disconnected as a dessert topping and floor wax.  When Sod1p acts as a transcription factor, it is regulating genes that affect a cell’s response to ROS.  It is actually using its two functions to attack the same problem on multiple fronts.

Tsang and coworkers started out by looking at what happens to nuclear DNA under oxidative stress, using the Comet and TUNEL DNA damage assays. They found that endogenous and exogenous ROS caused DNA damage that was much worse in the sod1 null mutant – in other words, Sod1p protected the cells’ DNA. Using immunofluorescence, they also showed that Sod1p quickly went into the nucleus in the presence of ROS.  But if they restricted Sod1p to the cytoplasm by adding a nuclear export signal, the protein no longer protected the DNA.  In fact, it did no better than a strain deleted for SOD1.

In the course of these experiments one of the ways the researchers induced nuclear localization was with a burst of hydrogen peroxide.  But since hydrogen peroxide isn’t a substrate of the enzyme Sod1p, Tsang and coworkers next wanted to figure out how Sod1p got its signal to go nuclear.

Previous work had shown that SOD1 genetically interacted with MEC1, a yeast homolog of ATM kinases which sense oxidative stress.  They deleted MEC1 and found that Sod1p was trapped in the cytoplasm, unable to protect the cell’s DNA from damage.  This result was confirmed in human cells by showing that Sod1p only went nuclear if the cell made ATM kinase.

Tsang and coworkers suspected that this interaction might happen through a protein kinase called Dun1p, whose human homolog is a Mec effector. They confirmed a previous mass spectrometry result that showed Sod1p interacted physically with Dun1p.  And indeed, when DUN1 was deleted, Sod1p was again stranded in the cytoplasm.  Further work showed that Dun1p does its job by phosphorylating Sod1p on two serine residues, S60 and S99. When both these serines are mutated to alanine, preventing phosphorylation, less of the mutant Sod1p makes it into the nucleus. 

Using DNA microarrays, Tsang and coworkers next showed that SOD1 was required to activate 123 genes needed by the cell to respond to hydrogen peroxide.  These genes fell into five categories: oxidative stress, replication stress, DNA damage response, general stress response and Cu/Fe homeostasis.  The final experiment used chromosomal immunoprecipitation (ChIP) to show that in the presence of hydrogen peroxide more Sod1p was bound at the promoters of two of these genes, RNR3 and GRE2, but not the control gene ACT1. 

Of course, the authors have only looked at two of the 123 genes and an obvious next step is to figure out how many of the 123 have more Sod1p bound to their promoters in the presence of hydrogen peroxide.  Still, if these results can be confirmed and expanded they will suggest that Sod1p is able to combat oxidative damage in two completely different ways. 

In the first it uses its enzymatic activity to directly inactivate the ROS superoxide, while in the second it helps the cell respond to other ROS apparently by acting as a transcription factor.  While the jobs themselves are not as different as a floor wax and a dessert topping, how Sod1p goes about getting each job done is.  “Calm down you two, Sod1p is an enzyme AND a transcription factor.”

In addition to these two roles, we’ve written before about yet another regulatory role for Sod1p: it regulates glucose repression by binding to two kinases and stabilizing them. This is truly an overachiever of a protein!

by D. Barry Starr, Ph.D., Director of Outreach Activities, Stanford Genetics

Explore a Large New Chemogenomics Dataset Via SGD

March 26, 2014

What happens when you cross two comprehensive deletion mutant collections with a library of more than 1800 structurally diverse chemicals? HIP HOP happens. Not the music, but a whole lot of very informative phenotype data – over 40 million data points!

The response of S. cerevisiae mutant strains to a chemical can tell us a lot about which pathways or processes the chemical affects. This is not only interesting for yeast biologists, but also has important implications for human molecular biology and disease research. So a group at The Novartis Institutes of Biomedical Research decided to test the sensitivity of nearly 6,000 mutant yeast strains to a panel of about 1,800 compounds. 

Hoepfner and colleagues have published these results and have also generously offered them to SGD.  They used the HIP and HOP methods (HIP, HaploInsufficiency Profiling, using diploid heterozygous deletion mutant strains; HOP, HOmozygous deletion Profiling, using diploid homozygous deletion mutant strains) that have proven very useful in yeast since the creation of the systematic deletion mutant collections.

To do this mammoth series of experiments they obviously needed to set up an automated pipeline. These sorts of experiments have been done before, but in this study Hoepfner et al. improved on existing procedures in many ways: the physical techniques, the controls and replicates included, and the methods for data analysis.

Phenotype annotations in SGD. We’ve incorporated a subset of these results into SGD as mutant phenotype annotations. Why a subset? Some of the chemicals that were used in these experiments are un-named proprietary compounds, so the individual phenotypes would not be very informative in the context of SGD. We’ve added the phenotypes that involve named chemicals to SGD – more than 5,500 annotations. These may be viewed on Phenotype Details pages for individual genes (see example), retrieved as a set using Yeastmine, or downloaded along with all SGD mutant phenotype annotations in our phenotype data download file.

Easy access to the full dataset and analyses. We’ve also added a new set of links to SGD that take you directly from your favorite gene to the authors’ website, which provides full access to all of the data and interesting ways to look at it (see below). When you click on a “HIP HOP Profile” link from the Locus Summary page or the Phenotype Details page of a gene in SGD, the landing page at the authors’ website allows you to explore data for mutants in that gene or for chemicals affecting that mutant strain. You can see which chemicals had the greatest effects, which other mutant strains have a similar range of phenotypes, and much more. And if a chemical that has interesting effects is proprietary, don’t worry; Hoepfner and colleagues have stated that they “encourage future academic collaborations around individual compounds used in this study.”

Information about mutant strains. In the course of this study, the authors also generated some very useful data about particular mutant strains in the deletion collection. Some of them were hypersensitive to more than 100 different chemicals. Others turned out to be carrying additional background mutations that could affect the phenotypes of the mutant strain. We are planning to display this kind of information (from this and other studies) directly on SGD Phenotype Details pages in the future.

We thank Dominic Hoepfner and colleagues for sharing these data with SGD and for helping us to incorporate the data.  And we encourage you to explore this new resource and contact us with any questions or suggestions.

Yeast Genetics Meeting Abstract and Registration Sites Now Open

March 24, 2014

The 2014 Yeast Genetics Meeting will be held July 29 – August 3 at the University of Washington, Seattle, Washington. Abstract submission and registration sites are now open.  The abstract submission deadline is April 24.   Be sure to get your abstract in by the deadline so that it will be programmed and included in the Program Book.*

The Genetics Society of America is pleased to announce the following awards and lectures will be presented:

• George Church, Harvard University – Lee Hartwell Lecture
• Olga Troyanskya, Princeton University – Ira Herskowitz Award
• Jeremy Thorner, University of California, Berkeley – Lifetime Achievement Award
• Anita Hopper, Ohio State University – Winge-Lindegren Address

In addition, there will be two special presentations: Jon Lorsch, Director of the National Institute of General Medical Sciences, NIH will discuss the future plans of the Institute and Gerry Fink, MIT, will give a retrospective look at Fred Sherman’s life and his impact on the field of yeast genetics research.

As usual, SGD staff will be at the meeting and we look forward to meeting and talking with yeast researchers. Don’t miss this premier conference of the yeast community!

*IMPORTANT NOTE: NEW THIS YEAR: The full text of all abstracts submitted by the deadline date will ONLY be available online, as a pdf and in the abstract search program,  and will not be printed in the program book. The program book will still contain the full schedule information including platform and poster sessions date, time, title, authors, gene index and a listing of exhibits. Late abstracts will only be accepted if space permits and will not be included in the online search.

Questions? Contact Anne Marie Mahoney: mahoney@genetics-gsa.org