New & Noteworthy
April 26, 2016
If you’re not already using YeastMine to answer all your questions about S. cerevisiae genes and gene products…you should be! SGD’s YeastMine is a powerful search tool that can retrieve, compare, and analyze data on thousands of genes at a time, greatly reducing the time needed to answer real, practical research questions. Through YeastMine, questions such as “What proportion of plasma membrane proteins are essential?” or “How many different gene products physically interact with the mitochondrial ribosome?” can be answered within minutes.
Next week on May 4th, 2016 at 9:30 AM PDT, we will provide a brief webinar tutorial on how to run queries and create gene lists in SGD’s YeastMine. As a practical demonstration of YeastMine, we will also showcase a research scenario in which yeast-human homology data is used to predict potential chemotherapy targets for human cancers.
Space for this webinar is limited. To reserve your spot, please register for the event using this online form: http://bit.ly/registerFor2ndSGDwebinar
This is the second episode of the SGD Webinar Series. If you missed the first one, or if you’d like to find out more about upcoming webinars, please visit our wiki page: SGD Webinar Series.
April 20, 2016
Most of us know about yeast’s big part in making bread and booze. But those aren’t yeast’s only wonderful gifts. It also plays a big role in chocolate and coffee too. Is there anything this marvelous microorganism can’t do?
A new study by Ludlow and coworkers in Current Biology set out to look at the strains involved in cacao and coffee fermentation. Unlike the extensively studied wine strains, these have mostly been ignored up until now.
These researchers found that cacao, coffee and wine strains were very much different from one another. And they also found that unlike wine yeasts, which are pretty much the same most everywhere in the world, coffee and cacao strains are different depending on where they come from.
But the cacao and coffee strains did have one thing in common. Each had a lot in common with the other strains in its country and even on its continent.
So, for example, coffee strains from all over South America are very similar to each other but different from the coffee strains from Africa. And the opposite is true as well. African coffee strains are all pretty similar to each other but different from the South American strains. The same sort of thing is true for cacao strains as well.
You can think of coffee and cacao strains as the large, flightless birds of the yeast universe. Like a rhea, emu, or ostrich, they stay on their own continent. Wine yeasts are more like those chickens that are basically the same worldwide because humans have taken them along with them in their migrations.
The first step in their analysis was for Ludlow and coworkers was to get a hold of a bunch of different samples of cacao and coffee yeast strains from all over the world. They managed to get 78 cacao strains from 13 different countries and 67 coffee strains from 14 countries. The countries were from Central and South America, Africa, Indonesia and the Middle East.
The next step was to compare the genomes of these strains with each other and with the wine strains. They decided to use a technique called restriction site-associated DNA sequencing, or RAD-seq, that would give them an in depth look at around 3% of the yeast genome. As there was already a database with 35 wine strains that used the same method, Ludlow and coworkers only needed to generate data for their newly isolated strains.
These data revealed that coffee and cacao yeast strains were very different from one another. It also showed that the closer two coffee or cacao strains were to each other geographically, the closer they were together genetically. Using just these strains they could accurately predict the country of origin for a coffee yeast strain 79% of the time and 86% of the time for those associated with cacao.
The researchers next expanded the number of species they compared by using two additional databases. One included RAD-seq data from 262 strains from a wide variety of different places while the other contained another 57 strains.
This analysis generated 12 distinct groups of yeast, many of which had been identified before. Their new strains formed four new groups which they called South America Cacao, Africa Cacao, South America Coffee and Africa Coffee.
By comparing the four groups to the eight older ones, they were able to see that the new groups were not novel but instead were made up of mixtures of some of the other known groups. And who they shared alleles with depended on where the yeast strain was located. So, for example, the two South America groups shared alleles with the North American Oak group while the two African groups shared alleles with the Asian and European groups.
It looks like that, unlike with wine where there are a limited set of best yeast strains that most people use, the yeast strains involved with making chocolate and coffee are continent and even country specific. This suggests that people either took their wine yeast with them when they moved or that cross contamination throughout the world resulted in homogenization of wine yeasts. Sort of like the chickens Pacific Islanders brought with them whenever they settled on a new island.
It is a very different story for cacao and coffee yeast strains. While there was cross contamination within countries and even continents, there was no worldwide contamination. The rhea stayed in South America and the ostrich in Africa.
Wherever these strains come from, they work hard to make our chocolate, coffee, bread, wine, and beer. What an amazing bounty! Make some room, Dog, good ol’ Saccharomyces cerevisiae is joining you as man’s best friend.
by Barry Starr, Ph.D., Director of Outreach Activities, Stanford Genetics
April 6, 2016
In the book Dune, the mentat Thufir Hawat is captured by the evil Harkonnens and given a residual poison. He can only stay alive by getting a constant dose of the antidote. Once it is withdrawn, he will die.
A new study in the journal GENETICS by Dodgson and coworkers shows that the same sort of thing can happen to yeast that carry an extra chromosome. In this case, certain genes on the extra chromosome turn out to be like the residual poison. And a second gene turns out to be the antidote.
Once that second gene is deleted, the yeast cell dies. It has been deprived of its antidote.
This synthetic lethal phenotype isn’t just a cool finding in yeast either. Cancer cells invariably have extra and missing chromosomes. If scientists could find similar “antidote genes” in specific types of cancers and target them, then the cancer cell would die. And this would happen without damaging the other cells of the body that have a typical number of chromosomes.
The first thing these researchers did was to make separate yeast strains each with an extra chromosome I, V, VIII, IX, XI, XII, or XVI. The next step was to see what happens when every gene was deleted individually, one at a time, from each strain.
As expected, these yeast did pretty well when a gene on the extra chromosome was deleted. So, for example, a strain with an extra chromosome I tolerated a gene deleted from chromosome I. This makes sense as this just brings that gene back to its normal copy number.
But this was not the case with chromosomes VIII and XI. Here deleting genes on the extra chromosome often had a negative effect. This suggested that the screen probably had a high number of false positives and these researchers later confirmed this.
Likely reasons for the high number of false positives include the strain with the extra chromosome being W303 and the deletion strain being S288C, errors in the deletion collection itself, and what they refer to as neighboring gene effects. Basically this last one is the effect that deleting a gene has on nearby genes.
Once Dodgson and coworkers corrected for these problems, they found two broad sets of phenotypes – general and chromosome specific.
The general ones were the ones shared by most or all of the strains. These were deletions that affected the yeast no matter which chromosome they had an extra copy of.
For the most part, these genes were enriched for the Gene Ontology (GO) term vesicle-mediated transport, indicating that they have something to do with the transportation of substances in membrane-bounded vesicles. For example, deletion of MNN10, HOC1, and MNN11, genes all involved in protein transport and membrane-related processes, had a negative effect on many of the yeast strains with an extra chromosome. Consistent with this, brefeldin A, a drug that targets protein trafficking, negatively affected most of the strains.
Another gene that affected many of these strains when deleted was TPS1. This gene encodes a subunit of trehalose-6-phosphate synthase, a key enzyme for making trehalose, a molecule that helps yeast deal with stress. Perhaps not surprisingly, having an extra chromosome is stressful!
In addition to the genes that affect many strains with an extra chromosome, there were also genes that were chromosome specific. The best characterized of these was the EDE1 gene in the strain with an extra chromosome IX. Deleting EDE1 in this strain increased its doubling time by more than 80 minutes while only causing an increase of 5 minutes in the doubling time of wild type yeast. This was a severe phenotype in their assay.
They next tried to find which gene on chromosome IX might be responsible for the severe effect of deleting EDE1. Since EDE1 is known to be involved in endocytosis, they looked for genes involved in the same process. And they found one – PRK1.
The strain with a deleted EDE1 gene and an extra chromosome IX was rescued by deleting one copy of the PRK1 gene. The extra PRK1 gene was the poison and the EDE1 gene was the antidote.
If a similar pair could be found in cancers that often have the same set of extra chromosomes, then perhaps scientists could develop drugs that target an antidote gene. Now the cancer cells would die and the “normal” cells would be fine. Thanks again, yeast, for pointing us toward new ways to treat human disease.
by Barry Starr, Ph.D., Director of Outreach Activities, Stanford Genetics
March 30, 2016
For almost 50 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 Nobel laureates and many of today’s leading scientists.
The application deadline is April 15th, so don’t miss your chance! Find all the details and application form here.
This year’s instructors – Grant Brown, Maitreya Dunham, and Marc Gartenberg – have designed a course (July 26 – August 15) that provides a comprehensive education in all things yeast, from classical genetics through up-to-the-minute genomics. Students will perform and interpret experiments, learning about things like:
- How to Find and Analyze Yeast Information Using SGD
- Isolation and Characterization of Mutants
- Transformation of Plasmids & Integrating DNAs
- Meiosis & Tetrad Dissection as well as mitotic recombination
- Synthetic Genetic Array Analysis
- Next-Gen. whole-genome and multiplexed DNA barcode sequencing
- Genome-based methods of analysis
- Visualization of yeast using light and fluorescence microscopy
- Exploring synthetic biology with CRISPR/CAS9-directed engineering of biosynthetic pathways
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. Significant stipends (in the 30-50% range of total fees) are available to individuals expressing a need for financial support and who are selected into the course.
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). There’s also a sailboat trip, a microscopy contest, and a mysterious “Dr. Evil” lab!
Last year’s Yeast Genetics & Genomics Course was loads of fun – don’t miss out!