Using yeast in biology

Baker’s or budding yeast (Saccharomyces cerevisiae) has long been a popular model organism for basic biological research. In the lab it is easy to manipulate, can cope with a wide range of environmental conditions and controls cell division in a similar way to our cells. In 1996, it was the first eukaryotic organism to have its genome sequenced.

Yeast was the first eukaryotic organism to have its genome sequenced.

However, since Baker’s yeast was discovered, other yeasts have been found to have equally useful properties.

Yeast chromosomes share a number of important features with human chromosomes.

Fission yeast (Schizosaccharomyces pombe) has become a popular system for studying cell growth and division. It is useful partly because it is easy and inexpensive to grow in the lab, but also because its cells have a regular size and grow only in length, making it very simple to record cell growth. Fission yeast chromosomes share a number of important features with human chromosomes making the organism a very useful model in human genetics. The S. pombe genome sequence was published in 2002.

How are humans and yeast similar?

An important feature of these yeasts that makes them such useful organisms for studying biological processes in humans, is that their cells, like ours, have a nucleus containing DNA packaged into chromosomes.

Most metabolic and cellular pathways thought to occur in humans, can be studied in yeast. For example, studying signalling proteins in yeast has advanced our understanding of brain and nervous system development.

Yeast cells divide in a similar manner to our own cells. In fact, it has been found that many of the genes that work to regulate cell division in yeast, have equivalents that control cell division in higher organisms, including humans.

The S. cerevisiae and S. pombe yeast genomes have just over 12 million base pairs.

Both the S. cerevisiae and S. pombe yeast genomes have just over 12 million base pairs. S. cerevisiae has around 6,000 genes while S. pombe has just over 5,000. At least 20 per cent of human genes known to have a role in disease have functional equivalents in yeast. This has demonstrated that many human diseases result from the disruption of very basic cellular processes, such as DNA repair, cell division, the control of gene expression and the interaction between genes and the environment.

It also means that yeast can be used to investigate human genetics, and to test new drugs. Thousands of drugs can be tested on yeast cells containing the functional equivalent of mutated human genes to see if the drugs can restore normal function. These compounds, or molecules like them, might then be possible treatments in humans. Although, it is important to say that this is not the case for all drugs so there is a strong rationale to use other model organisms as well as yeast in drug development.

Yeast studies

Between 2001 and 2013, four Nobel Prizes were awarded for discoveries involving yeast research.

Yeast is a powerful model organism that has enabled a better understanding of human biology and disease. Between 2001 and 2013, four Nobel Prizes were awarded for discoveries involving yeast research, an impressive number for a single organism.

The genome of S. cerevisiae yeast was published in 1996 and the S. pombe sequence in 2002. As a result, projects have been initiated to determine the functions of all the genes in these genomes. One such project, the Saccharomyces Genome Deletion Project, aimed to produce mutant strains of yeast in which each one of the 6,000 genes in yeast is mutated. From this it was hoped that the precise function of each gene could be identified.

Other projects are looking at highlighting the different protein interactions that occur in yeast cells to identify potential targets for new drugs.

Yeast, the cell cycle and cancer

Over the last few decades, scientists have been working hard to identify all of the mutations that cause cancer in humans. Many of the mutations found so far are in genes involved, in some way, with cell division and DNA replication. In many cases these mutations have been found in other species, like yeast, before their relevance in human cancer was realised.

In 2001, Leland Hartwell, Paul Nurse and Tim Hunt shared the Nobel Prize for establishing the role of different genes in controlling cell division.

In 2001, three scientists shared the Nobel Prize for their independent work establishing the role of different genes in controlling the cell cycle and investigating the link between the cell cycle in yeast and that in humans. These three scientists were Leland Hartwell, Paul Nurse and Tim Hunt.

Leland Hartwell, a biologist, was one of the first scientists to discover some of the mutations involved in cancer. He decided he wanted a simple, single-celled, easily manipulated organism as a model system for studying cancer and the control of cell division. S. cerevisiae yeast fitted the criteria perfectly. Through his work he found that the genes involved in the ‘cell division cycle’ (CDC) in S. cerevisiae yeast, were also found, in more or less the same capacity, in humans. Over his career, Leland went on to identify more than 100 genes involved in the control of cell division. He found that in cancer cells, mutated genes that normally stimulate cell division start acting like accelerators stuck ‘on’ in a car. Meanwhile, he found that mutated genes normally responsible for suppressing cell division stop working, much like malfunctioning brakes.

Paul Nurse followed Leland’s example but this time using S. pombe yeast to explore the control of cell division. In the middle of the 1970s he discovered a gene in S. pombe yeast called cdc2 and found that it had a key role in controlling cell division. In 1987 he then found the equivalent gene in humans which was later given the name Cdk1. This then led to the discovery of other CDK molecules involved in controlling cell division in humans.

During the early 1980s, while studying sea urchins, Tim Hunt discovered cyclin, a protein formed and then broken down during each cell division. It was found that cyclins bind to the CDK molecules, discovered by Paul Nurse, and switch them on during the control of cell division. He also showed that these cyclins are degraded at each cell division, a mechanism proved to be of huge importance for controlling the process.

The discoveries of Leland Hartwell, Paul Nurse, Tim Hunt and others using yeast as a model organism, have contributed significantly to the generation of a universal view of how cell division is controlled in eukaryotic cells. This understanding has had broad applications within a number of different fields in biology, including the prevention, diagnosis and treatment of cancer.

Yeast and Parkinson’s disease

Research using S. cerevisiae as a model organism has given hope to people with Parkinson’s disease. Parkinson’s disease and other neurodegenerative diseases such as Alzheimer’s and Huntington’s are characterised by protein misfolding, resulting in the build-up of toxic cells in the central nervous system.

The protein α-synuclein aggregates to form Lewy bodies, the hallmark of conditions such as Parkinson’s disease and dementia.

Cellular build-up of the protein, α-synuclein, is known to greatly increase a person’s risk of developing Parkinson’s disease and is also found to affect yeast.

Elevated or mutated forms of α-synuclein wreak havoc on our brain cells. This protein aggregates to form Lewy bodies, the hallmark of conditions such as Parkinson’s disease and dementia and consequently cause major disruption to numerous neurological processes. Similarly, when engineered to produce high levels of α-synuclein, cells show signs of signs of damage and their growth becomes slower.

S. cerevisiae cells can be used as living test tubes.

Knowing this, scientists have been able to use S. cerevisiae as an effective tool to characterise factors and mechanisms that regulate α-synuclein toxicity. S. cerevisiae cells can be used as living test tubes to test the function of compounds that could be used to reverse the effects of α-synuclein on brain cells and therefore treat Parkinson’s.

By using a living organism such as yeast, researchers are able to see the impact of a drug on an entire organism that has been genetically modified to mimic the biochemical mechanism of a disease found in humans.