Yeast produces not only bread and wine

[The Leaven – exploring the relationship between science and religion (cont)]

The last post established why yeast is used as a model organism to study molecular biology but how and what is it used for? The last century saw a molecular enlightenment, yeast was cemented as a key component of that movement. In the 1950’s, molecular biologists constructed a  Saccharomyces cerevisiae strain containing biochemical markers (antibiotic  resistance or amino acid selection) known as S288C from the fig strain mentioned in the previous post, EM93. It was soon discovered that self-replicating elements of DNA found in bacteria called plasmids could also be made to function in yeast. Yeast cells multiply rapidly and the overall effect of a mutation in a certain gene can be measured biochemically or by observation under the microscope. If DNA fused to reporter genes is inserted into the self replicating DNA from bacteria and then introduced into the yeast cell, it can be propagated and then extracted. This technique is called cloning as it replicates an identical copy of a gene, has been used to mass-produce proteins and vaccines. In yeast, cloning was used as early as 1980 to produce Hepatitis B vaccine. Since then it has produced a multitude of proteins and vaccines including: insulin, growth hormone, haemoglobin, oestrogen receptor and interferons.

Cloning can also take place in bacteria such as Escherichia coli, these cells divide faster than mammalian cells but are a lot smaller so there is a limit in the size of the protein that can be cloned. As a consequence of this other cells types are now also used for cloning such as those derived from mammals, insects and viruses. Cloning provides an extremely economical way to reproduce human proteins. They replace the need for animal production and reduce the risk of transferring unwanted diseases, such as, CJD from growth factor. Although great advances have been made, the systems are still not perfect and have their limitations according to the type of protein that can be cloned, as some are toxic to the cell, and introduction of unwanted mutations occurs far more frequently when selection is not acting on the protein. Most organisms, including bacteria, have their own DNA repair systems that detect mutations. Foreign DNA has a higher chance of retaining mutations in a host cell as it is not detected through normal cell function, a problem to biotechnology that is successfully addressed in natural systems by selection. The use of these systems with limitations causes uncertainty and increases risk factors, subjects which are discussed  in future posts. It seems yeast occasionally retains its Biblical ability to behave in a corrupt way.

Protein interactions: Ribonuclease-inhibitor protein grabbing and surrounding the ribonuclease A enzyme. Image by Dcrjsr.

Following the heady days of protein engineering, yeast laboratories, through intra-science communication, successfully completed the enormous challenge to complete the first fully sequenced eukaryotic genome. This was achieved using strain S288C and relatively archaic apparatus compared to the robotic systems used to decode the human genome. Eventually, over 6,000 genes were unravelled from the yeast nucleus. The yeast genome is 200 times smaller than the human genome but almost four times larger than that of E. coli. This achievement marked a milestone in biological history. Yeast biologists did not stop at just sequencing the genome. In a striking example of inter-organisation collaboration, nominated laboratories began deleting single genes from individual yeast cells through advances in polymerase chain reaction (PCR), a technique that can amplify a single gene from the cells DNA. A marker/reporter gene flanked by target DNA is amplified by PCR technique and then inserted into the yeast cell. Non-homologous recombination replaces the genomic gene with the introduced marker/reporter gene. Biochemical tests were then carried out on the mutant yeast strains to uncover the functional analysis of hundreds of different gene products. This work elucidated many gene functions and undoubtedly contributed to the discovery of many analogous human genes. This information has been collated into several databases to provide a plethora of data available for bioinformatics across the internet. Genes placed on microarray slides and subjected to various environmental conditions and variations of DNA recombination techniques have increased the quantity of this information, enabling researchers to compose complicated hypotheses and uncover new cell processes without even entering a laboratory.

Many would expect yeast’s contribution to scientific research to stop at this point. Exhausted by constant, investigative probing. In contrast, the yeast story continues. It has also been used as a vehicle to investigate protein interactions first with native yeast proteins and then later with proteins from any other organism. Genes can be fused to protein tags, introduced into yeast cells and reporter genes within the cell can detect if the proteins produced from the introduced DNA interact. This procedure is known as the yeast 2-hybrid technique. Several variations to this technique exist, again modifying it to be used in other in cell cultures from other organisms. These techniques, in a rudimentary way, can also be used to evaluate post-translational modifications in proteins, to see how gene products are modified by the cell. Compared to the amount of gene sequencing data available the amount of protein interaction data is still fairly incomplete with the function of many gene products still unknown.

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The molecular, vegetative animalcule

[The Leaven –  exploring the relationship between science and religion (cont)]

Yeast is a domesticated organism that has become almost indispensable in modern society. Although unessential to the staple diet, supermarket shelves are crammed with products that require yeast fermentation. Bread, chocolate and alcohol production all involve the metabolic activity of these simple single-celled microbes. Restaurants, bars, clubs and many aspects of social behaviour revolve around yeast products.

Throughout the centuries yeast has been the focus of domestic and industrial life. While it’s fermenting ability has  been the focus of many different hypotheses and paradigm shifts. Fermentation was once thought to be the consequence of a chemical reaction by some kind of substance and not the metabolic activity of a living organism. During the Biblical era there would have been no conception that the metabolic pathway of a microscopic bug was the source of fermentation.

Yeasts are naturally abundant in the environment especially in the soil where they are transferred, by insects or other means, on to the skins of fruit and animals, including humans. The environment contains many different types of yeast, from those that cause fungal infection (Candida spp.) to others that are used in the baking industry and in wine-production (Saccharomyces spp.). Yeast belongs to the kingdom Fungi and the division Ascomycota. In recent times it has become a major player in biological research and is now one of the most studied organisms on Earth. It was the first eukaryotic organism to have a fully sequenced genome. The majority of its genes have been researched and functionally analysed and, as many of these have analogues in other multicellular organisms, it is therefore possible to study molecular processes from mammalian systems within a unicellular model eukaryote. It is also well established as a favourable alternative to animal model systems.

Large-scale experiments involving computers, robotics and new molecular techniques, such as polymerase chain reaction (PCR) to amplify genes and DNA micro-arrays, that arrange hundreds of these genes onto a small grid, have generated such a large amount of data that new scientific disciplines, eg., genomics, transcriptomics,  have evolved in order to process it all into meaningful results. The simplicity of the yeast life-cycle has made it invaluable to medical and biotechnological research. Certainly, yeast has had a great impact on 21st century society that has inflicted on social behaviour and medical research. Anthropology would have evolved differently if this organism ceased to exist.