Skip to 0 minutes and 9 secondsHi and welcome. My name is Michael Chang. In this lecture series, me and my colleague Liesbeth Veenhoff will discuss how the budding yeast, Saccharomyces cerevisiae, can be used to study ageing in humans. Liesbeth and I are both PIs at ERIBA, using yeast as a model organism for our respective research. There are many species of yeast that are actively used as model organisms in research. The two main ones are the budding yeast, Saccharomyces cerevisiae, and the fission yeast Schizosaccharamyces pombe. These two yeast species are actually very evolutionary distant, having last shared a common ancestor about 300 to 600 million years ago. So it is often very informative to study a biological process in both species.

Skip to 0 minutes and 55 secondsAs their names suggest, budding yeast cells divide through a budding process where a new daughter cell develops by budding off of a mother cell, whereas fission yeast divide by medial fission to produce two daughter cells of equal size. For the purpose of this lecture series, when we say yeast we are talking about budding yeast. Budding yeast has been used since ancient times for brewing, winemaking, and baking. And if you're from the UK, Australia, or New Zealand, you're probably also familiar with Marmite or Vegemite, which are products made from yeast extracts.

Skip to 1 minute and 29 secondsJust to put yeast into evolutionary perspective, here's a phylogenetic tree of life which I took from Wikipedia, showing the relationship between species whose genomes had been sequenced as of 2006. Not surprisingly, most of the species were bacteria. Zooming in on the eukaryotic species, I've highlighted where we Homo sapiens are in relation to S. cerevisiae. Yeast and humans last shared a common ancestor over a billion years ago. That we can learn so much about ourselves from studying such a distantly related unicellular organism, I think is quite remarkable. It really highlights how interconnected all life on Earth is. Although we are mostly interested in human biology, it is usually not possible to perform experiments on humans.

Skip to 2 minutes and 20 secondsSo that's why researchers study model organisms. But why yeast? Well, in addition to its long history of being used by humans to bake bread and brew beer, it has many attributes that make it a great model organism. For example, it grows really fast. You can grow them either as haploids or diploids. It's easy to mate haploids to generate diploids, and you can induce the sporulation of diploids to get haploids. This makes doing genetics very easy. You can efficiently put exogenous DNA into yeast cells, either maintained as autonomously replicating plasmids, or integrated into the genome. Yeast is very good in doing homologous recombination. This means that you can integrate DNA at specific locations in the genome.

Skip to 3 minutes and 10 secondsIt's also a fantastic system to perform genetic screens. And these are just some of the advantages of using yeast. Budding yeast was the first eukaryotic organism to have its genome sequenced back in 1996. Its genome is about 12 megabases in size with a total of about 6,000 genes. In comparison, the human genome is three gigabases in size with about 20,000 genes. Many genes important for human biology were discovered by studying their homologues in yeast. Nearly 1,000 yeast genes are members of orthologues gene families associated with human disease. For most of these genes, their mammalian homologue is functional in yeast and can complement the yeast deletion mutant. So I hope I've convinced you that yeast is a great model organism.

Skip to 4 minutes and 3 secondsBut still, how can yeast, a unicellular organism, be used to study ageing of a complex multicellular organisms such as humans? I've listed three ways here. First, individual yeast cells can undergo only a finite number of mitotic divisions before they die. We refer to this as replicative ageing. And this is analogous to the ageing of proliferating human cell types, such as stem cells. Second, yeast cells lose viability the longer they stay in a post-mitotic stationary phase. This has been compared to the ageing post-mitotic cells of the human body, for example the neurons in the central nervous system.

Skip to 4 minutes and 48 secondsLastly, most human somatic cells do not express sufficient telomerase to prevent telomere attrition, and this has been proposed as one reason why we age. We can study this in yeast by knocking out telomerase and seeing what happens. Our lecture series will focus on the first and third models of ageing. Liesbeth will take you through what we currently know about replicative ageing in yeast. And I will discuss how yeast has been used to study telomere-attrition-induced ageing.

Baker's yeast as a model organism

Most of you are probably familiar with baker’s yeast from its applications in home-cooking, industrial food processing, brewing, and fermentation. But did you know that this micro-organism is also an excellent model in various branches of biological research, including the study of human ageing?

How could a mundane singe-cell organism like yeast reflect the biology of such an advanced species as us, humans? In his lecture Michael Chang will show you that both species possess a very similar cell nucleus, making them both eukaryotes that share a common ancestor early in evolution.

This evolutionary relatedness also explains that yeast cells and human cells show similar ageing processes as we see in dividing and resting cells. Michael will introduce you to these different ageing processes like replicative ageing, chronological ageing, telomere-attrition-induced ageing, and how these are studied in yeast.

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Why do we Age? The Molecular Mechanisms of Ageing

University of Groningen

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