In November 2012 I had my PhD viva – a defence to other academics of the work I had carried out over the previous four years. The primary goal of the viva is to establish that the student has made a valuable and original contribution to his chosen field of research. Fortunately my thesis was considered sufficiently valuable and original that I passed.
Below is a defence to a different, wider, audience – the Irish public, who were responsible for funding me during the course of my PhD. Given the ongoing public discourse on the value of basic science in Ireland, I felt this was worth writing up.
Everyone Loves Genetics
When I tell people I meet that I work in genetics, they usually respond very enthusiastically. They may bring up some genetics story they have read in the news – such as the high prevalence of cystic-fibrosis in Ireland, the Angelina Jolie BRCA story, or the fact that many of us are apparently part-neanderthal. It really is a pleasure to work in a field that the general public has a real interest in. That said, when I mention that I study yeast genetics, the reaction changes somewhat. It seems like such an arbitrary and obscure research topic, the sort that could only survive in academia. Given that for my PhD I was funded by the Irish taxpayer, it also seems to many like money that could be better spent elsewhere. Why study a fungus when there’s cancer to be cured? I’ll try and address this here – outlining some of the reasons why geneticists study yeast, and also why I believe my specific research area is of value.
Yeast are like us!
Perhaps the most important thing to know about yeast is that, like us, they are Eukaryotes. This means it has a nucleus, a little compartment inside every yeast cell that houses its DNA. In fact yeast are remarkably similar to us in a lot of ways. Yeast cells have to carry out many of the same tasks that human cells do – they have to replicate DNA, they have to turn DNA into proteins, and they have to direct molecules around inside their cells. Many yeast genes have counterparts (orthologs) in humans, and these counterparts often carry out the same function in both species. So discovering what functionality a yeast gene is responsible for often gives insight into the functionality of the human counterpart. This observation has resulted in a number of Nobel Prizes in Medicine for yeast geneticists.
Yeast and Nobel Prizes in Medicine
For instance – Paul Nurse and Lee Hartwell discovered a number of genes that control cell division in yeast. Cell division is a vital part of life – it’s how we go from sperm and egg to full human being – and is also a process that is dysregulated in cancer. The genes that Nurse and Hartwell discovered in yeast have counterparts in humans that appear to function in the same way.
Similarly, Randy Schekman shared a Nobel Prize in 2013 for his work identifying genes responsible for vesicle trafficking in yeast. Inside all Eukaryotic cells there are a number of different compartments, such as the aforementioned nucleus. This compartmentalisation has lots of advantages, including ensuring that harmful molecules are not free to bounce around the cell. However, it creates a need for a trafficking system to allow different molecules to be moved from compartment to compartment when required by the cell. Schekman focussed on understanding this system in yeast, identifying a number of genes involved in the trafficking process. Another scientist, James Rothman, later studied the same system in mammalian cells and found that many of the yeast genes identified by Schekman had functionally similar human counterparts. Finally, the third scientist to share the 2013 prize, Thomas Südhof, worked on mammalian nerve cells to identify how the trafficking machinery identified by Schekman and Rothman ensured that molecules were delivered to the right place at just the right time, a critical part of how nerve cells communicate in the brain.
So yeast can provide insight into topics important for human health ranging from cell division and cancer, to signalling in the brain.
Yeast is easy!
Thus one reason to study yeast is to get a better understanding of specific genes and processes – which genes are responsible for specific tasks (e.g. controlling the cell cycle, controlling trafficking) and what a specific gene of interest does.
But that doesn’t really answer the question of why we should study yeast in particular, instead of other organisms. Why not study humans and our cells directly? The short answer is because it’s much much easier to study yeast! It’s very easy to grow in the lab and it’s very easy to manipulate genetically. The latter is especially important for genetics – it’s far easier to manipulate a specific yeast gene and see what happens, than it is to manipulate its human counterpart. Also important is yeast’s relative simplicity – the most widely studied yeast has ~6,000 genes vs ~20,000 in humans and as it is a single-celled organism it does not have the added complexity of multiple cell types like us (kidney, liver etc). For these reasons yeast is something of a proving ground for new technologies – typically new molecular biology and genetic approaches are applied to yeast long before they are applied to humans (e.g. we had a yeast genome before a human genome).
Yeast as a model system
The ease of growth and genetic manipulation, combined with its relative simplicity, make yeast an excellent tool for understanding general features of biological systems. Compared to identifying the functions of specific genes this is a more abstract but equally important goal.
To explain what I mean by understanding general features of biological systems it’s probably easiest to give an example. Cells, of all varieties, need to respond to stimuli. This response typically involves increasing the production of specific proteins, often hundreds at a time, in a coordinated fashion. The process by which this happens involves complex ‘regulatory’ networks, which regulate the production of proteins at specific times and under specific conditions. In humans, because we have multiple different cell types and many more genes than yeast, these networks are significantly more complex than in yeast. By studying and mapping these networks in yeast, we can hope to learn principles that may be broadly used in all species, e.g. what patterns are used to ensure that hundreds of genes are ‘turned on’ at just the right time?
Yeast are awesome!
I have highlighted two reasons to study yeast : 1) it provides insight into specific genes and processes and 2) it allows us to explore general features of biological systems. There are many more reasons – it helps us make beer and bread – but even if all we are interested in is the relatively narrow field of human health, yeast can provide us an enormous amount of knowledge that we could either not get any other way, or would take us far longer to get using other systems.
In my next post I’ll discuss the merits of studying genetic interactions, my particular area of research.