Yeast is one of most thoroughly researched model organisms in modern cell biology – as evidenced by the 11 Nobel Laureates awarded for their breakthrough discoveries in yeast towards cell function and cancer since 2001.
Most recently, the 2016 Nobel Laureate, Dr. Yoshinori Ohsumi, was awarded for his groundbreaking work on autophagy in yeast. This is the process where cells recycle their worn out parts, a function implicated in many diseases including cancer, Parkinson’s, and Alzheimer’s. For example, a specialized form of autophagy that targets damaged mitochondira (mitophagy) may not be working well in people with Parkinson’s disease.
Like many of the Nobel Laureates before him, Ohsumi’s work uncovered basic biological properties using a model organism. Ohsumi had worked with yeast previously as a tractable experimental system – a simple single celled organism separated from humans by hundreds of millions of years of evolution but still sharing many of the same essential biological processes. In his prior work, he had identified many proteins in a subcellular component of yeast cells known as the vacuole – which was critical as there was evidence that the vacuole performed the same role in yeast cells as the lysosome in mammalian cells. The key for him was to find a way to disrupt this process in yeast so that he could identify the genes underlying autohphagy.
Ohsumi verified the existence of this function by creating yeast mutants that had vacuoles but could not digest anything – the idea was that there would be a build-up of autophagosomes (specially packaged cellular material sent off for recycling) in the vacuole because his yeast mutants lacked the proper recycling enzymes. As a result he saw that these yeast mutants developed enormous vacuoles bloated with autohpagosomes – he had the makings of a yeast screen! Armed with a motivated grad student, a microscope, and dogged molecular biology, Ohsumi interrogated over 38,000 gene mutants over the course of 2 years to identify the initial 15 genes essential for autophagy (subsequent studies by Ohsumi and his students, and others, uncovered even more genes implicated by autophagy as well as other essential pathways ).
Ohsumi’s story and breakthrough approach is not one just common to Nobel Laureates, but to all researchers interrogating their cell system models. The first biological breakthrough is forming or panning for screening criteria (bloated vacuoles in Ohsumi’s case, or temperature-sensitive mutants in 2001 Nobel Laureate Dr. Lee Hartwell’s case). With a key like that in hand, the power of yeast genetics combined with FenoLogica’s simplified imaging capture and analysis pipeline can help researchers quickly hone in on the actionable genomics. For Ohsumi this was completed by exposing yeast to a genetic screen (which randomly introduced mutations) then inducing autophagy and manually identifying/ analyzing the implicated mutants. Ohsumi completed this groundbreaking work in the early 1990’s. The tools and screening approach he used are still state-of-the-art today. Imagine reducing the time spent capturing and analyzing this type of data by 50-fold.
FenoLogica’s technology does just that! Learn more.