Author: Noah Steinfeld
Editors: Alex Taylor, Christina Vallianatos, and Bryan Moyers
In 2001 the Nobel Prize in Physiology or Medicine was awarded to three scientists, Leland Hartwell, Tim Hunt and Paul Nurse, for their discoveries of key regulators of the cell cycle. Normally, before a cell can divide, it must undergo several phases of the cell cycle in a precise order. First, a cell grows in size, then duplicates its DNA, and finally distributes its DNA evenly between two daughter cells. The three researchers played seminal roles in identifying the mechanisms by which cells transition from one cell cycle phase to the next.
These fundamental discoveries are not only crucial to our understanding of biology, but have applications in human disease. Many types of cancer are linked to mutations that cause cells to move quickly through or even skip some parts of the cell cycle, making cell cycle regulation a hot area of biological research. Given the implications this research has for human health, it might surprise you that many cell cycle regulators were not first discovered in humans. Instead, these cell cycle regulators were identified and characterized in model organisms including yeast and sea urchins.
“But what do I have in common with the yeast I use to bake bread?” you might ask. As it turns out, a lot more than you’d think.
What Can We Learn about Humans from Model Organism Research?
Research performed in model organisms relies on the guiding principle that what we learn about them will provide insight into other organisms. This principle is based on the idea that genes essential for survival will change little during evolution since mutations that affect the function of essential genes can result in death. So if genes in two different species are very similar in DNA sequence, researchers can assume that these genes perform similar and important roles in the cell and in the organism. This assumption allows the researchers to study a gene in a model organism (e.g. yeast) and learn about a similar gene in humans.
Throughout history, scientists have found that this assumption holds true in many situations. For example, Paul Nurse identified CDC2, a key cell cycle regulating gene, in yeast. Later, Nurse identified a gene in humans with nearly identical function: CDK1. These two proteins encoded by these genes are identical at 63% of positions in the protein sequence, a remarkable number considering humans and yeast have been evolving separately for almost a billion years.
This is not an isolated example. Researchers at the University of Texas at Austin examined how often genes in distantly related species retain same functions. They removed over 400 essential genes from yeast, one at a time, and replaced each one with its human equivalent. For 47% of essential genes tested, yeast cells survived when the gene was replaced with its human equivalent, suggesting that these genes have maintained the same functions over about a billion years of evolution. This result supports the idea that what we learn in model systems can apply to other organisms, including humans.
Perks of Using Model Organisms
By using model organisms, scientists can answer fundamental questions in biology. Model organism research has not only given us insight into how cells control their division, but has helped bring us countless advances in biology and medicine. Ninety-four out of 106 Nobel Prizes in physiology or medicine were awarded for discoveries that relied on animal research, including every prize for the past 30 years. Research performed in yeast alone accounts for five Nobel Prizes since 2001.
Each model organism has unique advantages that make it ideal for certain types of studies. For example, yeast is frequently used as a model system because its genes can be easily and quickly edited, including removing an entire gene or introducing a specific mutation into a gene. This type of precise gene editing was extremely difficult or even impossible in more advanced model systems until the recent advent of more sophisticated genetic technologies.
Other model organisms are used to study more complicated processes. Single-celled organisms like yeast cannot be used to understand the steps that humans and other organisms go through when developing from a single cell to an embryo then to an adult. Scientists can then use more complicated model organisms, such as fruit flies and worms, to understand these developmental processes. For example, worms can be used to understand how an external signal, such as pain, is turned into a response from the organism via neurons. This process is much easier study in a worm than a human. Humans have approximately 86 billion neurons in the brain alone while a worm has only 302 neurons in its entire body.
Threats to the Funding of Model Organism Research
Despite the importance of research in model organisms, the National Human Genome Research Institute (NHGRI) recently announced a 30-40% funding cut for several of the Model Organism Databases (MODs), specifically the yeast, worm, fly, zebrafish, and mouse databases. MODs are community resources that collect and curate experimental results from peer-reviewed literature such as DNA sequences of genes, protein expression data, and protein functions. These are crucial resources for any researcher who works with one of listed model systems.
These budget cuts have sparked outrage from many leaders in the model organism research community, who have urged the NIH director, Dr. Francis Collins, to continue adequate and sustained funding to the individual MODs. With a new presidential administration, future funding for biomedical science is uncertain. The funding cut has the potential to handicap scientists who are taking advantage of one of the cleverest methods in biology.
To maintain funding for the NIH and the many resources it provides, including the model organism databases, you can contact your congressperson and urge them to support NIH funding in the federal budget.
About the author
Noah Steinfeld is a third-year student in the Cellular and Molecular Biology PhD program at the University of Michigan. Under the guidance of Dr. Lois Weisman, Noah is studying how, when cells divide, they make sure that organelles, cellular subunits with important specialized functions, are evenly distributed in both daughter cells. Before coming to Michigan, Noah graduated from Yale University with a degree in Molecular Biophysics and Biochemistry and before that, he spent his youth in snowy Buffalo, New York. In his spare time, Noah watches TV (Superhero shows and the bachelor franchise are two favorites), plays Frisbee, and supports UMich sports teams. Follow him on Twitter and connect with him on Linkedin!
Read all posts by Noah here.