Unlocking key answers about cell function to improve cancer treatment

Researchers at the Peter Mac Institute have found an answer to a decades-old question about cell function that could lead to improved cancer treatments in the future.

Every cell in the human body has the same DNA, but different cells perform different functions. This study, published in the journal Nature Genetics, helps explain how this is possible, and the implications could be huge. Professor Mark Dawson, physician-scientist and deputy director of research at Peter Mac, said he was excited about new discoveries that better explain how a cell's fate is determined.

"Cell function is the result of 'transcription factors' that scan our DNA and determine which genes should be turned on and to what extent," he said.

"We have studied how these transcription factors recruit and deliver the machinery needed to turn on genes. Until now, we did not know how 'transcription factors' select the correct machinery to read and express a gene.

"This has been a question for many years, and we are glad to have helped solve part of the problem, because this knowledge of how exactly transcription factors make decisions about which mechanism to activate a gene provides us with fundamental knowledge about life."

Comparative CRISPR screens identify cofactors required for nine different transcriptional activators (ADs). Source: Nature Genetics (2024). DOI: 10.1038/s41588-024-01749-z

Research has shown that transcription factors select a unique set of components to control gene expression, creating a desired action, whether it is controlling a cell's energy consumption, triggering an immune response, or another function needed by our body. Professor Dawson said it could be compared to how cars are built and explained how this important discovery is key to finding better treatments for various diseases.

"An F1 racing car is very different from a family minivan or even a tractor; some cars are designed to go fast, others to carry valuable cargo, and some to do hard work," he said.

"We found that the same is true for gene expression, and this is determined by the components recruited by transcription factors. These can determine which genes can change quickly, for example when we need to fight an infection and need a quick response, or which genes must work slowly and steadily to produce the messages necessary for cellular housekeeping function.

"This understanding of how transcription factors can tune gene expression is incredibly important, and we hope to use it to help us treat various diseases in the future.

"If we think about cancer, mutations in cancer can prevent a transcription factor from choosing the right components to express a gene correctly, it's as if the parts of a car were mixed up and it could no longer work reliably."

Dr Charles Bell, a postdoctoral researcher at Peter Mac, said they had developed a platform to screen the function of thousands of components used by transcription factors to determine how a gene is expressed.

"We will now use this platform to understand other processes involved in gene expression," he said.

"The answers to these questions will help us find new ways to treat not only cancer, but also many other diseases in the future."