Completed Genetics & Molecular Biology Cells, Biochemistry & Physiology

Post-transcriptional control of gene expression following toxic injury

In plain English

AI plain-English summary

When a cell is poisoned by a toxic chemical or chemotherapy drug, it doesn't just sit there—it changes which proteins it makes and how fast it makes them. This project studies that rapid, life-or-death reprogramming of protein synthesis. The problem is that we know very little about how cells decide to speed up, slow down, or switch the types of proteins they produce after a toxic injury. The abstract describes ribosomes as "molecular factories" that decode messenger RNA (mRNA) to build proteins, but the rules governing when and how those factories retool in response to harm remain largely unknown. Without that knowledge, we cannot predict why some cells survive a toxic hit while others die, or why certain chemotherapies work in some patients but fail in others. This is fundamental science. The researchers are not developing a drug or a diagnostic today. They are mapping the control system that sits between a cell sensing danger and the cell making the proteins needed to cope. If successful, this work could eventually inform better strategies for protecting healthy tissue during chemotherapy, or for designing toxins that more reliably kill cancer cells. Past discoveries in how cells regulate protein synthesis have already led to drugs that target the ribosome in cancer and infectious disease—this project aims to fill in the missing rules of that same system.

View original technical description
Protein synthesis is the process by which the information in the genetic material in the cell, DNA is converted via an intermediary substrate called mRNA, into proteins. For proteins to be made the mRNA must interact with a large complex called the ribosome which consists of RNAs and proteins. Ribosomes can therefore be thought of as “molecular factories” that make proteins. They do this by decoding the genetic information that is held in the mRNA and bringing all the building blocks together to synthesise proteins. The rate at which proteins are made is very highly regulated and cells respond to alterations in the external environment, such as exposure to toxic chemicals and chemotherapeutic agents by modifying both the rate at which they make proteins and importantly the types of proteins that they make. We are studying these processes to gain a greater understanding of the cells/organisms response to toxic insult.

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Researchers

Anne Willis (Principal Investigator)

Related Research

Grants with similar aims, by meaning.

The role of the RNA regulon in the control of gene expression
Post-transcriptional regulation of gene expression following toxic injury
Investigation of the selective reprogramming of translation during apoptosis
Regulation of protein synthesis by elongation control in health and disease
How internal interactions between the processive phases of eukaryotic protein synthesis control flux through the overall system

Original classification

Intramural

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