FMI senior group leader Jeff Chao and his group have been awarded a €2.5 million European Research Council (ERC) Advanced Grant for ImagineRNA, a project that will use advanced microscopy to study how gene expression is controlled inside living human cells. ERC Advanced Grants support established researchers and their teams as they pursue ambitious, high-risk research projects.
The ImagineRNA project aims to uncover fundamental principles that help cells regulate gene expression — the process by which information in genes is used to make functional molecules such as proteins. To do this, the team will examine what happens when biology is pushed to the extreme: across distance, over long periods of time and at the level of single molecules.
At the heart of the project is messenger RNA, or mRNA for short. These molecules carry genetic instructions from DNA to the cellular machinery that makes proteins. But mRNAs are not simply passive messengers. Where they go, when they are used and how long they survive can shape how genes behave.
Chao’s group will engineer stem cells grown in the laboratory so that individual mRNA molecules can be followed under a microscope. These stem cells can also be coaxed into becoming different specialized cell types, allowing the researchers to ask how RNA behavior changes in different biological settings.
One major focus will be nerve cells. Neurons are highly compartmentalized: their main cell body can sit far away from the dendrites and axons that receive and send signals. The team will investigate how mRNAs are controlled both close to the nucleus and at distant sites in these long cellular projections, where proteins often need to be made locally and at the right time.
Another focus will be muscle cells, which express some of the largest genes in the human genome. Producing a single mRNA or protein from these genes can take hours, creating unusual challenges for keeping gene expression accurate over time.
The project will also push the resolution of RNA biology by directly observing interactions between single proteins and mRNAs inside cells. Watching these molecular events one by one could provide a new way to understand how biochemical reactions unfold in their natural cellular environment, including how mRNAs are translated into proteins or targeted for decay.
Because neurons and muscle cells face distinct challenges in maintaining faithful gene expression, ImagineRNA will also explore how mistakes in RNA regulation may contribute to disease, including neurodegeneration and muscle disease.
By making RNA behavior visible in living cells with unprecedented detail, the project could reveal basic rules that help cells regulate genes in health and disease.