New imaging methods reveal that ribosomes are specialized in protein production

When we think about the plan of life, we tend to focus on DNA – the genetic code stored in each cell in our body. But DNA is only part of history. For these instructions to count, they must be read and transformed into proteins – the molecules that carry out the activities of life.

This is where ribosomes come into play. An average cell of your body contains millions of ribosomes, and they are essential to life.

Ribosomes are molecular machines that read the genetic code and produce proteins, enzymes that feed our antibody metabolism that fight against infections.

Maria Barna, PH.D., an associate professor of genetics, devoted her career to understand how ribosomes work, how they specialize to produce different proteins and how they can guide cells by controlling when and where proteins are manufactured.

Recently, Barna published an article in the journal Science Ceal two new approaches to map the location and behavior of ribosomes – to a single resolution of ribosome never possible.

It is difficult to believe that at one point, like so many others, Barna herself was a skeptical of ribosomes.

How ribosomes have gone from ignorance to

In the past, biologists consider the ribosomes as a passive machine – it has made a touch of genetic material and it will assemble the corresponding protein.

“I will be the first to admit that for a long time, I thought that the ribosomes were not going to be interesting to control the key facets of cell and tissue biology,” said Barna.

Then, the work of Barna and others from the early 2000s have shown that changes in ribosomes have led to unusual development defects and diseases. Barna’s own discoveries have helped to advance the field, showing that ribosomes could be selective, even strategic, on the proteins they produce.

“We think there was only one type of ribosome,” she said. “Now it seems that there could be millions of variations, each with different roles in different cells and layers on regulatory layers that allow ribosomes to play an active role in cell regulation.”

How ribosomes are linked to the disease

Changes in the functioning of ribosomes can have drastic implications for human health. Some examples:

• Babies born with mutations in ribosomal genes often have a serious illness – some lack of whole organs or suffer from bone malformations; Others have serious forms of anemia.
• Conditions such as Alzheimer’s and Parkinson are linked to tufts of poorly folded protein, which can result from a defective ribosome activity.
• Cancer cells often have hyperactive ribosomes to produce proteins that tumors need rapid growth.

New methods of studying ribosomes

The ribosomes are so tiny – and so abundant in cells – which tip the precise models in which they regroup have been difficult with standard microscopy. The Barna team – led by former students graduates Zijian Zhang, PH.D., and Adele XU, MD, PH.D. – Development of two cutting -edge techniques to study ribosomes at an unprecedented level of detail:

• RiboxM (Ribosome expansion microscopy): With this technique, scientists have integrated cells into a special gel and developing them, which makes it possible to zoom in on ribosomes and see how they are arranged with much finer details.
• Alibi (optogenetic proximity labeling): Using light to activate molecular labels in specific and small areas of the cell, researchers can isolate and study ribosomes as a function of their location. This reveals which proteins are attached to them and which genetic messages they read.

“Previously, we could see ribosomes like these blackheads on a whole cell, but could not really differentiate them,” said Barna, “or see how one of them joins forces with each other or with structures in a cell.”

What methods have shown

Using tandem techniques, Barna and her colleagues discovered that ribosomes with a unique form of specialized clusters to produce proteins near their need. For example, the proteins necessary for the production of energy by mitochondria – the powers of the cell – are produced by clusters of ribosomes located very close to mitochondria.

“It really leads to a whole new way of thinking where proteins are made and how,” said Barna.

They also showed, for the first time, how ribosomes are arranged in neurons – a research that could possibly be the key to understanding what is wrong in ribosomes during neurodegenerative diseases.

Why it could change the situation

Until now, scientists have only had rough surveys in the soil level on the activity of ribosomes – like trying to map a forest while standing in the middle. These new techniques are like the launch of high -resolution satellites, allowing researchers to see the landscape of protein production in cells with remarkable clarity.

The initial data collected with Ribox and Alibi support the growing evidence that ribosomes are not all created equal – their composition can vary between cell types and even in a single cell, affecting proteins made when and where.

The cartography of ribosomes at this end could change the way we understand and deal with many diseases. By identifying where and how ribosomes work – and dysfunction – researchers can start developing therapies targeting ribosomes of ribosomes without disturbing protein production throughout the body.

Following for the study of ribosomes

The Barna laboratory plans to further refine their tools to capture Ribosome activity in more detail and in more diverse cells of cells.

They hope to study how the composition of ribosomes and clusters change in response to various environmental diseases and conditions. Barna also hopes to understand how the composition of ribosomes and activity change with aging – a moment when protein production becomes more subject to errors and less effective.

Barna said other researchers have already asked questions about the use of Ribox and Alibi, and she hopes that the methods will continue to gain ground.

“This establishes a new bar for the level of detail and resolution which should be expected during the study of ribosomes from now on,” she said.