Here comes the ‘era of proteomics’: A technology that analyzes proteins in record time brings personalized medicine a step closer

• Large-scale proteomics equipment paves the way for the possibility of analyzing patient proteins to guide treatment, as is already the case with genetic information.
• At the National Cancer Research Centre (CNIO) the most advanced proteomics equipment currently available is now in operation.
• “This equipment is another step towards personalised medicine,” explains Marta Isasa, a researcher at CNIO. “Proteomics tells us why the same therapy cures some patients and not others”

Medical treatments are increasingly adapted to the genetic traits of patients, because more and more is known about the relationship between genes and disease. Now medicine is about to take advantage of another great source of information about the functioning of the body: proteomics.

Proteomics analyses the proteins present in cells and tissues at any given time. It has traditionally been a discipline for research, but the development of more sensitive and faster equipment is also making proteomics a useful source of information for treating patients.

One of these new pieces of proteomics equipment, an ASTRAL Orbitrap mass spectrometer, has just been put into operation at the National Cancer Research Centre (CNIO). “It is another step towards personalised and precision medicine,” explains Marta Isasa, head of the CNIO Proteomics Unit.

It is much more sensitive and faster than previous equipment, which allows for “large-scale proteomics,” says Isasa. And this ability to analyse more and better paves the way for the information provided by proteomics to reach clinic practice.

For example, proteomics “allows us to monitor patients from when they are diagnosed, to know how they respond to treatment. And it will be possible to understand why the same therapy cures some patients and not others,” adds Isasa. (Instagram reel).

“The Next Big Revolution”

Proteins are our bricks and our nanomachines, the biomolecules that give structure to the body and make everything work. Proteins are antibodies, hormones, neurotransmitters; the raw material of bone, connective and muscle tissue; the molecular targets on which drugs act… There are a million different proteins in the human body, and studying them provides key information for medicine.

“Proteomics is the next big revolution,” says Isasa. The first was genomics. A decade ago reading (or technically speaking sequencing) a genome to extract information in genes was a sophisticated and expensive process, but advances in sequencing equipment have made the process almost routine. In proteomics, the technological leap is happening now.

The new ASTRAL Orbitrap at CNIO’s Proteomics Unit “is an exponential change,” says Isasa. “Before, to reach 10,000 quantified proteins we needed almost two days of instrument time; now we do it in an hour.”

This type of equipment brings proteomics closer to hospitals, “as a new tool to understand what is happening in the body, and so detect diseases or find treatments. Proteomics will be a key tool in clinical practice,” says the CNIO researcher.

Many more proteins than genes, and constantly changing

Completing the human proteome is difficult not only because there are many different proteins, but also because the number of proteins present in the body at any given time is changing all the time.

“Some proteins are made and serve their purpose in minutes, then the cell breaks them down and recycles their components. Others last several days. In a cell, there may be thousands of proteins at any given time, but these will change drastically according to our needs, throughout the day,” explains Isasa.

The orders for the body to make its proteins come from the genes, in the DNA molecule that is in the nucleus of each cell. For decades it was believed that each gene ordered the production of a single protein, but a few years ago a mystery emerged: the human genome only has around 25,000 genes, but in our body there are a million different proteins.

“The same gene can lead to many different proteins”

After the initial confusion, it was discovered that the genome is only the first level of complexity in the code that describes an organism. Information written in genes is not enough to construct a person; the way that information is translated into proteins adds another level of complexity, which also needs to be deciphered.

“We now know that the same gene can lead to many different proteins,” explains Isasa. And, moreover, “each of these proteins undergoes chemical changes after being manufactured, and those changes called post-translational modifications determine the function and activity of the protein at any given moment.”

Why proteomics is useful in medicine

The information contained in genes is not enough to understand what is happening in a cell. “This is what proteomics tells us,” adds Isasa, who studies how many proteins are in a sample and what they are, whether they have changed and/or interact with other proteins.

Modifications and interactions of proteins vary in the presence of disease, or in response to treatments. Proteins interact with each other according to their shape, fitting together like the pieces of a three-dimensional ‘tetris’. For example, a drug is only effective if it fits with its target protein.

That is why proteomics is essential to validate and discover new pharmacological targets, and to understand the mechanism of drug action or the appearance of resistance. “The applications, both in basic and translational biology, are infinite,” says Isasa.

And she offers a metaphor to help explain her point: “by deciphering the human genome we have discovered the alphabet of life; now, with proteomics, we can begin to understand the whole language.”