Revealing protein function through highly sensitive single-cell proteomics

I'm Daniel Hornburg. I'm the VP for Biomarkers and Precision Medicine at Bruker.

By functional proteomics 2.0, we mean that we are not only cataloging proteins, but we are actually trying to understand what they do. So every protein has a specific function, and actually, every gene can express many different protein forms that then exert different functions that connect to your health state, that connect to certain diseases.

And by cataloging and measuring the functional proteome, we understand what really happens in every single cell and what really happens when you are getting sick, and how this is changing over time.

With the timsAUTO AIP, we have probably the most sensitive mass spec on the planet, which enables us to really look into every single cell, the smallest immune cells, understand whether they are activated, whether they are attenuated. And that's super relevant when, for example, we look at cancer, where the interplay between the cancer cells and the immune system is really dictating whether we can fight off the cancer or not.

Another level that the mass spec can explore, which is very unique and different from sequencing approaches, is to look at, for example, what is expressed on the outside of a cancer cell. So a cancer cell presents itself to the immune system, but it tries to hide also from the immune system. So measuring which protein fragments are on the surface of a cell, which requires a huge amount of sensitivity, allows us to understand why certain cancer cells can evade the immune system. And here, really, the sensitivity of that instrument is a differentiator.

There are many biological insights that are unlocked by mass spectrometry, especially those that are functionally linked to your phenotype, because proteins are so much closer to the phenotype. In contrast to the DNA, which always just tells us what could be, the proteome is telling us what actually is happening in every single cell, what's happening under every single physiological or pathological state.

So, for example, a cancer cell, it expresses its own proteome on the surface, and the immune system can monitor the surface of these cells and understand this is a cancer cell, or this is a normal cell, and sometimes that doesn't happen, and that's when the cancer can spread.

So deploying proteomics allows us to monitor what actually helps the cancer to evade the immune system and how we can help the immune system to find the cancer.

Another approach is to, for example, identify how proteins and drugs are interacting. Again, drugs are usually targeting protein or metabolic pathways in order to correct for something that goes wrong. With mass spectrometry, we can actually monitor how the drug is interacting, and we can design and identify new drugs that only work on the protein of interest and not doing anything else in the cell, which is the ideal setting. We are not having any side effects.

And only with mass spectrometry, we really have the transparency on all of these biological processes.

How does highly sensitive mass spectrometry advance functional proteomics?

Highly sensitive mass spectrometry moves beyond cataloging proteins to reveal their functions, forms, and changes within individual cells. According to Bruker’s Daniel Hornburg, functional proteomics connects protein activity with health, disease, and changing physiological or pathological states.

How can the timsUltra AIP platform provide insight into cancer immune evasion?

The timsUltra™ AIP platform can analyze small immune cells and protein fragments displayed on cancer-cell surfaces. This sensitivity helps scientists determine whether immune cells are activated or attenuated and investigate how cancer cells hide from the immune system, evade detection, and spread.

How does mass spectrometry support drug-target interaction research and precision medicine?

Mass spectrometry can monitor how drugs interact with proteins, small molecules, and metabolic pathways. These functional proteomics insights help researchers identify drugs that act specifically on the protein of interest without affecting other cellular processes, supporting precision medicine and the goal of reducing side effects.