What is the proteome and why should we study it?

To effectively develop new therapeutics and biotechnologies, scientists need sound knowledge of how healthy and diseased cells function at the molecular level. Since proteins carry out most of the activities that give cells their functions and identities, understanding what proteins cells contain and how they change and behave over time is critical to achieving this level of knowledge. 

Researchers have understood the importance of proteins in biology for many years. Thus, they have developed many tools and techniques to study them. Their research has taught us much about the composition, structure, and function of many individual proteins. However, cells contain billions of proteins and it is the dynamic make-up and interactions of all these proteins that determine cellular behavior. Instead of studying individual proteins in isolation, to truly understand cellular function, we need to study the “proteome.” This is the complete set of proteins in a given cell or sample along with their abundances and subcellular locations.    

Recognizing the depth and potential insights that can come from studying the proteome, many researchers have made forays into studying it at scale. They’ve developed proteomics techniques and technologies aiming to provide a comprehensive view of the proteome in any sample of interest. Unfortunately, traditional proteomics technologies have only been able to scratch the surface of the full proteome and have not delivered on the promise of this exciting field.  

With the development of cutting-edge nanofabrication techniques, machine learning, data storage, and robotics, up-and-coming proteomics platforms are finally poised to deliver on the promise of the proteome. In other words, the proteomics revolution is here!  

Novel technologies, like the Nautilus platform, are designed to measure the majority of the proteome and provide information-rich but easy-to-understand analysis of protein identity and abundance. The Nautilus platform aims to provide researchers with information on >95% of the proteome of any sample. Having access to this depth of information will enable scientists to explore new horizons in their research. We discuss some of the many exciting applications of proteomics data below.

Monitoring and forecasting changes in health and disease

Prior to observing signs of disease at the whole-organism level, it is likely that the proteome of affected tissues will begin to change. Fluctuations in the proteome can act as biomarkers that predict how patients’ health will change or how they will respond to a treatment. Thus, to forecast changes in health, physicians can measure the proteomes of patient samples to see if anything is going awry. They can then prevent health issues from manifesting, or lower their severity, by prescribing preventative measures.  

For instance, a physician might begin to see proteins associated with heart disease increase in a patient during a routine check-up. To prevent heart issues from manifesting, the physician might put this patient on drugs that lower cholesterol.
 

Similarly, farmers could use proteomics to forecast changes in crop health. For instance, before entire crops begin to die off, farmers might be able to check them for changes in protein abundance associated with viral or bacterial infections. They could then quarantine the infected plants or begin applying protective chemicals throughout the farm and prevent the spread of the disease. This could improve crop yields and enhance food security. 

Using the proteome to understand cellular identity and function 

The DNA in every cell of an organism is more or less the same, but the protein composition of different cells in an organism varies widely. By profiling the proteomes of different cell types, researchers can learn what proteins give cells their functions. Eventually, they may even be able to manipulate the proteome of one cell to turn it into another kind of cell. This will help physicians restore patients to health when they experience organ or other damage. For instance, with knowledge of the proteome, physicians may – one day – be able to generate replacement cells to heal damaged organs.  

Proteome-level information on cellular identity will also be useful in work with other species. For example, humanity currently spends a vast amount of energy and money creating nitrogen-based fertilizers. Interestingly, there are plants that cooperate with bacteria in the soil to create their own nitrogenous nutrients using abundant nitrogen from the air. Researchers could measure the proteomes of these bacteria and the plant cells that interact with them to better understand how they cooperate to pull nitrogen out of the atmosphere. With a better understanding of this process, researchers may be able to give other plants the ability to create their own nitrogenous nutrients and thereby make it possible to grow more food for a growing global population using less fertilizer. 

Determining how the proteome changes in times of disease or stress

Although researchers know the symptoms of many diseases and may know what genes or pathogens drive them, they do not necessarily have a good understanding of the molecular mechanisms of most diseases. That is, they don’t know how diseases alter proteins to change cellular function. Proteomics can reveal how the composition and abundance of proteins change during disease or stress. This will enable researchers to create treatments that counter such changes.  

For example, in a disease like COVID-19, researchers might see that patient samples have an over-abundance of proteins that activate the immune system. They could then prescribe these patients drugs that tamp down the effects of the immune-activating proteins to protect patients from autoimmune damage. 

This will not only be useful in the case of human disease but could also be used to improve environmental health as the planet faces threats like climate change. For instance, scientists will be able to use proteomics to study how various plants’ proteomes respond to climatic conditions like drought. If they find plants that are robust to drought, they can compare their proteomes to those of plants that die off during drought. They may find proteins or sets of proteins that make plants particularly drought resistant. Researchers might then increase the levels of these resistance proteins in drought-susceptible plants and thereby make them more resistant. This could help preserve ecosystem health as the climate changes.

New horizons in protein research

We are only barely skimming the surface of what proteomics can do for applied and basic research across many different fields. Nonetheless, we hope you are convinced that the potential of novel proteomics technologies is vast and largely untapped. In future posts, we will dive into a little more detail on how scientists study the proteome and take a look at the types of biological information they can uncover using various proteomics methods.