What is the proteome? What is proteomics? Why do we study it?
Simply put, your proteome is the collection of proteins inside of your body, and proteomics is the study of proteins. This study is incredibly complicated, but it’s considered to be one of the big frontiers facing biology and personalized medicine after the Human Genome project.
We’re increasingly aware of the possibilities of understanding our genome. Really understanding the intricacies of our genome can help us identify all sorts of health problems and how to fix them. But the genome is only part of the story. Think of your genome (the list of Cs, Ts, Gs, and As) like an ingredients list for you. For example, it’s relatively easy to find the problem in the genome that leads to cystic fibrosis. But your genome doesn’t tell you how all of those genes come together to interact and develop.
In many cases, you can’t look at a genome to see what’s wrong with a sick person. Your genome is your predisposition, but it’s not the whole story. If you’re trying to find out why you’re sick, you don’t necessarily want to know about predispositions. You want to know about what’s going on in your body right now. You need to look at what the genes are producing.
Genes produce proteins. The proteins in your body, when studied collectively, are your proteome.
Unfortunately, it’s very difficult to measure and make sense of a proteome for several reasons:
When I say protein, you probably think of muscle development and thick shakes for post-workout consumption. But they’re much more than that!
Proteins perform a huge variety of different tasks within the body. Yes, proteins help build muscle. But they’re also integral to DNA replication, cell structure, and moving nutrients around within your body.
Proteins, essentially, are the “doers” of the cell. Most other biological molecules (except for RNA) are inert. Proteins do almost all of the work to translate genetic coding into everything else.
They do this by binding to other molecules and even other proteins, activating or deactivating extremely specific aspects of a molecule or membrane. There are a variety of different functions of proteins:
The proteome is the direct product of your genome. Your genome is a set of instructions for creating proteins. All coding genes are expressed through the production of different proteins, each with their own specialized job.
The process of moving from genome to proteome occurs in two main steps.
Each protein has a gene at a particular location on your genome. Each cell of your body contains an exact copy of your entire genome. The recipe for stomach enzymes is not only stored in your gut but in every cell of your body. However, our skin does not produce acid and digestive enzymes. The process of gene transcription is highly regulated to control where different genes are expressed.
Depending on where in your body this particular cell is, different genes will be active. Some genes hide on the inside of your chromosome. Other genes have specialized proteins attached to them to up or down-regulate their expression. Some genes receive a methyl group, turning them off. These regulators allow the cells in your liver to be different from the cells on your feet. These changes are called epigenetic modifications when they are passed on between cells or generations.
The first step towards creating a protein is to make a copy of the gene. This process uses an enzyme called RNA polymerase. This protein binds to your DNA, unzipping the strands as it moves along the gene. This copies your DNA into RNA, a similar more portable molecule. Think of this like moving a file from your hard drive to your flash drive. It’s stored in a new way but contains the same information. We call these copies messenger RNA (mRNA).
The next step is where the real magic happens. The translation is the process through which genetic information (nucleic acids) becomes a protein. This process is at the core of what enables life as we know it.
The mRNA is encoded in three letter chunks, called codons. Each of these codons represents a particular amino acid, the building blocks of protein. This sequence of molecules represents the primary structure of the protein.
Translation occurs with the help of other proteins called ribosomes. These proteins bind to the mRNA at the first codon. The three nucleotides act like a key, changing the shape of the ribosomes. Each codon changes its shape to grab a specific amino acid. It grows a tail of amino acids as it moves along the RNA.
At this point, the protein is just a long strand of amino acids. The function comes from the complex three-dimensional shape it folds into. The interactions of the amino acids define the shape of the protein. Specialized enzymes and RNA assist the protein to fold into the correct shape. This folded protein forms an intricate molecular machine.
Transcription and translation make up the essential elements of gene expression. These two steps are essential for all life. However, these two steps are not all that happens in gene expression. Real world gene expression is far more complex.
Various other steps are often involved to create a functional protein. Modifications to mRNA and proteins are essential. Many of these changes allow for more complex proteins. We call these post-translational modifications.
Many genes create RNA that never becomes a protein. These non-coding RNAs can suppress gene expression, assist in protein folding, and more.
The complexity of going from the genome to the proteome exposes how important it is. The proteome is the product of many complex interactions. This complexity is why understanding the proteome reveals what the genome does not. Unlike your genome, your proteome controls your bodily functions in real time.
Though we understand the importance of the proteome, reading the clues it holds is difficult. The proteome varies from tissue to tissue. It even varies between parts of a cell. Environment, diet, exercise, and much more can all influence the proteome. These changes influence the levels of thousands of different proteins. As a result, weeding out the signal from the noise is no easy task.
Currently, studying the proteome requires advanced techniques and technologies. However, researchers are working to develop simple tests that take advantage of the secrets in our proteome.
Studying proteomics presents many challenges. Researchers and lab technicians need to take a complex sample like blood or tissue and determine the proteins inside. This sample is rich with other, less useful things. These include sugars, ions, fats, and even proteins which can make processing, purifying, and quantifying samples difficult. In addition, the proteins of interest could be hundreds of times less common than other proteins. To combat these difficulties researchers have developed many techniques to extract, separate, identify, and quantify proteins. We cover a few of the most common techniques below.
SDS-PAGE stands for sodium dodecyl sulfate-polyacrylamide gel electrophoresis. What a mouthful! Simply put, this technique separates proteins by mass. It does this by loading the purified samples into a gelatin-like material called polyacrylamide. Next, the electrical current pushes the protein through this gel. Each protein moves at a different speed depending upon its weight. This leaves distinct bands of protein, sorted by weight.
Two-dimensional electrophoresis (2DE) is very similar to SDS-PAGE. The difference is, unsurprisingly that the proteins move on two dimensions. First, you separate the proteins by mass. Next, you separate them by electrical charge. This allows for far better separation of individual proteins.
Mass spectrometry is another technique that allows identification of individual proteins. It is far more accurate and sensitive than gel-based techniques. It is also more expensive and requires more purified samples.
The data produced by proteomics research is massive. Proteomic experiments record complex information about the proteome in different organisms, body parts, and conditions. These data are often shared in large online protein databases. As data science tools improve and scientists develop new techniques, existing data will reveal new patterns and discoveries.
Reading the protein levels of a person, organ, or individual cell at a given point in time can tell us a lot about what’s going on at that moment. While reading a genome can tell us if someone’s predisposed to a disease or ailment, reading their protein levels can tell us what’s going on right now. A few examples of how we can use proteomics include:
Malignant transformations within a cell alter the protein expressions of that cell. In other words, doctors can detect early stages of cancer by looking at the proteome. The specific protein signatures of a cancer will help doctors diagnose, prognose, and treat more effectively. There is still much work to be done in understanding protein arrays before this is a reality, though (Shruthi et. al., 2016).
How aggressive is a tumor? Some tumors grow aggressively and metastasize easily, while others grow slowly and never metastasize. Currently, we treat cancer as a single disease despite these obvious and important differences. Proteomics can help researchers and doctors identify which tumors and patients require the most aggressive treatments available versus more moderate approaches. This will help prevent over-treatment (as cancer treatments are often unpleasant, to say the least) for many and may help get the most aggressive treatment to those who need it, faster.
Cardiovascular disease is one of the leading causes of death worldwide, despite many efforts to understand and treat it more effectively. Proteomics can help researchers and doctors understand inflammation, wound healing, and handling of cholesterol in the heart. Eventually, pairing proteomic research with other areas of research should help researchers develop drugs that more effectively treat this disease (Mokou et. al., 2017).
Early research suggests that we can use protein levels to identify quantitative trait loci (QTL). QTL are segments of DNA that correlate with one or more observed traits. These protein levels do not necessarily correlate with the amount of mRNA for that protein. Factors such as modifications to the protein and mRNA play a large role in controlling gene expression. The factors at play in gene expression are complex. Looking at the actual proteome is the only way to know the final result (Stylianou et. al., 2008).
Proteomics will help us understand how proteins are made, how they degrade, how they are modified, how they’re expressed, how they make changes in the body, how they interact with each other, and how they move around the body. Ultimately, understanding all of these aspects of our proteome will help humans prevent and treat more diseases more effectively.
Your proteome contains a wealth of information. Every function of your body relies on many proteins. When you are sick, your proteome changes. Consequently, most drugs target specific proteins. Understanding the proteome helps us understand the how and why of diseases. Therefore, proteomics research is extremely important to healthcare.
The vast majority of drugs work by binding to a protein and adjusting its function. Drugs fit into specific locations in a folded protein. The fit is like a key in a lock. The structure of the drug must perfectly compliment the site it binds to.
Understanding the proteome associated with a disease helps researchers develop targeted drugs. By finding changes in proteins associated with the disease, researchers can develop drugs targeting these proteins.
The massive amount of data available about proteins and chemical structures can be used to discover new drugs. Dr. Tim Haystead at Duke University is using this technique to find new malaria treatments. By using computers to determine which proteins drugs bind to, he can discover the causes of side-effects as well as the intended targets. This helps develop more effective drugs with fewer side effects.
Screening proteins in blood and urine can provide important diagnostic insight. Your proteome responds to disease. Taking a look at how the proteomes of a healthy vs. sick person differ can provide insight into the cause of the disease.
Differences in protein can also be used to identify diseases early on. Protein levels may change before symptoms become apparent. Once we know how the proteome responds to a disease, we can start looking for those changes.
Screening for ovarian cancer is already using these methods. Diseases like this are often difficult to detect. Proteomics has the potential to identify biomarkers for many diseases. Eventually, this will enable simple tests to identify diseases at the earliest stage possible.
The end game of proteomics is to create completely personalized medicine. Researchers hope that we eventually will be able to prevent many diseases by monitoring and adjusting patients proteomes. By understanding the exact changes occurring in a patient, doctors will be able to personalize treatment. This will enable far better outcomes for diseases like cancer and Alzheimers.
The proteome is a complex system involved in every human function. Researching proteomics helps us understand health and disease. Because proteins are the actual “doers” of the cell, they can teach us far more than genes. They are also far more difficult to study. However, improving technologies and growing data are now allowing us to apply our knowledge of the proteome to human health. Proteomics opens to door to a whole new world of personalized medicine and rapid diagnosis.
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