“This is a field that has really developed just in the last 15 years thanks to advances in mass spectrometry and computation, along with the sequencing of the human genome," says Yue Chen, who joined the College of Biological Sciences faculty this fall.
Chen is a researcher in the rapidly growing field of functional proteomics. It’s the study of the functions of proteins, which are the main components of the physiological metabolic pathways of cells for all living organisms. The name blends the words “protein” and “genome,” making it analogous genomics, another relatively new area of study. According to Chen, “What happens functionally with proteins, and how they change and modify, can help us understand the difference in regulation between cancer cells and normal ones so that we can learn more about cancer-signaling pathways and epigenetic mechanisms.”
Protein’s post-translational modifications
While a genome is relatively constant, proteomes offer incredible variety, with distinct genes expressed in different cell types and in different ways over time. In fact, the human proteome is estimated to contain between 20,000 and 25,000 non-redundant proteins, and the total number of unique human proteins is estimated to range in the low millions.
“My research is focused on ways to further our understanding of protein’s post-translational modifications,” Chen says, explaining that this step in protein biosynthesis extends the range of protein function by attaching it to other biochemical functional groups, changing the chemical nature of an amino acid or making structural changes. While these modifications impact the protein’s function in many ways, he points to his work with histones as an example. Histones, which are a kind of protein found in eukaryotic cell nuclei, package and order DNA into structural units called nucleosomes.
“With histones, some of the modifications can mark whether a region’s genes can be transcribed or silenced, which is called the histone’s epigenetic mark, and which contributes to the phenotypic difference between a normal cell and a cancer cell,” Chen says. “We’re trying to develop technologies to allow us to better identify and quantify the protein modifications systematically and understand their functions within the cellular process. One of the major questions we have now is that with thousands of protein modifications that have been identified, how many of them are really functionally relevant? We’re developing quantitative proteomics technologies to better understand this process and try to identify the modifications as well as regulatory enzymes that are functionally important in cellular pathways and diseases.”
Chen looks back on advances in his field with some amazement. “When I started graduate school, this area of study was just starting to take off,” he says. “Human genome sequencing took things to another level. Now that we’re working with more advanced computer capabilities, researchers have developed more sophisticated algorithms for protein identification and quantification. We also have access to much better, higher-resolution commercial mass spectrometers.” That’s why Chen’s first priority is to seek access to a new mass spectrometer with high acquisition speed and mass resolution for identification and quantification of protein modifications.
Hoping for “noble discoveries”
As he looks ahead, Chen is hopeful that his work might someday have an impact on the identification of potential new drugs for the treatment of disease, by revealing new pathways that may provide treatment targets, and by providing ways to inactivate proteins involved in disease. “I’m passionate about using functional proteomics to make noble discoveries,” says the researcher, who adds that it could have big implications for cancer treatments.
— Julie Kendrick