What Can We Learn from Proteomics: An Expert Interview with Morgan Bailey

Most people have heard the term genomics, the study of an organism’s DNA. Genomics has led to the development of advanced medicines, including gene therapy, genetic testing, and disease prevention. But there is little public discussion around proteomics, a similar study. In simple terms, proteomics is the large-scale study of the proteome, which is the entire set of proteins that make up each living organisms. An emerging field in the biological sciences, proteomics is useful because it can reveal significant information about the cellular processes behind early signs of disease, autoimmune disorders, cancers, and metabolic issues. It can even elucidate the protein targets of different molecules. 

Dr. Morgan Bailey, a research chemist at RTI, conducts proteomic analyses to better understand how proteins respond to environmental contaminants like PFAS and microplastics. We sat down with Dr. Bailey to learn more about his work with proteomics and the implications it has on human health.

What is proteomics and why is it important? 

In 1975, three scientists performed the first “proteomic” experiments on three different organisms (E.coli, mouse, and guinea pig) using a technique called two-dimensional gel electrophoresis. The proteins from each organism were able to be separated; however their identities were unable to be easily identified. It was not until the early 1990’s that mass spectrometry was used for protein identification and has become an invaluable proteomic technique. The capabilities of mass spectrometry and its associated techniques have only improved since the 1990’s with better sensitivity, accuracy, and the ability to analyze very complex protein mixtures. 

It is well established that proteins are the functional products of genes and are one of the essential building blocks of life. Like genes, proteins can have altered expression levels due to a host of environmental factors. However, the most important feature of proteins is their structure, which determines their biological function. Therefore, proteomics not only gives us information about which proteins are upregulated and downregulated but provides information on structural changes that help us better understand the molecular mechanisms of life. 

Proteomics provides fundamental insights in the study of human health. Here are some key applications:

• We can use biomarker elucidation to differentiate disease states – for example, to tell a cancerous cell from a healthy cell, or distinguish among different subtypes of cancer.
• We can identify protein targets of small molecule drugs, which are used in targeted therapy for cancer.
• We can explore protein interactions with other biological macromolecules (e.g. protein-protein, protein-DNA, protein-RNA interactions)
• We can identify post-translational modifications (e.g. phosphorylation and ubiquitination) that alter a protein’s structure and ultimately its function – the underlying chemical processes in diseases such as cancer and Alzheimer’s.

It is important to note that proteomics can span multiple scientific disciplines. Proteomics should be used in conjunction with other experimental approaches such as genomics and metabolomics to truly understand the biological system you are studying.

What made you want to study proteomics?

When I was growing up, I would learn about family members who had passed away due to terrible diseases that to this day continue to plague millions around the world. I always had a curiosity for how these diseases started and how we could treat them, which eventually inspired me to become a scientist. While studying chemistry as an undergrad, I took a biochemistry course that taught me how proteins are one of the fundamental building blocks of life and are important in human health. I learned that the structure of each protein determines its biological function and that a change in this structure could lead to disease development. 

Towards the end of my undergraduate career, I attended an ACS (American Chemical Society) conference and learned about mass spectrometry and proteomics. It was there that I realized I could combine my interest in analytical chemistry with my passion for understanding how diseases develop and how to treat them. This ultimately led me to pursue my PhD in proteomics and mass spectrometry at Duke University. Since then, I have learned that proteomics can be applied to multiple different scientific disciplines, and I am continuing to pursue my passion here at RTI.

What proteomics projects are you currently working on? 

The first project I was tasked with when I joined RTI was to reestablish and expand the institute’s current proteomics capabilities. I have established a robust non-targeted quantitative bottom-up proteomics workflow that utilizes liquid chromatography tandem mass spectrometry (LC-MS/MS). Now my focus is to develop targeted proteomic approaches that can validate the results obtained from the non-targeted analyses. I am hoping that by advertising these capabilities we can encourage more internal and external collaborators who are interested in applying these approaches to their own work.

 I am currently applying the established non-targeted proteomic analyses to two different toxicological projects. The first is trying to understand the cytotoxic mechanism of the chemicals found in tire rubble particles on human lung cell models in collaboration with metabolic and in vitro studies performed by Dr. Imari Walker Franklin and Dr. Leslimar Ríos-Colón at RTI. 

I am also using our current proteomic approaches to supplement metabolic and exposomic studies on the effects of ephedra sinica on liver cells. Similar to the goal of the tire rubble study, using proteomics in this work will provide us with a better understanding of the cellular response to this FDA banned botanical product. The preliminary data from these projects has also generated exciting new projects that are currently in the planning phase.

What does proteomics tell us about the effects of emerging contaminants like PFAS and microplastics?

Emerging contaminants have been a growing concern to human health as new research presents the effects of the toxic byproducts that come from the materials we use daily. Although there are plenty of studies describing the harmful effects of these chemical byproducts, there is limited research on their toxicological mechanism. The goal of applying proteomic analyses to emerging contaminants research is to understand how our cells and the biological pathways that keep us alive respond to these environmental toxins. We can use proteomics to elucidate protein markers to not only help us track exposure but also identify early signs of disease development from different exposure scenarios. Proteomics can also be combined with other in vitro and omics studies to encompass different aspects of a toxicological response. By fully understanding each toxin at the molecular level, we can provide novel solutions and potential therapies to mitigate the effects of our exposure. 

What is your hope for the future of proteomics studies?

Within the past decade there have been numerous studies highlighting new or improved proteomic capabilities. However, we must continue to look for novel ways to obtain more protein identifications in a shorter amount of time. Current approaches must balance time with coverage depth, which usually results in a sacrifice in one or the other. As the need for more niche protein targets rises, the proteomics field must adapt to meet this demand by improving the current sample preparation, instrumentation, and data analysis software.

A large majority of proteomic studies are focused on the expression level of proteins in different sample conditions. There is not a direct link between protein expression and protein function. This ultimately makes finding and validating a functionally relevant protein target very challenging. However, there is a connection between how a protein is folded and its biological function. Therefore, my hope is that we can prioritize using protein folding stability measurements to identify functionally relevant biomarkers in conjunction with conventional protein expression level studies to better understand the proteome and its changes.