Researchers at ETH Zurich have a developed an unprecedented tissue-specific atlas that maps the protein-protein interactions taking place inside of the human body. Professor Pedro Beltrao serves as the director of this unique and innovative resource. It prioritizes candidate disease genes by providing greater certainty about the interaction of proteins in various tissues/organs, thus elucidating their functionality.
Our groundbreaking work has revealed the complex interplay between crucial proteins that underpin cellular health and disease. It was circumspectly released in the journal Nature Biotechnology. The scientists explored connections between these relationships in eleven diverse tissue types. In the memorialization of their efforts, they produced a detailed, unpublished map that included the varying protein associations across all tissues. With this atlas, biomedical research will be profoundly revolutionized by facilitating higher quality identification of disease-causing proteins.
Insights from the Research
Beltrao and his team used sophisticated bioinformatics tools and public libraries of proteomic data to trace the inferences of tissue-specific protein interactions. As such, scientists depend on the atlas as a critical resource. This gives them capacity to understand how proteins are interacting in different cell types. A deeper understanding of these interactions can further illuminate the molecular underpinnings of a myriad of diseases and point towards more targeted therapeutic strategies.
“Proteins engaging in teamwork usually influence the same disease,” said Beltrao, emphasizing the significance of these cooperative interactions in understanding disease mechanisms. The breadth of this research provides valuable lessons that can reshape how researchers tackle the study of complex diseases.
The complex tapestry of the human body—its thousands of distinct cell types, with their interwoven signaling pathways to which proteins belong—requires a more sophisticated understanding of protein function. Beltrao noted that “if we know the specific protein interactions, we can better understand what distinguishes a liver cell from a brain cell.” This understanding allows us to understand how to tell healthy from diseased states apart. In doing so, we’re able to create more targeted diagnostics and treatments.
Distinct Protein Interactions in Tissues
The researchers identified that some protein interactions are restricted to specific tissues only. For example, an interaction could only be found in liver tissue but not in any other tissues examined. This level of specificity highlights the need to consider context when studying protein functions. In such cases, the atlas provides association scores that quantitatively characterize association between any two provided sets of proteins. It allows for focused investigation of diseases associated with particular tissues.
Current laboratory experiments designed to test these eukaryotic-prokaryotic protein interactions can be cost prohibitive and extremely time-consuming. The new atlas is doing just that and more. It gives researchers an efficient and empowering opportunity to pursue numerous protein association explorations and validations without draining time and resource capital.
Beltrao pointed out, “So if we can say which proteins work together exclusively in nerve cells, for example, we can better define the genes involved in the disease.” This new ability to pinpoint precise protein partnerships gives researchers superpowers. It will immeasurably increase their ability to find genetic causes associated with a multitude of health conditions.
Implications for Drug Development
The consequences of this research go far beyond fundamental science. They could have enormous implications for drug discovery as well. Even modern day pharmaceuticals often show wide-ranging activity. This can lead to off-target effects or unintended side effects in tissues that are unrelated to the therapeutic target of interest. By leveraging insights from the tissue-specific atlas, pharmaceutical companies could develop drugs that target particular proteins within specific tissues, minimizing adverse effects.
And predicting how those proteins interact across different cell types will allow for more accurate and therapeutic strategies to be targeted more specifically. As Beltrao stated, “If we know the specific protein interactions, we can better understand what distinguishes a liver cell from a brain cell.” This understanding might lead drug design in new directions to find more effective treatments with fewer nasty side effects.