A new study, conducted by an international team of researchers, has constructed the largest cellular proteomic map to date, which could pave the way to new disease insights and treatments. The study, using yeast cells as model organisms, shed light on previously unknown genes and investigated how the proteins that genes encode are expressed and regulated. Despite decades of research, the function of many genes remains unknown, limiting our understanding of common and rare diseases and hindering the development of new therapies. In yeast and bacterial cells, there is a lack of fundamental knowledge required to develop new antimicrobials that are urgently needed to tackle rising drug resistance. Largest Proteomic Study The study, led by members from Charité – Universitätsmedizin Berlin, the Francis Crick Institute in London and the University of Edinburgh, is one of the most extensive proteomic studies in the world. A proteome is all the active protein molecules present within an organism, a certain type of tissue, or a cell under specific conditions and at a certain time. The team of researchers used yeast cells to gain a more accurate and detailed picture of the role of genes that were previously not associated with specific functions. The approach is designed to obtain critical information that will reveal the impact of genetic mutations and help to close diagnostic gaps. Protein Expression and Regulation The researchers’ aim was also to investigate how the proteins that certain genes encode are expressed and regulated, which should also help lay the groundwork for developing new drugs. The study revealed general principles governing the expression of proteins - including identifying for thousands of proteins how their function or biophysical properties related to expression. The research also generated data on previously understudied proteins, resulting in the development of new methods for assigning gene function. Collaboration The study was made possible by a collaboration between research teams at Charité, the Francis Crick Institute, and the University of Edinburgh - who contributed to the study by analysing the large dataset. Labs at Cambridge and the University of Toronto also contributed by pioneering essential proteomic technologies and functional genomics methods used in the study. Future Impact The researchers say that their study will have far-reaching implications for the biosciences. This research has provided critical information on gene function and protein expression, paving the way for future breakthroughs in the field of microbiology. The team is now working on conducting a similar study in human cells, with the goal of generating more information on previously unknown genes. The researchers also aim to link the yeast proteome maps with other molecular data to help develop better antifungal therapies. The study, published in the journal Cell, was funded through Sciex, a mass spectrometry manufacturer, the Biotechnology and Biological Sciences Research Council (BBSRC), Wellcome Trust, the Medical Research Council and the European Research Council. The research has the potential to fundamentally improve our understanding of cell biology, providing new insights into gene function in life forms whose cells have a nucleus, which are known as eukaryotes. The proteomes recorded in the study contain key information about potential new drug targets, providing hope for future treatment options. Dr. Georg KustatscherSchool of Biological Sciences, University of Edinburgh We made use of a collection of yeast strains generated by an international consortium, in which all nonessential genes were missing from at least one strain. We then used mass spectrometry, a technology that can quantify thousands of proteins in parallel, to characterize each of the strains, resulting in the largest proteomic study to date. Dr. Markus RalserSenior author of the study, Director of the Institute of Biochemistry and Einstein Professor of Biochemistry at Charité To our surprise, the study further revealed that the response of a protein to these mutations depends more on its biophysical properties than its function. This opens up a new way of looking at analysis of large biological datasets, which these days are often already collected using advanced sequencing or mass spectrometry techniques, but can still be difficult to interpret. Dr. Christoph MessnerGroup leader, University of Zurich - initially responsible for the study at the Francis Crick Institute Related Links Georg Kustatscher The proteomic landscape of genome-wide genetic perturbations, Cell Publication date 02 May, 2023
