Open Modification Searches Facilitate the Study of Protein Modifications Including Glycosylation in Haloferax volcanii

Students

Faculty

Professor of Biology

Project Summary

After their biosynthesis, proteins can be further processed and modified. These so-called post-translational modifications (PTMs) vastly increase the complexity of the proteome, as one gene can lead to a multitude of protein isoforms with different structures, localization or function. For instance, glycosylation, the addition of carbohydrate molecules to a protein, has been shown to be involved in the formation of biofilms, microbial communities that can be up to 1000 times more resistant to antibiotics than individual organisms. However, due to their complexity, PTMs are difficult to analyze and only recent developments of bioinformatic tools have allowed getting a more comprehensive view on the role of PTMs.

In this project, I analyzed mass spectrometric data of cellular fractions from the model archaeon Haloferax volcanii using recently developed algorithms to search for all possible modifications within a wide mass range, called open modification search. In comparison, a closed search is performed, which takes into account only a limited number of specified modifications.  The results showed that the open search approach allows for the identification of modified peptides that were neglected by the closed search. In addition, the open search was able to identify glycosylated peptides, which, due to their complexity, are often not taken into account. Therefore, open searches could represent a new approach to include the analysis of glycosylation in a standard proteomics workflow. As a result of this research project, the pipeline set up for the open search can be used for functional studies in a variety of organisms. 

Working on this project has increased my interest in computer science, as I was able to experience an example of its direct application in other fields. I have learned to not only use bioinformatic tools to contribute to answer research questions in biology, but also what it means to do research in bioinformatics itself. In the future, I look forward to continuing working on this project and I am excited about the potential applications of its results.