The dark interactome – methods for discovering novel protein-nucleic acid interactions from complex samples
Supervision
Timo Sachsenberg
EKUT, 1st Supervisor
Sven Degroeve
VIB, 2nd Supervisor
Objectives
Development of Algorithms and tools for statistical valid identification and quantification of protein-nucleic acid cross-links with a focus on novel cross-linking strategies and protocols. Visualization of cross-linking results in a graphical user interface (GUI).
Methodology
Development will be performed as part of OpenMS the major C++ open-source framework for computational proteomics. Improved algorithms will be wrapped in C# to provide them as Proteome Discoverer nodes.
Required skills
Good software engineering skills. Ideally knowledge of the C++ and C# programming language.
Git-based version control system. If available, please provide a link to e.g. your GitHub account and/or link to past projects in your application.
Ideally, a background in machine learning.
Ideally, knowledge of (computational) mass spectrometry.
Strong command of English.
Expected Results
Validated algorithms and user-friendly user interfaces for the large-scale analysis of cross-linking data for RNA and DNA with proteins and the application to biologically relevant data sets.
Planned Secondments
Host: THERMO (B. Delanghe), Duration: 1 Month; When: Year 2; Goal: Practical programming and translation to industry.
Host: VIB (S. Degroeve), Duration: 1 Month; When: Year 2; Goal: Learn modifications open-search algorithms.
Enrolment in doctoral programs
Ph.D. from the Faculty of Mathematics and Science at Eberhard Karls Universität Tübingen.
References
1. Kramer, K., Sachsenberg, T., Beckmann, B. M., Qamar, S., Boon, K.-L., Hentze, M. W., Kohlbacher, O., & Urlaub, H. (2014). Photo-cross-linking and high-resolution mass spectrometry for assignment of RNA-binding sites in RNA-binding proteins. Nature Methods, 11(10), 1064–1070. https://doi.org/10.1038/nmeth.3092
2. Stützer, A., Welp, L. M., Raabe, M., Sachsenberg, T., Kappert, C., Wulf, A., Lau, A. M., David, S.-S., Chernev, A., Kramer, K., Politis, A., Kohlbacher, O., Fischle, W., & Urlaub, H. (2020). Analysis of protein-DNA interactions in chromatin by UV induced cross-linking and mass spectrometry. Nature Communications, 11(1), 1–12. https://doi.org/10.1038/s41467-020-19047-7