Projects Offered

1 PhD project offered in the IPP winter call 2026/2027

Scientific Background

Phosphorylation is a post-translational modification by which kinases attach a phosphate group to proteins or other biomolecules. Phosphate groups are negatively charged and bulky, thus, they substantially alter the local biophysical and biochemical properties of proteins with implications in partner binding and conformation. In a collaborative effort with the Beli lab (IMB) and Gräter lab (MPI-P) we have discovered that in response to various cellular stresses, cells respond with widespread induction of phosphoclusters (close-by phosphorylation events) in intrinsically disordered protein regions (IDRs). How phosphocluster induction is coupled to increasing levels of cellular stress and how phosphoclusters regulate downstream cellular responses is not well understood. By combining expertise in proteomics and molecular biology (Beli lab), with expertise in polymer sciences and molecular dynamics simulations (Gräter lab), and with expertise in omic data analysis and integration, protein structure and sequence analysis, as well as the study of protein interactions (Luck lab), we aim to dissect the dynamics and biophysics of phosphocluster signaling inside cells.

PhD Project: Computational approaches to study the role of clustered phosphorylation and multivalency in cell signaling

As part of this entirely computational project, the PhD candidate will develop a statistical model to identify and score phosphoclusters in protein sequences based on proteomics data generated in the Beli lab. The PhD candidate will furthermore improve in-house software involving machine learning to predict the occurrences of protein interaction sites (so called short linear motifs) in disordered protein regions and determine how they are created or modified by clustered phosphorylation. Attention will be paid to the detection of multivalent and degenerate motif occurrences as one possible mechanism how clustered phosphorylation impacts downstream partner binding and signalling responses. This work will be instrumental in the selection of phosphorylated IDRs and proteins for further experimental study in the Beli lab and for large scale molecular dynamics simulations in the Gräter lab to understand the impact of clustered phosphorylation on the conformational dynamics of the IDRs. Predicted dramatic conformational alterations in phosphorylated IDRs will subsequently be analyzed for possible changes in partner binding elsewhere in the protein chain using AlphaFold and other tools for protein complex structure prediction. We expect to jointly discover principles of phosphocluster signaling in cells, which can be used to predict and redesign signaling circuits in cells. The project is embedded within the collaborative research consortium SFB1551 (crc1551.com, pending funding decision in November 2026). 

If you are interested in this project, please select Luck (Comp) as your group preference in the IPP application platform.

Publications relevant to this project

Conte F, Ostermaier M, Wang J, Goss C, Sayols S, Chen JX, Roukos V, Gräter F, Aponte-Santamaría C, Luck K, Beli P (2026) The phosphoproteomic landscape of the DNA damage response. bioRxivLink

Hubrich D, Alvarado Valverde J, Lee CY, Djokic M, Welzel M, Hintz K, Strom JM, Luck K (2026) Variant characterization in the intrinsically disordered human proteome. Nat Struct Mol Biol. 33(8):1183-1193 Link

Valverde JA, Luck K (2026) Toward Quantitative Domain-Motif Interactomes: State of the Art, Challenges, and Perspectives. Annu Rev Biomed Data Sci. 9(1):337-357 Link

Lee CY, Hubrich D, Varga JK, Schäfer C, Welzel M, Schumbera E, Djokic M, Strom JM, Schönfeld J, Geist JL, Polat F, Gibson TJ, Keller Valsecchi CI, Kumar M, Schueler-Furman O, Luck K (2024) Systematic discovery of protein interaction interfaces using AlphaFold and experimental validation. Mol Syst Biol, 20:75-97 Link

Yu M, Dhiman S, Dormann D, Gräter F, Luck K, Schmid F, Walther A, Lemke EA (2026) Polymer Concepts in Cellular Function. Adv Sci (Weinh). e76934 Link