PhD position Biology - structur protein interaction (m/f/d)

The research group of Katja Luck offers the following PhD project:

Protein-protein interactions (PPIs) mediate most cellular processes and are key in understanding disease mechanisms. Various high throughput (HTP) methods map at increasing depth and breadth PPIs, yet do not provide information on how proteins interact with each other. In fact, only for about 5% of all known human PPIs a structure of the interaction has been resolved. This lack in structural information hinders our mechanistic understanding of physiological and pathological processes and limits our understanding of the structural diversity with which proteins interact with each other as well as how protein binding evolves. Experimental approaches will not be able to close this knowledge gap in structural information soon. Artificial intelligence (AI)-based approaches gain huge momentum in the ability to learn from experimental data and make meaningful predictions, taking AlphaFold and its highly accurate protein structure prediction as an example. However, the training of powerful AI tools requires comprehensive and unbiased datasets, which we lack for the prediction of protein complex structures. Many PPIs involve disordered regions that mediate binding, however, due to their conformational flexibility and transient mode of binding, are particularly underrepresented in current protein structure datasets. To advance in our understanding of modes of protein binding involving disordered regions of proteins, how they contribute to human disease, and to generate the data that we need to obtain more potent AI tools, we need novel computational and experimental approaches to efficiently chart the landscape of protein-protein binding.

PhD project: Systematic discovery of novel modes of protein-protein binding involving intrinsically disordered protein regions

This PhD project will combine primarily experimental but also computational approaches to discover novel modes of protein-protein binding and characterize their interaction specificities in a quantitative way. To this end, we will leverage existing expertise in the Luck lab on the use of AlphaFold and other structure prediction methods to prioritize PPIs that are likely mediated by a novel mode of protein binding. A new assay will be implemented enabling HTP identification of interacting protein regions using pooled fragment screens and sequencing as readout. Identified interacting regions will be further validated with site-directed mutagenesis and bioluminescence resonance energy transfer measurements in live cells in 96 well format. High-content screening microscopy will be employed to further characterize interfaces and disease-associated mutations overlapping with these interfaces. A focus on PPIs functioning in mRNA splicing or proteostasis with functional follow-ups is possible via existing collaborations. No prior knowledge in programming or bioinformatics as well as structural biology is required but an interest in learning the basics of those as well as in systematic, HTP approaches would be important.

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

Are you an ambitious scientist looking to push the boundaries of research while interacting with colleagues from multiple disciplines and cultures? Then joining the IPP is your opportunity to give your scientific career a flying start!
All you need is:

• Master or equivalent
• Interactive personality & good command of English
• 2 letters of reference

• Exciting, interdisciplinary projects in a lively international environment, with English as our working language
• Advanced training in scientific techniques and professional skills
• Access to our state-of-the-art Core Facilities and their technical expertise
• Fully funded positions with financing until the completion of your thesis
• A lively community of more than 200 PhD students from 44 different countries

For more details on the projects offered and how to apply via our online form, please visit www.imb.de/phd.
The deadline for applications is 3 April 2025. Interviews will take place at IMB in Mainz on 23 & 24 June 2025.
Starting date: 1 August 2025 - 1 January 2026