Postdoc: The Single-molecule Biophysics of Ribosome Cooperation

Postdoc: The Single-molecule Biophysics of Ribosome Cooperation

Institute AMOLF

Amsterdam, Netherlands

Summary

In this project, you will perform innovative (bio)physics experiments to elucidate the dynamic action of individual ribosomes. The key methodologies are optical tweezers and single-molecule fluorescence, as well as selective ribosome profiling – an exciting new RNA sequencing method. Working in the Tans biophysics lab @ AMOLF Amsterdam, you will visualize the real-time translation activity of ribosomes, how multiple ribosomes work together, detect the folding of individual polypeptide chains, and show how chaperones guide this process. You will work in an international team, with other groups specialized in ribosome profiling and cryo-EM techniques. The aim is to elucidate the fundamental mechanisms that underlie the correct and erroneous production of new proteins.

Questions

According to textbooks, ribosomes work individually to produce proteins. However, recent insights from our lab and others show multiple ribosomes cooperate as they translate mRNA. This cooperation may well be essential to produce multi-protein complexes faithfully. In our group, we aim to elucidate the highly diverse and broad implications. Questions include: Do ribosomes synchronize their translation activity in real-time, like a sequence of cars in traffic? Are mRNA secondary structures and/or direct interactions between ribosomes involved? How do the two (or more) protein chains synthesized by these multiple ribosomes fold together to form protein complexes? How many ribosomes cooperate together? Can we see cooperation between ribosomes that translate different RNA messages? Given the novelty of these fundamental questions in this rapidly expanding field, you will have a unique chance to address them first.

Approach

You will directly follow the unknown dynamics of ribosome translation, protein folding and assembly, and chaperone guidance. This is enabled using optical tweezers combined with single-molecule fluorescence, which detect changes in individual molecules at nanometer and millisecond resolution. In collaboration with our partners, you will also use selective ribosome profiling – an RNA sequencing method that provides high-level data across the genome an in-vivo. This first look may reveal a host of unexpected phenomena. You will develop new experimental schemes, Use cutting-edge single-molecule fluorescence and manipulation methods, Adapt existing biochemical protocols, Analyze the complex temporal data, formulation of new models, And explain your findings in high-level scientific papers.

Qualifications

We have a number of positions available (PhD and PD). We are looking for outstanding experimental physicists or chemists with an interest in single-molecule techniques, ambition to make breakthrough findings, programming skills to handle complex data, and who thrive in a diverse, collaborative, and supportive environment. Excellent verbal and written English skills are essential.

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