Postdoc: Revealing ribosomes using single-molecule and RNA sequencing

Work Activities

Summary - In this project, you will perform innovative (bio)physics experiments to elucidate the dynamic action of individual ribosomes - specifically their interactions within polysomes. The key methodologies are optical tweezers, 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 within larger ‘polysomes’ may well be essential to produce multi-protein complexes faithfully. In our group, we aim to elucidate the highly diverse and broad implications. Questions we are interested in 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.

International team - You will be part of a collaboration with leading groups at Heidelberg University and the ETH in Zurich, which use novel sequencing and cryo-EM methods. By working within this motivated group of young scientists, you will obtain a unique training, understanding and skill set in this expanding field. By integrating these approaches, you will provide insights of unprecedented detail, spanning from the cellular to the atomic level, from in vivo to in vitro, from genome-wide patterns to molecular mechanisms, and from bacteria to human cells.

Image left show ribosome (blue, orange) that synthesized protein chain (yellow) by translating the RNA message (red). Image right shows dynamic ribosome interactions.

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.

Work environment

AMOLF is a part of NWO-I and initiate and performs leading fundamental research on the physics of complex forms of matter, and to create new functional materials, in partnership with academia and industry. The institute is located at Amsterdam Science Park and currently employs about 140 researchers and 80 support employees. www.amolf.nl

Our group - We form a lively and close-knit research group of about 10 PhD students and postdocs, which work together in small teams on various projects in a highly supportive and social atmosphere that extends to the other research groups at the AMOLF institute, which is housed in a modern building in the east of Amsterdam. The Tans group at the AMOLF institute Amsterdam has been at the forefront of studying chaperone-guided protein folding using optical tweezers. This technique allows one to mechanically manipulate individual proteins, and hence follow the movements and folding steps as they fold. We have shown striking sequences of molecular events that underlie chaperone functions, which are invisible with other methods.

https://www.sandertanslab.nl
https://amolf.nl/research-groups/biophysics

Working conditions

• The working atmosphere at the institute is largely determined by young, enthusiastic, mostly foreign employees. Communication is informal and runs through short lines of communication.
• The position is intended as full-time (40 hours / week, 12 months / year) appointment in the service of the Netherlands Foundation of Scientific Research Institutes (NWO-I) for the duration of four years
• Funding is available to attend regularly international conferences.
• AMOLF assists any new foreign researcher with housing and visa applications and compensates their transport costs and furnishing expenses.

More information?
https://www.sandertanslab.nl

Application

You can respond to this vacancy online via the button below.

Please annex your:

• Resume;
• Motivation on why you want to join the group (max. 1 page).

It is important to us to know why you want to join our team. Hence, we will only consider your application if it contains your motivation letter.

Applications will be evaluated on a rolling basis and as soon as an excellent match is made, the position will be filled.

Online screening may be part of the selection.

Diversity code

AMOLF is highly committed to an inclusive and diverse work environment: we want to develop talent and creativity by bringing together people from different backgrounds and cultures. We recruit and select on the basis of competencies and talents. We strongly encourage anyone with the right qualifications to apply for the vacancy, regardless of age, gender, origin, sexual orientation or physical ability.

AMOLF has won the NNV Diversity Award 2022, which is awarded every two years by the Netherlands Physical Society for demonstrating the most successful implementation of equality, diversity and inclusion (EDI).