Phd Student: The Single-molecule Biophysics of Ribsomes and Phase Separation

**Work Activities**:
**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 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. You meet the requirements for an MSc-degree to ensure eligibility for a Dutch PhD examination.

**Work environment**:
**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.

**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
- The starting salary is 2.781 Euro’s gross per month and a range of employment benefits.
- After successful completion of the PhD research a PhD degree will be granted at Delft University of Technology.
- Several courses are offered, specially developed for PhD-students.
- Funding is available to attend regularly international conferences.

**More information?**:
**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).

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 has won the NNV Diversity Award 2022, which