PhD in biophysics: Single-cell Tracking in Organoids

Work Activities
Summary – In this project, you will use advanced 3D imaging and AI-driven cell tracking to reveal the remarkable self-organization of cells within intestinal organoids. Using a biophysics approach, you will study how stem cells move, grow, divide, and differentiate into specific functional cell types, and hence reveal how functional miniature organs are formed. Specifically, you will for the first time reveal how this spatio-temporal program is affected by key molecular signals from the immune system. You will work in a vibrant and supportive team of PhD students and postdocs with physics and biology backgrounds within the Tans and van Zon labs in the AMOLF institute in Amsterdam, and collaborate with leading groups in organoid biology.

Questions – According to the textbooks, organs like the intestine continuously regenerate new functional cells from stem cells. However, current methods like antibody staining and RNA sequencing are ill suited to address the inherent underlying spatio-temporal dynamics. These dynamics are arguably even more important to understand the interplay with immune signals, which are thought to affect the organ regeneration process. They are in turn central to the major and growing societal challenge of chronic inflammatory diseases such as intestinal bowel disease and Crohn’s disease. Many fascinating fundamental questions of broad relevance are therefore unresolved: Do signals like interleukins increase the stem cell pool or stimulate differentiation rates to boost renewal? Do they target specific cell types, or impact movement or position of cells? Do they cause cells within the intestine to signal to each other? Given the novelty of the AI-driven cell tracking approach, you will have a unique chance to address such questions first. In addition, the organoid field is currently undergoing a massive expansion yet generally lacks the physics-inspired dynamic methodology that you will help advance.

Approach – Central to the approach is 3D imaging with advanced confocal microscopy, and AI-driven cell tracking, but also organoid growth protocols, antibody staining, and genetic engineering of fluorescent markers, which you will do in collaboration with other PhD students and technical staff. This approach allows you to follow each cell, and hence analyze diverse features including lineage relations between cells of different type or within a specific spatial region, and how they correlate with the expression of key differentiation markers – and how these features are affected by molecular signals that are normally emitted by immune cells but that you add in controlled manner. These advances will allow you to push the boundaries of AI-enabled analysis of single-cell dynamics, which will be more generally relevant both to fundamental science and applications. This first has great potential to reveal a host of unexpected phenomena. More generally, you will develop new experimental schemes, perform cutting-edge experiments, analyze the complex spatio-temporal data, come up with new mechanistic models, and describe your findings in high-level scientific papers.

Qualifications
We are looking for outstanding experimental physicists, chemists, or biologists with demonstratable interest in quantitative biophysics questions, experience in programming and/or machine learning, handling of complex data, and who thrives 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
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.

Tans group: https://www.sandertanslab.nl

Van Zon group: https://amolf.nl/research-groups/quantitative-developmental-biology

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.
• AMOLF assists any new foreign PhD-student with housing and visa applications and compensates their transport costs and furnishing expenses.

More information?
For further information:
Prof. dr. ir. Sander Tans
tans@amolf.nl

Dr. Jeroen van Zon

J.v.Zon@amolf.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).

Commercial activities in response to this ad are not appreciated.

PhD-student: Tribochemical wear with relevance to nanolithography

Work Activities
Are you interested in simultaneously unraveling the fundamentals of wear and contributing to the solution of friction-related challenges in computer chip production?

At the Advanced Research Center for Nanolithography, we work with ASML on new processes to fabricate the electronic chips that power nearly every sector in the world. These chips are fabricated onto silicon wafers. During fabrication, nanometre scale relative displacements between the silicon wafer and the wafer positioner lead to unpredictable friction forces and wear which in turn cause in-plane deformations in the wafer, limiting the achievable feature size in chips.

While enormous progress has been made in fundamentally understanding wear, it remains striking that the most widely applied wear law (Archard’s law) is empirical and includes a proportionality constant that lacks a clear physical meaning but can vary over many orders of magnitude. Increasing evidence suggests that stiff and wear resistant materials, i.e. ceramics or diamond, undergo tribochemical, atomistic wear in which passivating species in the environment may play a crucial role. In this project, you will perform wear experiments on a recently developed instrument that enables customized wear experiments in controllable environment. The goal of the project is to provide insight into the industrially relevant wear behavior, leading to control over the wear behavior and its impact on positioning accuracy in nanolithography.

Qualifications

• Candidates have a MSc degree in physics, or a related subject.
• Candidates enjoy performing experiments and analysis to stepwise build a deeper, nanoscale understanding of complex physical mechanisms.
• Candidates enjoy communicating and explaining the results of their work.
• The ideal candidates have experience in using/developing instrumentation for mechanical/tribological testing.

Work environment
ARCNL performs fundamental research, focusing on the physics and chemistry involved in current and future key technologies in nanolithography, primarily for the semiconductor industry. While the academic setting and research style are geared towards establishing scientific excellence, the topics in ARCNL’s research program are intimately connected with the interests of the industrial partner ASML. The institute is located at Amsterdam Science Park and currently employs about 100 persons of which 65 are ambitious (young) researchers from all over the globe. www.arcnl.nl

Working conditions
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, with a starting salary of gross € 2,884 per month and a range of employment benefits. After successful completion of the PhD research a PhD degree will be granted at the University of Amsterdam. Several courses are offered, specially developed for PhD-students. ARCNL assists any new foreign PhD-student with housing and visa applications and compensates their transport costs and furnishing expenses.

We also offer:

• Opportunity to work with world-wide unique wear setups.
• Stimulating international institute in vibrant city.
• Opportunity to grow your experimental, analysis and communication skills through interaction with the other group members as well as academic and industrial collaborators.
• Supportive supervision and guidance.

The Advanced Research Center for Nanolithography (ARCNL) focuses on the fundamental physics and chemistry involved in current and future key technologies in nanolithography, primarily for the semiconductor industry. ARCNL is a public-private partnership between the Dutch Research Council (NWO), the University of Amsterdam (UvA), the VU University Amsterdam (VU), and associate partner the University of Groningen (RuG), and the semiconductor equipment manufacturer ASML. ARCNL is located at the Amsterdam Science Park, The Netherlands, and has a size of approximately 100 scientists and support staff. See also www.arcnl.nl

You will be embedded in the Contact Dynamics team at ARCNL, which investigates friction and wear in relation to positioning challenges in the semiconductor industry.

References:

1. L. Peng, C.-C. Hsu, C. Xiao, D. Bonn and B. Weber. Controlling Macroscopic Friction through Interfacial Siloxane Bonding. Phys. Rev. Lett. 131 226201 (2023).
2. F.-C. Hsia, S. Franklin, P. Audebert, A. M. Brouwer, D. Bonn and B. Weber. Rougher is more slippery: How adhesive friction decreases with increasing surface roughness due to the suppression of capillary adhesion. Phys. Rev. Res. 3, 043204 (2021).
3. F.-C. Hsia, F. M. Elam, D. Bonn, B. Weber and S. E. Franklin. Wear particle dynamics drive the difference between repeated and non-repeated reciprocated sliding. Tribol. Int. 142, 105983 (2020).
4. C. Leriche, C. Xiao, S. Franklin and B. Weber. From atomic attrition to mild wear at multi-asperity interfaces: The wear of hard Si3N4 repeatedly contacted against soft Si. Wear 528, 204975 (2023).

More information?
For further information about the position, please contact Bart Weber: b.weber@arcnl.nl .

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

Online screening may be part of the selection.

Diversity code
ARCNL 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.

Commercial activities in response to this ad are not appreciated.

Postdoc: Single-molecule microscopy of checkpoint therapeutic action on T cells

Work Activities
As postdoc member of the REPRESSIT consortium coordinated the Physics of Cellular Interactions group headed by Dr. Kristina Ganzinger, you will work on developing a new type of cancer therapeutic (checkpoint inhibitor) in a biophysical project right at the interface of biochemistry, biophysics and immunology in an EIC-funded European consortium.

Checkpoint blockage focuses on targeting inhibitory immune receptors with antibodies to prevent their activation by blocking ligand binding. This strategy has revolutionised immunotherapy helping millions of cancer patients with some spectacular results, providing a novel path to potentiate immune responses against tumour cells. Nevertheless, most patients fail to benefit from these antibody-based therapies highlighting critical pitfalls of the current checkpoint blockade approach: one of them is that blocking receptor-ligand interactions is insufficient to shut down inhibitory signalling completely.

By taking up this postdoc position, you will help changing the current ligand-centric “blockade” paradigm and focus on developing molecules that induce dephosphorylation of immune receptors (so-called RIPR molecules) to shut down their signalling entirely, in contrast to currently available therapeutics. Our approach termed REPRESSIT (Regulated phosphatase recruitment ends sustained signaling of inhibitory targets) can completely shut down even tonic inhibitory receptor signaling (Fernandes, R.A. et al. Immune receptor inhibition through enforced phosphatase recruitment. Nature 586, 779–784 (2020)). But how do this phosphase-recruiting molecule need to be designed to optimally shut down signalling?

In close collaboration with the Fernandes group (University of Oxford) and our other REPRESSIT partners, you will analyse the spatiotemporal dynamics of how different designs of RIPR molecules (Receptor Inhibition by Phosphatase Recruitment) modulate T cell receptor signalling both in live cells and model lipid bilayers with reconstituted receptor domains, using single-molecule fluorescence microscopy and single-particle tracking techniques. You will study both receptor organisation and receptor signalling (adaptor protein recruitment). From these experiments, we will understand the molecular basis of RIPR function and determine general biophysical design principles to further improve the potency of RIPR molecules. The performance of promising new RIPR designs we find will then be tested and compared against conventional antibodies preclinical models by our REPRESSIT partners. Ultimately, this project aims at developing and establishing proof-of-concept of the REPRESSIT platform for bringing these molecules to the clinic and patients.

Qualifications
You need to meet the requirements for a doctors-degree (PhD) and must have research experience in a non-Dutch academic environment. We are looking for a (bio)physicist who has already worked with single-molecule fluorescence techniques or an experimental (bio)chemist with strong experience in biophysical techniques and data analysis. Experience with single-molecule fluorescence microscopy or super-resolution microscopy, automated data analysis and coding (Python) is highly desired; knowledge of cell culture and/or protein biochemistry and/or model lipid systems would be an advantage. You should like the idea of working in a collaborative, ambitious and international environment. We ideally look for a candidate who can start this position in March 2025.

Work environment
AMOLF is 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 are a supportive and social research group of about 8 PhD students and postdocs, which work together in small teams on various projects from immunological signalling to signalling in synthetic cells. The collaborative and social atmosphere includes to the other research groups at the AMOLF institute at the Science Park in Amsterdam East. Our group has been making recent technical advances, including a new single-molecule tracking method based on DNA-PAINT that we recently developed (Nat Commun 2021, Nat Commun 2023), new in vitro assays (ACS Syn Biol 2021, ACS Omega 2024), and imaging approaches developed by our lab and others (JACS 2013, Nat Immun 2016, PNAS 2019), all to closely investigate the intricate molecular details of cellular signaling.

https://amolf.nl/research-groups/physics-of-cellular-interactions

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 2 years.
• Salary is in scale 10 (CAO-OI) which starts at 4.065 Euro’s gross per month, and a range of employment benefits.
• AMOLF assists any new foreign Postdoc with housing and visa applications and compensates their transport costs and furnishing expenses.

More information?
For further information about the position, please contact Kristina Ganzinger: k.ganzinger@amolf.nl or Raquel Martinez Gonzalez: R.MartinezGonzalez@amolf.nl.

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

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).

Commercial activities in response to this ad are not appreciated.

Postdoc: Surfaces and interfaces in plasma applications

Work Activities
Plasma discharges in gases create extremely challenging environments for surfaces. Protective coatings are often required to maintain the integrity of plasma-facing materials. However, plasma-induced etching of material and the diffusion of small elements such as hydrogen present challenges even for optimized materials and their coatings. In this project, you will perform in situ studies of the evolution of the surface and interface chemistry of materials exposed to radicals, ions, and full plasma. You will operate ultra-high vacuum tools for the preparation of surfaces and thin films, vacuum-based transfer to plasma exposure setups, and surface-sensitive in situ spectroscopy.

Qualifications
You have a PhD in Physics, Physical Chemistry, or a related field and experience in surface science and/or plasma-surface interactions.
You are motivated, independent, and have good project management skills.
Good verbal and written communication skills (in English) are required. Experience with ultra-high vacuum, photoelectron spectroscopy, scanning probe microscopy, and thin-film growth are considered an advantage for the project.

Work environment
ARCNL performs fundamental research, focusing on the physics and chemistry involved in current and future key technologies in nanolithography, primarily for the semiconductor industry. While the academic setting and research style are geared towards establishing scientific excellence, the topics in ARCNL’s research program are intimately connected with the interests of the industrial partner ASML. The institute is located at Amsterdam Science Park and currently employs about 100 persons of which 65 are ambitious (young) researchers from all over the globe. www.arcnl.nl

Working conditions
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 two years, with a salary in scale 10 (CAO-OI) and a range of employment benefits. ARCNL assists any new foreign Postdoc with housing and visa applications and compensates their transport costs and furnishing expenses.

More information?
For further information about the position, please contact Roland Bliem: r.bliem@arcnl.nl.

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

Online screening may be part of the selection.

Diversity code
ARCNL 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.

Commercial activities in response to this ad are not appreciated.

Postdoc: The real-time dynamics of single ribosomes

Work Activities
Summary - In this project, you will perform innovative (bio)physics experiments to elucidate the activity of individual ribosomes. The key methodologies are optical tweezers and single-molecule fluorescence. 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 that are specialized in RNA sequencing 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. Direct collaboration with our partners provides complementary genome-wide in-vivo data. 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?
For further information about the position, please contact

Prof. dr. ir. Sander Tans
tans@amolf.nl
https://www.sandertanslab.nl
Phone: +31-(0)20-754 7100

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).

Commercial activities in response to this ad are not appreciated.