We are looking for three highly motivated PhD candidates to work in the area of cell signaling, glycoproteomics, and protein mass spectrometry on the following topics:

1) Cell signaling and immune-mediated tumor cell death, supervised by Dr. Kelly Stecker:

Stimulating the immune system to kill cancer cells through immune checkpoint blockade (ICB) therapy has been a recent breakthrough in cancer treatment, however, less than 30% of melanoma patients experience a durable response ICB therapy due to resistance mechanisms. To tackle resistance to ICB therapy, we need to define how cytotoxic immune cells engage with tumor cells and successfully initiate killing. To this end, this project will aim to map protein signaling networks between immune cells and tumor cell using mass spectrometry (MS) based (phospho)proteomics. As part of this work, this project will focus on isolating protein complexes and applying novel MS-based methods to identify protein-protein interactions and protein post-translational modifications. Ultimately our aim is to define new drug targets that can work in combination with existing ICB therapy to improve tumor clearance by the immune system.

Project-specific requirements: We seek a highly motivated scientist with practical lab experience in molecular biology and biochemistry, specifically in the area of protein purification, analytical chemistry, and molecular cloning. You will be responsible for your own project as well as working with a team to manage state-of-the-art mass spectrometry instrumentation in a diverse work environment. Therefore, strong initiative, time management, and communication skills in English are required to be successful in this position. For detailed questions on this topic and the PhD itself, feel free to contact k.e.stecker@uu.nl. 

2) Capturing signaling dynamics at the cell-cell interface, supervised by Prof. Maarten Altelaar:

Natural killer cells are part of the innate immune system and provide a rapid response to viruses and other intracellular pathogens. NK cells are unique in the sense that they do not need antibodies of MHC to recognize and kill ‘stressed’ cells. Recently, it was shown NK cells are also able to kill tumor cells and thus became of great interest as immunotherapy approach, which further increased with the discovery that NK cells have memory-like properties that can be passed on to next generations. The understanding of this memory-like effect in NK cells and its role in the interaction with tumor cells is crucial to guide future attempts to bring NK cytotoxicity to the clinic. In this project, we will use high-resolution proteomics in combination with proximity labeling methods to resolve protein-protein interactions involved in NK: tumor cell interactions and use targeted MS to monitor the dynamics of the signaling circuits involved in regulation NK memory. 

Project-specific requirements: For this project, we seek a highly motivated scientist with practical lab experience in biochemistry or molecular biology with an affinity for analytical chemistry and molecular cloning. You will be responsible for your own project as well as working with a team to manage state-of-the-art mass spectrometry instrumentation in a diverse work environment. Therefore, strong initiative, time management, and communication skills in English are required to be successful in this position. For detailed questions on this topic and the PhD itself, feel free to contact m.altelaar@uu.nl. 

3) Uncovering glycopeptide structural isomerism by mass spectrometry, supervised by Dr. Karli Reiding:

Glycosylation, the attachment of oligosaccharides to amino acid side chains, is an important co- and post-translational protein modification that has critical roles in, e.g., protein function, receptor affinity, and pathogen-host interactions. The glycans themselves may differ in composition and structure and minor changes can have large consequences. However, many important glycan characteristics are not simple monosaccharide substitutions but are based on isomeric properties like linkage and branching. Mass spectrometry (MS) is a powerful technique for glycosylation analysis: starting with a glycopeptide, MS can sequence both the glycan and the peptide, thereby providing site-specific information for multiple glycosylated proteins. Peptide sequencing also allows MS to handle complex glycoprotein mixtures like blood plasma, as glycosylation and changes therein can be assigned to specific proteins and glycosylation sites. However, as mass alone does not distinguish isomerism (equal mass), the assignment of this important glycosylation characteristic remains a substantial analytical challenge.

The aim of the project is to develop MS methodology to distinguish glycopeptide isomers, to ultimately apply this within (glyco)proteomics approaches. This development is expected to open up considerable avenues for biomarker research, patient stratification, and pharmaceutical antibody development/quality control, as structural ambiguity of glycosylation will be replaced by structural determination.

Project-specific requirements: For this position, we seek a highly motivated scientist with practical lab experience in biochemistry, analytical chemistry, and data analysis. You will be responsible for your own project as well as working with a team to manage state-of-the-art mass spectrometry instrumentation in a diverse work environment. Therefore, strong initiative, time management, and communication skills in English are required to be successful in this position. Specifically, we request the following: experience with mass spectrometry and liquid chromatography, experience with biochemistry techniques, good spoken and written English language skills, and programming skills or R-experience are highly appreciated.

For detailed questions on this topic and the PhD itself, feel free to contact k.r.reiding@uu.nl. 

We are looking for candidates with:

• a Master’s degree in the field of analytical or biochemistry, molecular biology, or relevant fields;
• lab experience with molecular biology and analytical chemistry techniques;  
• very strong written and oral communication skills in English;
• experience with handling large datasets and basic programming skills is a plus.

• a full-time position for four years;
• a full-time gross salary that starts at €2,395 and increases to €3,061 per month during the appointment (scale P of the Collective Labour Agreement Dutch Universities (cao));
• benefits including 8% holiday bonus and 8.3% end-of-year bonus;
• a pension scheme, partially paid parental leave, and flexible employment conditions based on the Collective Labour Agreement Dutch Universities.

In addition to the employment conditions laid down in the cao for Dutch Universities, Utrecht University has a number of its own arrangements. For example, there are agreements on professional development, leave arrangements, and sports. We also give you the opportunity to expand your terms of employment via the Employment Conditions Selection Model. This is how we like to encourage you to continue to grow.

More information about working at the Faculty of Science can be found here.

The three positions correspond to three distinct projects offered by Dr. Kelly Stecker, Prof. Maarten Altelaar and Dr. Karli Reiding.  You will be part of the larger Biomolecular Mass Spectrometry and Proteomics group. The group focuses on the use of mass spectrometry to understand the inner workings of cells. Mass spectrometry enables the characterization of molecules that are present in cells and thereby allows the identification and characterization of proteins and other biomolecules that work together and are involved in cellular processes and in disease. The group houses an excellent array of state-of-the-art mass spectrometers, combined with extensive protein and peptide separation methods, cell culture and molecular biology labs, and bioinformatics infrastructure. The group has world-renown expertise in the analysis of intact (native) proteins, proteomes, post-translational modifications, protein-protein interactions, and cellular signaling by mass spectrometry. Therefore, dedicated mass spectrometers and LC methods have been and are developed allowing the analysis of the structure and function of protein machineries.

At the Faculty of Science, there are six departments to make a fundamental connection with: Biology, Chemistry, Information and Computing Sciences, Mathematics, Pharmaceutical Sciences, and Physics. Each of these is made up of distinct institutes that work together to focus on answering some of humanity’s most pressing problems. More fundamental still are the individual research groups – the building blocks of our ambitious scientific projects.

Utrecht University is a friendly and ambitious university at the heart of an ancient city. We love to welcome new scientists to our city – a thriving cultural hub that is consistently rated as one of the world’s happiest cities. We are renowned for our innovative interdisciplinary research and our emphasis on inspirational research and excellent education. We are equally well-known for our familiar atmosphere and the can-do attitude of our people. This fundamental connection attracts Researchers, Professors and PhD candidates from all over the globe, making both the university and the Faculty of Science a vibrant international and wonderfully diverse community.