Our laboratory, a world-leader in the field of proteomics, emphasizes its work on the development of advanced mass spectrometry-based methods to address questions in proteomics and structural biology. The laboratory houses an excellent infrastructure, including a dozen state-of-the-art mass spectrometers, advanced separation technologies, bioinformatics, and laboratories for cell culture, biochemistry and molecular biology. The research group Biomolecular Mass Spectrometry and Proteomics is vibrant and houses over 15 nationalities - Utrecht is a great place to be!

For all three positions, the work is embedded in the European Proteomics program Epic-XS and participation in international meetings for this consortium is expected. The aim is to implement the developed technologies into the access sites, promoting collaborations.

Position 1



The Scheltema laboratory focusses on the development and application of cross-linking mass spectrometry (XL-MS) to study protein-protein interactions. This technology utilizes small and agile reagents that covalently connect amino acids in close proximity. After proteolytic digestion, mass spectrometry can identify the connected amino acids. From these identifications distances constraints are derived that can be placed in in protein 3D structures, either known or directly predicted using this information. The structural details, at a resolution in the range of a few nanometers, allow resolving interaction interfaces between proteins. This can be done either in-vitro or in-situ in a close-to-native environment, making XL-MS an incredibly powerful approach for cell and structural biology. For this position, you will join a team of dedicated researchers combining expertise in bioinformatics, biochemistry, mass spectrometry, and structural modeling on a variety of systems and organisms to answer cutting-edge questions in biological sciences. You are expected to apply size-exclusion chromatography and sucrose gradient ultracentrifugation to purify interesting protein assemblies, perform the cross-linking and mass spectrometry assays, perform data analysis and integrate the data into structural models. As part of the European Proteomics program Epic-XS you will interact and collaborate with international researchers and develop new methods for cross-linking mass spectrometry.

Recent illustrative work

1. P Albanese, S Tamara, G Saracco, C Pagliano, RA Scheltema (2020) How paired PSII-LHCII supercomplexes mediate the stacking of plant thylakoid membranes unveiled by integrative structural mass-spectrometry Nature Communications 11, 1361
2. O Klykov, C van der Zwaan, AJR Heck, AB Meijer, RA Scheltema (2020) Missing regions within the molecular architecture of human fibrin clots structurally resolved by XL-MS and integrative structural modeling Proceedings of the National Academy of Sciences 17 (4), 1976-1987
3. B Steigenberger, RJ Pieters, AJR Heck, RA Scheltema (2019) PhoX: An IMAC-Enrichable Cross-Linking Reagent ACS Central Science 5 (9), 1514-1522

Position 2



Translational proteomics has made significant progress in recent years with improved protocols for the analysis of clinically important samples such as patient biopsy tissue material and different types of liquid biopsies. The analysis of patient tissue material allows the investigation of the disease state and the treatment response directly in the native in vivo environment and thereby provides valuable molecular disease information with high translational capacity. To make translational proteomics a main technology in clinical settings, several challenges need to be addressed. Here, we will focus on tissue biopsies, as the life in vivo setting, and extracellular vesicles (EVs), which potentially contain biomarkers for diagnosis and prognosis of disease conditions. Proteomics approaches will consist of high-end shotgun proteomics and targeted proteomics (e.g. DIA and SRM). For this position, we seek a highly motivated Biochemist or Analytical Chemist with proven expertise in mass spectrometry and clinical proteomics. You will join a team of dedicated researchers combining expertise in biochemistry, analytical chemistry, mass spectrometry and bioinformatics on a variety of systems to answer pressing clinical questions. As part of the European Proteomics programme Epic-XS you will interact and collaborate with international researchers and develop new methods to translate proteomics results in clinically relevant information.

Recent illustrative work

1. Schmidlin T, Debets DO, van Gelder CAGH, Stecker KE, Rontogianni S, van den Eshof BL, Kemper K, Lips EH, van den Biggelaar M, Peeper DS, Heck AJR, Altelaar M. (2019) High-Throughput Assessment of Kinome-wide Activation States. Cell Systems 9(4):366-374.
2. Rontogianni S, Synadaki E, Li B, Liefaard MC, Lips EH, Wesseling J, Wu W, Altelaar M. (2019) Proteomic profiling of extracellular vesicles allows for human breast cancer subtyping. Communications Biology 2:325.
3. Zagorac I, et al. (2018) In vivo phosphoproteomics reveals kinase activity profiles that predict treatment outcome in triple-negative breast cancer. Nature Communications 9(1), 3501.

Position 3



In recent years we have been developing new mass analyzers and new fragmentation techniques targeted towards the direct analysis of intact proteins and protein complexes by native and top-down proteomics. Such analyses on the one hand allow us to directly probe stoichiometries and structures of large protein assemblies, like viruses and ribosome particles, on the other hand they make it possible to identify and quantify distinct proteoforms of proteins highly modified by post-translational modifications such as phoshoproteins and (plasma) glycoproteins. Introducing charge detection single particle mass spectrometry and ECD and UVPD fragmentation on Orbitrap platforms has provided us with an unprecedented toolbox to discover so far little explored relevant parts of the proteome. For this position, we seek a highly motivated Biochemist or Analytical Chemist with proven expertise in biomolecular mass spectrometry. Having your own project, you will join a team of dedicated researchers combining expertise in bioinformatics, engineering and instrument development, biochemistry, analytical chemistry, and structural biology, and work on a variety of systems and organisms to answer cutting-edge questions in biological sciences. As part of the European Proteomics program Epic-XS you will interact and collaborate with international researchers and develop new methods for native mass spectrometry and top-down proteomics.

Recent illustrative work

1. TP Wörner, J Snijder, A Bennett, M Agbandje-McKenna, AA Makarov, AJR Heck (2020) Resolving heterogeneous macromolecular assemblies by Orbitrap-based single-particle charge detection mass spectrometry Nature Methods 17(4), 395-398.
2. JF Greisch, S Tamara, RA Scheltema, HWR Maxwell, RD Fagerlund, PC Fineran, S Tetter, D Hilvert, AJR Heck (2019) Expanding the mass range for UVPD-based native top-down mass spectrometry Chemical Science 10(30), 7163-7171
3. M van de Waterbeemd, KL Fort, D Boll, M Reinhardt-Szyba, A Routh, AA Makarov, AJR Heck (2017) High-fidelity mass analysis unveils heterogeneity in intact ribosomal particles Nature Methods 14(3), 283-286.

To excel in these roles, you have:

• experience running mass spectrometry experiments;
• experience in protein structural modelling and docking (position 1);
• laboratory/sample preparation experience;
• performed data analysis in software like MaxQuant, Proteome Discoverer, Byonic, etc.

• integration within a highly motivated, well equipped lab;
• a full-time position for 2 years;
• a full-time gross salary ranging from €2,709 to €4,274 (scale 10 according to the Collective Labour Agreement Dutch Universities);
• the salary is supplemented with a holiday allowance of 8% and an end-of-year bonus of 8.3% per year;
• a pension scheme, partially paid parental leave, and flexible employment conditions based on the Collective Labour Agreement Dutch Universities (cao). 

The positions are part of a European consortium providing high quality access to non-proteomics laboratories.

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 yourself 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.

Our laboratory, a world-leader in the field of proteomics, emphasizes its work on the development of advanced mass spectrometry-based methods to address questions in proteomics and structural biology. The laboratory houses an excellent infrastructure, including a dozen state-of-the-art mass spectrometers, advanced separation technologies, bioinformatics, and laboratories for cell culture, biochemistry and molecular biology. The research group is vibrant and houses over 15 nationalities - Utrecht is a great place to be!

At the Faculty of Science there are 6 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 which 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.