Currently, we have several open positions for Ph.D. and Postdoctoral researchers.
We are eager to meet with highly motivated and qualified applicants. We would like to fill these vacancies by the end of the summer. The project descriptions are listed below:
PhD Position 1: (PI Kelly Stecker, k.e.stecker@uu.nl)
PhD project in our Biomolecular Mass Spectrometry and Proteomics focused on characterizing the inter and intra-cellular signaling dynamics between immune and tumor cells with the aim of identifying novel regulators of immune-mediated tumor cell death and potential drug targets for cancer immunotherapy.
Description:
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.
For this position, 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.
Qualifications:
Experience with protein purification
Experience with mammalian cell culture including transfections and transductions
Experience with liquid chromatography platforms
Programming skills or R-experience is appreciated
Good spoken and written English language skills
PhD Position 2: (PI Maarten Altelaar, m.altelaar@uu.nl)
PhD project focused on characterizing intracellular signaling and protein-protein interactions at the cell-cell interface, using recent developments in phosphoproteomics and proximity labeling techniques in combination with high-resolution mass spectrometry.
Description:
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.
For this project we seek a highly motivated scientist with practical lab experience in biochemistry or molecular biology with 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.
Qualifications:
Experience handling protein samples
Experience with mammalian cell culture including transfections and transductions
Experience with liquid chromatography platforms
Experience with handling large data sets and statical analysis is appreciated
Programming skills or R-experience is appreciated
Good spoken and written English language skills
PhD position 3: (PI Karli Reiding, k.r.reiding @uu.nl)
Uncovering glycopeptide structural isomerism by mass spectrometry
Description:
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 multiply 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), 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.
Qualifications:
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
– Programming skills or R-experience are highly appreciated
Postdoctoral Researcher 1: (PI Maarten Altelaar, m.altelaar@uu.nl)
Description:
In recent years we have developed new proteomics methods ranging from improved separation and enrichment methodologies to new fragmentation techniques and targeted analysis of post-translation modifications (PTMs). These improvements enable us to decipher the complexity of the human proteome, consisting of dynamic proteinprotein interactions, PTMs, protein synthesis and degradation, protein complex assembly and disassembly, etc. To further advance the impact of our proteomics tools in the biological and clinical setting, this project will focus on increasing sensitivity of existing technologies to enable the analysis of single cell populations. Furthermore, we will aim for smooth integration of the experimental workflows and data analysis with other omics technologies such as genomics and metabolomics.
For this position, we seek a highly motivated biochemist or analytical chemist with proven expertise in mass spectrometry and proteomics. Having your own project, you will team-up with dedicated researchers combining expertise in biochemistry, analytical chemistry, mass spectrometry, and bioinformatics to further develop state-of-the-art proteomics methods that will answer pressing biological questions. As part of the Netherlands X-omics Initiative, you will interact and collaborate with national and international researchers to enable the efficient integration of proteomics data and workflows with other omics technologies and enable the translation of the integrated Xomics datasets into biologically relevant information.
Qualifications:
Experience operating high-end LC-MS systems
Experience with (phopsho)proteomics sample preparation protocols
Experience handling large data sets and statical analysis
Experience with mammalian cell culture is appreciated
Programming skills or R-experience is appreciated
Good spoken and written English language skills
Postdoctoral researcher 2: (PI Karli Reiding, k.r.reiding @uu.nl)
Proteomics applications to study the remodeling of neutrophils in cancer and in health
Description:
Neutrophils are highly abundant and important cells in the immune system. Yet, while most neutrophils are anti-pathogenic, a subset thereof is instead able to suppress T-cell activation. These so called myeloid-derived suppressor cells (MDSCs) often reside in the tumor microenvironment and prevent an effective immune response. Interestingly, it has been demonstrated that IgA is not only capable of directing neutrophils to attack tumor cells, but also that antibodies can significantly diminish the suppressive effects of MDSCs. However, the molecular basis of these effects remains unclear and needs to be further investigated.
The aim of the project is to develop and apply mass spectrometry (MS) technologies to characterize conventional and immunosuppressive neutrophils, to determine how these respond to immunoglobulin stimulation, and to find out how these differ within health and disease. Required techniques will include proteomics to determine protein abundances, as well as dedicated MS strategies to investigate post-translational modifications like glycosylation and phosphorylation.
Qualifications:
For this position, we seek a highly motivated biochemist or analytical chemist with experience in mass spectrometry, proteomics, and sample preparation methods. Having your own project, you will team-up with dedicated researchers combining expertise in biochemistry, analytical chemistry, mass spectrometry, and bioinformatics to further develop state-of-the-art proteomics methods that will answer pressing biological questions. Specifically, we request the following:
Experience with operating high-end LC-MS systems
Experience with proteomics sample preparation methods
Experience with glycoproteomics and/or phosphoproteomics is appreciated
Experience with handling large data sets and statistical analysis are appreciated
Programming skills or R-experience are appreciated
Good spoken and written English language skills
Recent illustrative work
- Kleinpenning F, et al. (2020) Fishing for newly synthesized proteins with phosphonatehandles. Nature Communications 11(1), 3244.
- van Gelder CAGH et al. (2020) Temporal Quantitative Proteomics of mGluR-induced Protein Translation and Phosphorylation in Neurons. Mol Cell Proteomics. 19(12):19521968.
- Schmidlin T, et al. (2019) High-Throughput Assessment of Kinome-wide Activation States. Cell Systems 9(4):366-374.
- Vredevoogd DW et al. (2019) Augmenting Immunotherapy Impact by Lowering Tumor TNF Cytotoxicity Threshold. Cell 178(3):585-599.e15.
- Čaval T, Heck AJR, Reiding KR. (2020) Meta-heterogeneity: Evaluating and Describing the Diversity in Glycosylation Between Sites on the Same Glycoprotein. Mol Cell Proteomics. 8(20), 100010.
More information and apply
https://www.uu.nl/en/research/biomolecular-mass-spectrometry-and-proteomics
- Location: Utrecht University, Utrecht, Netherlands
- Start date: After consultation, as soon as possible
- Apply with motivation letter, CV and 2 references
- Deadline for application: 1st July 2021
- For information or application: c.c.heuzer@uu.nl
