Publication date:

May 4th 2020

PhD position in GPCR signalling

G Protein coupled receptors (GPCRs) are promising targets for treatment of cancer, as well as immune and inflammatory diseases. Next to small molecules, antibody therapeutics are recently found to modulate GPCR function with better specificity and longer lasting effects.

In this project, you will use combined techniques in mass spectrometry and cancer biology to study the mechanisms of novel antibody/nanobody therapeutics and bispecifics targeting GPCRs and GPCR oligomerisation. In this inter-disciplinary project bridging mass spectrometry, cell biology, and antibody/nanobody engineering, you will also become part of an extended research network collectively aimed at revealing the intricacies of GPCR signalling and rational perturbations for therapy. This ‘MAGNETIC’ consortium is funded by the NWO-ENW-PPS scheme, to develop the next-generation of GPCR-targeting pharmaceuticals. Applicants with prior knowledge in cell signalling are preferred; prior hands-on MS experience is not critical at the start.

Publication date:

April 21st 2020

3 PostDoc positions on Epic-XS projects

Are you interested in developing a cutting-edge research program focused on developing and applying bioanalytical and biochemical approaches to investigate biological and disease processes?

General

Within the European consortium Epic-XS (https://epic-xs.eu) three different 2-year post-doctoral positions are available at Utrecht University, placed within the Heck-lab (https://hecklab.com), Altelaar-lab (https://altelaarlab.com/), and the Scheltema-lab (https://scheltemalab.com). The research emphasizes 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!

For all 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: Mass spectrometry driven structural investigations (https://scheltemalab.com)

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: Clinical proteomics (https://altelaarlab.com/)

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 program 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: Native and top-down proteomics (https://hecklab.com)

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 they make it possibly 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.

Publication date:

Jan 28th 2020

Assistant Professor Analytical and Biological Mass Spectrometry (Tenure Track) (1.0 FTE)

Are you interested in developing a cutting-edge research program focused on developing and applying bioanalytical and biochemical approaches to investigate biological and disease processes?

Job description

The Biomolecular Mass Spectrometry and Proteomics of Utrecht University is seeking outstanding applicants for a tenure-track faculty position to broaden its research focus. We invite applications from researchers who will build an independent research line combining technology and/or methodology development with a clear defined biological focus. We expect this focus to fit with the research lines in the research group, e.g. examining the importance of post-translational modifications such as lipidation, phosphorylation or glycosylation, and its regulating role in immunology, neurobiology, and tumor biology. The methodological developments from the applicant should be complementary to current efforts in the group, and in particular candidates seeking to develop novel methods for sample preparation and analysis, e.g. nanopore based protein sequencing or single cell proteomics are encouraged to apply.
You will be expected to actively seek funding for new research projects through personal, national, European and other international grant opportunities and supervise research projects of post-doctoral researchers, PhD candidates and MSc students. In addition, you have the ambition to actively participate in teaching activities at both the BSc and MSc level.

Requirements

Candidates should have a PhD degree, at least two years of postdoctoral research experience and a strong track record in research accomplishments. You have the vision and ambition to build an independent research line, and the ability to obtain research funding. You have affinity and enthusiasm for academic teaching, and the potential to coach and to guide PhD candidates and students. You have obtained or are willing to obtain a Basic Teaching Qualification. You are able to demonstrate excellent English language proficiency. We require a qualification English at C1 level (CEFR or comparable to level 3 of the lecturer Assessment Grid) or you are prepared to obtain this level by training. Our department is committed to affirmative action, equal opportunity and the diversity of its workforce, and we strongly welcome women to apply.

Conditions of employment

We offer a position (1.0 FTE) for the duration of five years in an international working environment. In case of a good performance, an indefinite employment is one of the possibilities. The gross salary – depending on previous qualifications and experience  – ranges between €3,637 and €5,656 (scale 11/12 according to the Collective Labour Agreement Dutch Universities) per month for a full-time employment.

The candidate is offered a tenure track position of 5 years, which will be subject to a mid-term evaluation after approximately 2,5 years and an end-term evaluation. When evaluations are positive the position becomes permanent after 5 years. The appointment is at the level of assistant professor (“universitair docent”).

Salaries are supplemented with a holiday bonus of 8% and a year-end bonus of 8.3% per year. In addition, Utrecht University offers excellent secondary conditions, including an attractive retirement scheme, (partly paid) parental leave and flexible employment conditions (multiple choice model). More information about working at Utrecht University can be found here.

Enjoy a great work-life balance in a wonderful city. Utrecht is an attractive city located in the heart of the Netherlands, one of the world’s most open and connected countries. Utrecht University reflects this philosophy by offering a flexible work-life balance that prioritizes your well-being in an understanding and supportive, international environment.

Employer

A better future for everyone. This ambition motivates our scientists in executing their leading research and inspiring teaching. At Utrecht University, the various disciplines collaborate intensively towards major societal themes. Our focus is on Dynamics of Youth, Institutions for Open Societies, Life Sciences and Sustainability.

The Faculty of Science consists of six departments: Biology, Pharmaceutical Sciences, Information and Computing Sciences, Physics and Astronomy, Chemistry and Mathematics. The Faculty is home to 6,000 students and nearly 1,500 staff and is internationally renowned for the quality of its research. The Faculty’s academic programmes reflect developments in today’s society.

Utrecht University has great ambitions for its teaching quality and study success rates. This also applies to its clear research profiles which are centred around four themes: Sustainability, Life Sciences, Youth & Identity, and Institutions. Utrecht University plays a prominent role in our society and contributes to finding the answers to topical and future societal issues.

The Biomolecular Mass Spectrometry and Proteomics group develops and implements innovative mass spectrometric methods for the more efficient and detailed characterization of peptides, proteins and metabolites in relation to their biological function. A large emphasis is on the structural characterization of proteins and their post-translational modifications as well as the investigation of protein complexes and protein interactions. In short, the group applies biomolecular mass spectrometry to problems in proteomics, metabolomics, cell biology and in structural biology. This means research covers many facets from cellular biology. We are interested in answering questions related to understanding as well as influencing proteins and their interactions, and how they function in regulating development, infection, but also immunological- and neurological disorders and cancer. Our research program is part of the Utrecht Institute for Pharmaceutical Sciences (UIPS) and the Bijvoet Center for Biomolecular Research.

Additional information

For more information about this position, please contact:

Prof A.J.R. Heck (Chair of division Biomolecular Mass Spectrometry and Proteomics), via a.j.r.heck@nulluu.nlor (030) 253 67 97.

Publication date:

Oct 21st 2019

Two Post-doctoral and two PhD Vacancies in Heck-lab

 In the Heck-lab at Utrecht University (www.hecklab.com) a variety of exciting research projects seek motivated researchers to tackle them. The research emphasis is on the development of advanced mass spectrometry-based methods to address questions in proteomics and structural biology. The Heck-lab houses and 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 quite vibrant with over 15 nationalities being present. Utrecht is a great place to be.

Postdoc positions (minimum of 2 years)

1. Viruses and other macromolecular assemblies studied by Biomolecular Mass Spectrometry

You will focus on the further optimization of native mass spectrometry and top-down proteomics for the analysis of macromolecular complexes, notably viruses, with the aim to generate even higher sensitivity and resolving power, contributing to the further development of single particle charge detection mass spectrometry. As some viruses are used for gene-delivery this project will partly be in collaboration with industry. You have ideally a background in biophysical and/or analytical chemistry.

2. Monitoring and Visualizing Protein Societal Behavior in the Cell; an Integrative Approach

The main goal is to develop an integrated approach to characterize proteins and their assemblies in the thermophiles Pyrococcus furiosusand Thermus thermophilus. Both these organisms are evolutionary fascinating and perfectly amendable as model systems in integrated structural biology. You will be part of a consortium that will use a combination of analytical and biophysical techniques with integrative structural modelling strategies. You will focus on native MS, top-down proteomics and crosslinking mass spectrometry (XL-MS) to uncover protein complexes in an unbiased fashion, ideally in their native state and ultimately in situ. You have ideally a background in biophysical and/or analytical chemistry.