The Van 't Hoff Institute for Molecular Sciences (HIMS) is one of eight institutes of the Faculty of Science of the University of Amsterdam. (UvA). HIMS performs internationally recognized research in molecular sciences, both curiosity as well as application driven. This is partly done in cooperation with the chemical, energy, flavour & food, medical and high-tech industries.
Are you passionate about bioanalytical chemistry, and advanced separation technology, MS hyphenated methods, and are you looking for a PhD position? Would you like to work in a multidisciplinary team developing novel LC-MS characterization methods for the study of intact serum immunoglobulins?
Please apply to the UvA Amsterdam for a joint position between the the Analytical Chemistry Group of the UvA and the Center for Proteomics and Metabolomics at Leiden University Medical Center!
Current methodologies may capture overall structural changes in glycosylation but do not allow us to assess if and which combination of post-translational modification may be present (e.g. Ig bearing multiple glycosylations, or combination of glycosylation with other post-translational modifications). This is because of the current lack of technology for resolving the glycosylation complexity of intact Igs beyond standard singly glycosylated IgG1 species.
As a result, the study of glycoforms is mainly done at the glycan or glycopeptide level, missing crucial information on the localization and co-expression of glycoproteoforms. Additionally, the functional study of changes in (glyco)proteoforms requires cumbersome and error-prone glycoform purification strategies, as established affinity technologies cannot differentiate the properties of mixtures of glycoforms (and in general proteoforms).
State-of-the-art methods may capture overall structural changes in glycosylation but do not allow us to assess if and which combination of post-translational modification may be present (e.g. Ig bearing multiple glycosylations, or combination of glycosylation with other post-translational modifications). This is because of the current lack of technology for resolving the glycosylation complexity of intact Igs beyond standard singly glycosylated IgG1 species. As a result, the study of glycoforms is mainly done at the glycan or glycopeptide level, missing crucial information on the localization and co-expression of glycoproteoforms.
The goal of the HYPE-IMMUNe project is the development of methods, based on innovative separations coupled (HYPhEnated) to mass spectrometry to:
(i) structurally characterize Ig, resolving the proteoforms complexity of multiply glycosylated immunoglobulins, and
(ii) establishing glycoform-resolved, structure-function relationships. These advanced methods will be applied to studying antigen-specific B cell in vitro cultures aiming to describe the
(iii) regulation, and
(iv) effector functions of antibody glycoforms, opening new frontiers in elucidating their role in immunology.
This PhD position is embedded in the labs of both the the Analytical Chemistry Group at University of Amsterdam (UvA) and Center for Proteomics and Metabolomics at Leiden University Medical Center where you will be supervised by dr. Andrea Gargano and dr. Elena Dominguez Vega. Together with the team, you will present the obtained research results at national and international scientific conferences, and in relevant journals.
You are expected to: - Perform denaturing and non-denaturing LC-MS experiments on immunoglobulin serum samples;
- Work with low-flow separations;
- Explore advanced column formats including separation materials with tailored chemistry and morphologies for IgGs;
- Interpret mass spectrometry data from the analysis of intact Igs;
- Contribute to teaching and supervising activities (including supervision of MSc and BSc students);
- Collaborate within other international researchers;
- Publish scientific articles and present research results at international conferences and journals;
- Conduct research within the scope of the project leading to a dissertation and a PhD degree towards the end of the 4-year project.