PhD student in mass spectrometry of aggregating proteins

For the position of PhD student in mass spectrometry of aggregating proteins, you will develop mass spectrometry and biochemical methods to investigate protein aggregation in neurodegeneration at VectorY Therapeutics and VU Amsterdam.

Are you driven by analytical chemistry of proteins? Do you want to develop mass spectrometry and biochemical methods to investigate protein aggregation in neurodegeneration?

Your function

Neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are strongly associated with pathological aggregation of the protein TDP-43. Increasing evidence indicates that early-stage oligomeric intermediates are key drivers of toxicity. However, these transient, low-abundant and heterogeneous species are extremely challenging to detect and characterize with conventional techniques.

In this project, you will develop and apply advanced native ion mobility mass spectrometry (IM‑MS) to study early aggregation intermediates of TDP‑43. In parallel, you will work with complementary biochemical, cellular, and protein‑based methods to build a comprehensive molecular understanding of how TDP‑43 aggregates and how therapeutic antibodies can modulate this process. These combined approaches allow you to characterize disease‑relevant TDP‑43 variants, including post‑translationally modified forms, and to evaluate how different interventions affect their aggregation behavior.

During your PhD, your work will involve native and structural mass spectrometry, complementary analytical chemistry methods, and protein biochemistry. You will produce TDP‑43 variants from different cellular systems and ensure their stability during sample processing. You will develop and apply native MS workflows to probe early stages of aggregation pathways, complemented by cellular and imaging approaches to study later stages of aggregation. This includes examining how VectorY’s antibodies interact with oligomeric species and how these interactions shape aggregation outcomes across different biological models.

Analytical chemistry and protein biochemistry both play important roles in this project. Experience with mass spectrometry (ideally native MS, IM‑MS, structural MS) and protein biochemistry techniques (such as protein purification, cell culture, immunoprecipitation, chromatography, or cellular imaging) are beneficial, and you will have the opportunity to further develop your expertise across these complementary areas. You will be embedded across the VU Amsterdam (Division of BioAnalytical Chemistry) and VectorY, with access to advanced ion mobility mass spectrometry instrumentation, state-of-the-art protein expression platforms, and cellular assay facilities.

The PhD position is part of the Health~Holland Industrial PhD call TARGET-43 and is embedded both at VectorY and VU Amsterdam. At VU Amsterdam, you are part of the Division of BioAnalytical Chemistry and you will join the MS-LaserLab, where you will be supervised by Prof. dr. Anouk Rijs and dr. Melissa Bärenfänger. At VectorY, you will be embedded in the Research Department and supervised by dr. Rob Haselberg and dr. Wouter Pos.

Your duties

• Develop and optimize native ion mobility mass spectrometry workflows to detect and structurally characterize early‑stage TDP‑43 oligomers.
• Apply IM‑MS and complementary proteomics approaches to study post‑translationally modified variants and define how these modifications influence oligomer formation.
• Produce and purify recombinant TDP‑43 variants from multiple cellular systems and maintain sample integrity for biophysical and cellular studies.
• Perform cellular and biochemical assays, including imaging‑based aggregation analysis, to evaluate late‑stage aggregation and therapeutic antibody effects.
• Contribute to teaching and supervising activities (including supervision of BSc and MSc students) at the Division of BioAnalytical Chemistry (VU Amsterdam).
• Collaborate closely with academic and industrial partners.
• Present research results at (inter)national conferences and publish in peer-reviewed journals.
• Conduct research within the scope of the project leading to a dissertation and a PhD degree (4-year project).

Your profile

• MSc degree in Analytical Chemistry, Bioanalytical Sciences, Molecular Life Sciences, or a closely related discipline.
• Strong proficiency in analytical mass spectrometry (e.g., native MS, ion mobility MS, structural MS) and/or protein biochemistry techniques (e.g., recombinant expression, purification, immunoprecipitation, chromatography), with motivation and skills to develop expertise across both analytical and biochemical approaches.
• Motivated interest in protein aggregation mechanisms, neurodegeneration, post‑translational modifications, and/or therapeutic antibody interactions.
• Strong affinity for method development, instrumentation troubleshooting, and interdisciplinary research combining analytical and biological systems.
• Excellent oral and written communication skills in English.
• Ability to work independently and collaboratively in a multidisciplinary academia-industry environment.

What do we offer?

You will be appointed at VectorY Therapeutics B.V. and enrolled as a PhD student at VU Amsterdam.

About us

About the division of BioAnalytical Chemistry (MS-LaserLab)

The Division of BioAnalytical Chemistry (BAC), within the Department of Chemistry and Pharmaceutical Sciences and AIMMS, develops and applies cutting-edge multidimensional analytical chemistry to unravel molecular mechanisms in biological and chemical processes. BAC combines internationally recognized research with research-driven education of BSc, MSc, and PhD students, offering courses across Chemistry (joint degree with UvA), Pharmaceutical Sciences, Drug Discovery Sciences, and Medical Natural Sciences. For research and teaching, BAC strongly collaborates with the analytical-chemistry group of the University of Amsterdam (UvA) in the Center for Analytical Sciences Amsterdam (CASA). Within the MS-LaserLab team, we develop and apply native, ion mobility mass spectrometry integrated with molecular spectroscopy and selective separations to elucidate molecular structure, interactions, and dynamics in key biological processes. Our central goal is to define how early oligomers and distinct proteoforms drive protein aggregation in neurodegeneration, guiding precise, mechanism-based therapeutic strategies.

About VectorY Therapeutics

VectorY Therapeutics B.V. is an innovative biotech company that is pioneering vectorized antibody therapies to reverse the course of neurodegenerative diseases. VectorY combines the therapeutic potential of antibodies with AAV-based delivery to develop long-lasting therapeutic solutions for neurodegenerative diseases of high unmet medical need. Founded in August 2020 and based in the Amsterdam Science Park, VectorY is a fully integrated precision medicines company focused on the development of innovative vectorized antibody therapies for the treatment of neurodegenerative diseases such as ALS, FTD, and Huntington’s disease.