PhD Position in Mass Spectrometry Instrumentation

A fully funded PhD position in the field of protein soft-landing instrumentation development at the Maastricht MultiModal Molecular Imaging (M4i) Institute, embedded in the Faculty of Health, Medicine and Life Sciences (FHML) at Maastricht University.

Job description
Macromolecular assemblies (MMAs), including protein complexes and viruses—are vital to many biological processes like signal transduction and cellular transport. Their higher-order molecular-structure defines their functions, making it crucial to study their molecular-structure with high-resolution and high-accuracy imaging methodologies. Ultimately this helps to gain novel insights into the fundamental processes of human health and disease.

Single-particle cryogenic-electron microscopy (cryo-EM) has emerged as a leading method for determining MMA structures at atomic resolutions. However, several challenges related to sample preparation, data collection and processing hinder further advancements in spatial resolution. This project focuses on improvements in the sample preparation of individual proteins for single particle Cryo-EM. A critical limitation in sample preparation is protein heterogeneity, which persists despite the use of pre-fractionation techniques, which are often insufficient to produce ultrapure samples for cryo-EM. The vitrification (e.g., plunge freezing) step is also challenging as particles can localize at the air-water interface, preventing random orientations necessary for 3D structural analysis. This issue combined with the difficulty of achieving uniform ice thickness necessitates extensive sample screening.

Recognizing these limitations, we will develop image-guided native mass spectrometry (nMS) as a sample preparatory tool for cryo-EM. nMS preserves non-covalent interactions within MMAs, maintaining native physiological conditions while transitioning to the gas phase. The mass and charge state selected native MMA particles can then be gently deposited (“soft-landing”) onto a cryo-cooled transmission EM (TEM) grid. This approach could mitigate the challenges of plunge freezing and reduce sample heterogeneity by leveraging the ultrahigh-resolution mass separation and selection capabilities of the MS, while maintaining the higher-order molecular-structure of MMAs.

This PhD project focusses on the design, development and construction of the soft-landing unit, encompassing its characterization; ion optics, mechanical, thermal, and electronic design; software development; construction; integration; step-by-step testing and optimization. Key components, such as the cryo-microcooler, water vapor deposition system, advanced ion optics, and imaging detectors, will be integrated progressively.

Along the way, you will develop and utilize a range of advanced skills, including imaging technologies and software, analytical and imaging methodologies, vacuum technology, biological sample preparation, and electrical and mechanical engineering. Furthermore, you are expected to present your work in scientific journals and at scientific conferences which will utilize skills such as technical writing, public speaking, and study of the current scientific literature base. You will also be able to gain experience teaching and mentoring bachelor and master students.

The successful PhD candidate will be supervised by Dr. Anjusha Mathew and Prof. Dr. Ron M. A. Heeren. This is a full-time, 4-year fully funded position at the M4i Institute at Maastricht University, Netherlands. The anticipated start date is early autumn 2025, but reasonable flexibility is available for the right candidate.

Requirements
Required:

• A master’s degree in Physics, Mechanical engineering, Instrumentation Engineering, Chemistry, Analytical Science and Technology, or a related subject;
• Proficiency in English (C1 or higher) and an open communicative attitude;
• Lab experience with physics or chemical instrumentation;
• Capacity to quickly acquire new knowledge and master new skills;
• Interest and ability in hands-on research activities;
• Ability to work independently and as a member of a research team;
• Problem solving skills and creativity;
• A desire and ability to share your research through oral and written communication.

Other experience / skills that would be helpful for the project:

• Vacuum technology instrumentation;
• Mass spectrometry;
• Ion beams and ion optics;
• Mechanical design and engineering;
• Electronics design and engineering;
• Transmission electron microscopy;
• Instrument control systems and software;
• Programming;
• Analytical techniques and methodologies;
• Biological sample preparation.

What we offer
As PhD Position in Mass Spectrometry Instrumentation at Faculty of Health, Medicine and Life Sciences, you will be employed by the most international university in the Netherlands, located in the beautiful city of Maastricht. In addition, we offer you:

• Good employment conditions. The position is graded in scale P according to UFO profile PhD, with corresponding salary based on experience ranging from €3059,00 and €3881,00 gross per month (based on a full-time employment of 38 hours per week). In addition to the monthly salary, an 8.0% holiday allowance and an 8.3% year-end bonus apply.
• An employment contract for a period of 12 months with a scope of 1,0 FTE. Upon a positive evaluation, an extension of 3 years will follow.
• At Maastricht University, the well-being of our employees is of utmost importance, we offer flexible working hours and the possibility to work partly from home if the nature of your position allows it. You will receive a monthly commuting and internet allowance for this. If you work full-time, you will be entitled to 29 vacation days and 4 additional public holidays per year, namely carnival Monday, carnival Tuesday, Good Friday, and Liberation Day. If you choose to accumulate compensation hours, an additional 12 days will be added. Furthermore, you can personalize your employment conditions through a collective labor agreement (CAO) choice model.
• As Maastricht University, we offer various other excellent secondary employment conditions. These include a good pension scheme with the ABP and the opportunity for UM employees to participate in company fitness and make use of the extensive sports facilities that we also offer to our students.
• Last but certainly not least, we provide the space and facilities for your personal and professional development. We facilitate this by offering a wide range of training programs and supporting various well-established initiatives such as 'acknowledge and appreciate'.

The terms of employment at Maastricht University are largely set out in the collective labor agreement of Dutch Universities. In addition, local provisions specific to UM apply. For more information, click here .

Maastricht University
Why work at Maastricht University?
At Maastricht University (UM), everything revolves around the future. The future of our students, as we work to equip them with a solid, broad-based foundation for the rest of their lives. And the future of society, as we seek solutions through our research to issues from all around the world. Our six faculties combined provide a comprehensive package of study programmes and research.

In our teaching, we use the Problem-Based Learning (PBL) method. Students work in small groups, looking for solutions to problems themselves. By discussing issues and working together to draw conclusions, formulate answers and present them to their peers, students develop essential skills for their fu