PhD Position Understanding How Genetic Changes Affect Brain Cells Using Single-Cell and Spatia

Join us to decode how genetic variation reprograms brain cells and disrupts their communication using AI

We are looking for a PhD student to work at the intersection of machine learning, single-cell genomics, and neurogenetics. Your project will focus on developing new methods to understand how genetic variants affect not only individual brain cells but also change the way cells interact and communicate - insights that are essential for understanding the cellular origins of brain disorders.

Despite major progress in genetics research, we still don't know how genetic risk factors for brain disorders like schizophrenia, alzheimer, and depression disrupt brain function. Genetic discoveries point to thousands of disease-associated SNPs, but most of them act in subtle and cell type-specific ways, and their downstream biological effects remain poorly understood.

This project tackles this fundamental gap - by building computational models that simulate what goes wrong in the brain, one cell (and one cell-cell interaction) at a time.

You will work with large-scale single-cell and spatial transcriptomics data to develop and apply single-cell foundation models - generative machine learning models that represent the structure and variation of cell states. These models act as virtual cells simulating how perturbing the expression of genes altered by genetic variants affects the cell's identity, behavior, and trajectory. You will extend these models to understand how genetic risk factors alter cell-cell communication networks. Spatial transcriptomics datasets will be used to anchor these models in real tissue context, revealing how spatially organized cell communities rewire under genetic perturbation.

• Use and improve single-cell foundation models to predict SNP-driven shifts in cell state and cell fate.
• Integrate spatial transcriptomics data to anchor these predictions in tissue context.
• Develop machine learning methods (e.g. Graph neural networks, variational or diffusion models) to model cell-cell communication dynamics under genetic perturbation.
• Investigate how local interactions between perturbed and unperturbed cells reshape signaling networks and tissue states.
• Closely collobarate with neuroscientists in the BRAINSCAPES consortium to link model predictions to experimental and clinical relevance.

• Shape next-generation models for understanding brain disease mechanisms.
• Work in a collaborative, interdisciplinary, and dynamic environment with leading experts in machine learning, computational biology, and neurogenomics.
• Access cutting-edge datasets, infrastructure, and computational and experimental facilities.
• Receive support for professional development and participation in international conferences.

• A Master's degree in computational biology, machine learning, bioinformatics, AI, or a related field.
• Strong background in machine learning and data analysis.
• Interest in single-cell omics, spatial data, or systems neuroscience.
• Intellectual curiosity, independence, and motivation to tackle open-ended problems with real-world impact.
• Strong analytical thinking and problem-solving skills.
• A passion for using AI to answer fundamental questions in biology and medicine.
• Ability to work independently and as part of a multidisciplinary team.
• Strong interpersonal communication and collaboration abilities
• Strong communication skills and proficiency in English.

Delft University of Technology is built on strong foundations. As creators of the world-famous Dutch waterworks and pioneers in biotech, TU Delft is a top international university combining science, engineering and design. It delivers world class results in education, research and innovation to address challenges in the areas of energy, climate, mobility, health and digital society. For generations, our engineers have proven to be entrepreneurial problem-solvers, both in business and in a social context.

At TU Delft we embrace diversity as one of our core values and we actively engage to be a university where you feel at home and can flourish. We value different perspectives and qualities. We believe this makes our work more innovative, the TU Delft community more vibrant and the world more just. Together, we imagine, invent and create solutions using technology to have a positive impact on a global scale. That is why we invite you to apply. Your application will receive fair consideration.

Challenge. Change. Impact!

The Faculty of Electrical Engineering, Mathematics and Computer Science (EEMCS) brings together three scientific disciplines. Combined, they reinforce each other and are the driving force behind the technology we all use in our daily lives. Technology such as the electricity grid, which our faculty is helping to make completely sustainable and future?'proof. At the same time, we are developing the chips and sensors of the future, whilst also setting the foundations for the software technologies to run on this new generation of equipment - which of course includes AI. Meanwhile we are pushing the limits of applied mathematics, for example mapping out disease processes using single cell data, and using mathematics to simulate gigantic ash plumes after a volcanic eruption. In other words: there is plenty of room at the faculty for ground?'breaking research. We educate innovative engineers and have excellent labs and facilities that underline our strong international position. In total, more than 1000 employees and 4,000 students work and study in this innovative environment.

here to go to the website of the Faculty of Electrical Engineering, Mathematics and Computer Science.

This PhD position is positioned within the Delft Bioinformatics Lab, part of the Computer Science department of the Delft University of Technology under supervision of Prof. Marcel Reinders, , and Ahmed Mahfouz from the Leiden University Medical Center, , in close collaboration with BRAINSCAPES scientists across the Netherlands.

Are you interested in this vacancy? Please apply via the application button and upload the following documents:

• An up?'to?'date and detailed curriculum vitae.
• Copies of relevant academic transcripts.
• A cover letter, which should summarize (1) why the applicant wants the position, (2) why the project is of interest to the applicant, (3) evidence of suitability for the job, and (4) what the applicant hopes to gain from the position.

Doing a PhD at TU Delft requires English proficiency at a certain level to ensure that the candidate is able to communicate and interact well, participate in English?'taught Doctoral Education courses, and write scientific articles and a final thesis. For more details please check the Graduate Schools Admission Requirements.

Please note:

• You can apply online. We will not process applications sent by email and/or post.
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