PhD student – Immune landscape and immunotherapy for ependymoma: a single cell and spatial transcriptomic approach

We are seeking an enthusiastic, highly motivated PhD candidate to join our group. The project aims to characterize ependymoma tumor cells and its tumor microenvironment (TME) on a single cell level. The goal of the project is to use this knowledge of the immune landscape to develop better immunotherapy approaches. You will be working in a stimulating, multi-disciplinary research environment with international collaborations. Are you willing to take on the challenge?

The research project

Ependymomas are brain tumors that primarily affect children. Despite intense treatments like surgery, radiation, and sometimes chemotherapy, the survival rates remain low because some cancer cells survive treatment and cause the tumor to relapse. Furthermore, these therapies lead to long-term problems for children, including difficulties with memory, learning, and daily activities. Hence, there is an urgent need for more effective and less harmful treatments.

Novel immunotherapies, such as CAR-T cell-based approaches, show promise in various tumor types, such as leukemia, due to low toxicity and sustained efficacy. However, thus far they remain ineffective in ependymoma and other pediatric brain tumors, most likely due to the immunosuppressive TME and suboptimal targeting of tumor cells by therapy.

This project will use state-of-the-art single-cell and spatial transcriptomics to characterize ependymoma and its immune TME. You will perform these experiments and analyze the composition, differentiation, and activation states within the TME and tumor cells. By comparing samples from different stages of disease, from different molecular ependymoma subtypes, and from other pediatric brain tumors, you will characterize the myeloid (resident microphages and bone marrow-derived macrophages) and lymphoid compartment to find commonalities and differences in cellular composition, spatial organization and cell state. Furthermore, you will investigate potential alternative targets for immunotherapies or for reprogramming of the immune TME. Overall, the goal is to reveal the molecular underpinnings of TME heterogeneity and identify potential targets for therapeutic intervention.

The project is part of a larger international program funded by the Brain Tumour Charity. There will be complementary data for including in the analyses that is being generated with the Máxima or by our international collaborators. These include, for instance, in vitro and in vivo experiments, proteomic analyses (spectral-flow cytometry and cyclic immunofluorescence), and additional transcriptomic data. Within the Kool group, you will work closely together with an Bioinformatic Postdoc and will be supported by research technicians. Furthermore, you are expected to actively collaborate within the international programs, as well as the collaborating research group and physicians in the Máxima.

Your profile

We are looking for an enthusiastic and highly motivated PhD candidate, who is eager to spearhead this project, with the following qualifications and skills:

• A Master of Science degree or equivalent in bioinformatics, (molecular) biology, biomedical sciences, immunology, or related disciplines.
• Demonstrated experience with coding and bioinformatic analyses of transcriptomic and/or imaging data is essential. Knowledge of Python or R is preferred.
• Demonstrated wet lab experience is essential. NGS experiments or advanced imaging, such single cell or spatial transcriptomic experiments, is preferred.
• Knowledge about immunology and/or (pediatric) brain tumor is preferred but not required.
• A strong motivation, attention to detail, flexibility, well-organized and good data management skills are critical.
• The ability to work independently as well as collaborative in multidisciplinary and multicultural research teams.
• Excellent English written and verbal communication skills.

Our job offer

We offer you a temporary, full-time PhD-position for a total duration of 4 years (36 hours / 5 days a week) in our group. You will also collaborate with various research groups at the Princess Máxima Center and abroad. You will initially be contracted for a period of 1 year, with a possible extension. Your gross monthly salary will start in FWG 45-6 with a salary of €3.665,- gross a month for a fulltime working week (36 hours). You also receive 8.33% holiday allowance and 8.33 % end-of-year bonus. The Princess Máxima Center operates according to the collective labor agreement 'CAO ziekenhuizen'.

About our group

Our research group, headed by Professor Marcel Kool together with Dr Jens Bunt, studies the (epi)genomics and transcriptomics of pediatric brain tumors and how to translate findings from these studies into novel therapies. More effective and less toxic therapies are urgently needed. For many types of childhood brain tumors, the survival is still very poor, and survivors suffer from serious long-term side effects caused by their intensive therapies. To develop such new therapies, we need better understanding of tumor development and biology as well as molecularly well-characterized preclinical models that represent the broad intra and inter-tumor heterogeneity. We focus on ependymomas, medulloblastoma and rare embryonal and sarcomatous tumors of the brain. Using (epi)genomic and (single cell) transcriptomic analyses of tumors and normal developing brain, we study tumor biology, tumorigenesis and the tumor environment. Utilizing organoid technology and recent advances in neuroscience, we are also generating advanced patient-derived models and genetically induced tumor models derived from brain organoids. We use these data and models to accelerate the translation of our biological findings to get more effective therapies for patients.

The Princess Máxima Center

The Princess Máxima Center for Pediatric Oncology is an integrated hospital and research institute, which integrates healthcare, research and education on pediatric cancer, in a single location in Utrecht. Our institute aims to provide the highest level of care for all children with cancer, with optimal quality of life. The center brings together the best possible care and scientific research, creating a unique interdisciplinary institute for pediatric oncology in Europe.

Apply for this position?

Are you interested in becoming our new PhD student? You can apply directly by clicking the orange button on this page. We encourage you to apply as soon as possible, as the vacancy will be closed once we have received a sufficient number of applications.

Please provide:

• an up-to-date resume
• a short motivation letter (2 pages maximum)
• contact information of 2-3 references.

Incomplete applications will not be considered.

For more information about our group, please visit this link. Do you have any questions, or would you like more information about this position? Please contact Dr Jens Bunt. Jens will be happy to tell you more

Acquisitie naar aanleiding van deze vacature wordt niet op prijs gesteld.

• • 36 hours per week
• • FWG: 45 - 6
• • €3.665,-

Jens Bunt