PhD student - Decoding Epigenetics in T cells to Improve Cancer Therapy

The group of Fred van Leeuwen is looking for a PhD candidate to join our team working on mechanisms and functions of epigenetic pathways in cancer development and treatment. In this project funded by KWF, you will study how targeting an epigenetic writer protein called DOT1L reprograms cytotoxic T cells. T cells are a crucial players in anti-tumor responses, but tuning their activity remains a challenge. By understanding the epigenetic mechanisms by which DOT1L works, we hope to ultimately strengthen T cells so they can fight cancer cells more effectively.

CD8 T cells play a central role in cancer immunotherapy. We recently observed that inactivation of the epigenetic writer DOT1L in CD8 T cells leads enhanced cytotoxic activity towards tumor cells in vitro. DOT1L is known to methylate histones at position H3K79 in gene bodies of transcribed genes. However, if and how this epigenetic marking influences cytotoxic behavior is still poorly understood. This knowledge gap hinders developing rational approaches to target the DOT1L-controlled program with the aim to further improve T cell therapy.

In this research project you will:

• Apply innovative and complementary strategies in a tractable human T cell model, including CRISPR-Cas9–based genome engineering, epigenomics and transcriptomics, unique DNA-barcode–based epigenetic screens in yeast;

• Validate identified targets in primary human CD8 T cells;

• Gain molecular insights to provide leads for improved epigenetic perturbation of CD8 T cells to enhance cytotoxic activity towards cancer cells.

Why the Netherlands Cancer Institute?

Netherlands Cancer Institute (NKI) is a dynamic comprehensive cancer center accommodating over 55 research groups and many state-of-the-art core facilities, including imaging, flow cytometry, proteomics, genomics and screening. At the Netherlands Cancer Institute, we have a shared goal: providing the best care for every patient and every type of cancer. Quite a lot, but not impossible. Here, science and health care join forces towards innovation. We keep finding new ways to help people facing cancer on a global scale.

If the challenge appeals to you and you recognize yourself in the conditions below, we would like to invite you to apply. We are looking for a colleague who meets the following criteria:

• A MSc degree in (molecular) biology or a related discipline (e.g. medical biology, cancer biology, genetics);

• Demonstrable experience with basic molecular biology techniques;

• Affinity for (or ideally experience with) computational biology;

• Fluent in academic English, both spoken and written;

• Prior experience (e.g. internship) in the field of gene regulation / chromatin biology is an asset

• Can work independently with a problem solving attitude;

• Excellent social and communication skills and can work in collaboration with others in an international team;

• Interested in fundamental mechanistic research in the context of immunology and cancer therapy.

Your development opportunities and employment conditions

The basis for your employment conditions is in accordance with the CLA Hospitals. You will receive from us:

• A temporary contract for a period of four years, for 36 hours per week

• A gross monthly salary between € 3.665,- and € 4.450,-, based on a 36-hour working week, in line with FWG45 and depending on your experience;

• 144 holiday hours and 57 hours of Personal Life Budget, with full-time employment;

• Annual holiday pay of 8.33% and a fixed end-of-year bonus of 8.33%;

• A travel allowance of €0.23 per km;

• Free parking at the Netherlands Cancer Institute. And with our bicycle plan and discount on public transport we also make it attractive for you to leave the car at home;

• An environment where you can continue to learn and develop you personal and professional skills;

• Opportunity to exercise during working hours at our Fit Boutiqs;

• An active PhD council;

• A cutting-edge dynamic and international research environment;

• Opportunities to collaborate with scientists in different disciplines;

• A training and supervision plan and courses offered by the Oncology Graduate School Amsterdam (OOA).

Interested?

We are curious about your talent! Will you be the one to make a difference in the world of cancer care and research? You can apply by clicking the apply (solliciteer) button at the top of the page. Include in your application:

• Application letter, explaining why you are excited about this PhD position, and what experience and personal qualities make you a strong candidate;

• CV, including your grades. If you don’t have a MSc certificate yet, explain briefly what you still need to complete and provide your expected graduation date;

• Contact information of 2 references. Provide name, email address, phone number (do not submit reference letters).

Ensure that your references information and an overview of your grades are attached together with your application letter or CV, as there is no option to submit them separately.

For questions about the position, please contact Fred van Leeuwen via fred.v.leeuwen@nki.nl.

Our group is part of the Division of Gene regulation, which focuses on (epigenetic) mechanisms of genome-organization and gene transcription. We work in close collaboration with the Division of Molecular Oncology and Immunology, for complementary expertise on immune cell biology, genetic modification and phenotyping of T cells, and T cell therapy.

This vacancy is open for applications until November 1st 2025. Qualified candidates may be invited prior to the application deadline.