PhD - Pathogenesis of stem cells tumorigenicity (1.0 FTE)
Universiteit Utrecht
Utrecht, NL
5 dagen geleden

Functie We are looking for an enthusiastic, driven and highly motivated PhD candidate to perform scientific research on mechanisms of tumorigenicity of stem cells.

Similar to human embryonic stem cells (hESCs), induced pluripotent stem cells (hiPSCs) can be maintained in culture indefinitely (self-renewal) and differentiate into virtually all cell types of the human body (pluripotency).

Since they capture the genotype of the donor, hiPSCs are already used successfully for studying mechanisms of disease and for drug testing.

The fact that hiPSCs can be generated from any human individual makes the concept of personalized medicine a realistic goal.

However, the presence of residual, potentially malignant cells among the cell population being transplanted represents a serious safety issue and requires rigorous testing and identification of unsuitable hiPSC lines beforehand.

Stem cells are key to our normal development and health from conception through adulthood. Stem cells survive much longer than ordinary cells, increasing the chance that they might accumulate genetic mutations.

It might take only a few mutations for one cell to lose control over its self-renewal and growth and become the source of cancer.

Currently, the potential tumorigenicity of hiPSCs is tested by injecting cells into mice where they either form benign teratomas or malignant teratocarcinomas.

However, the Teratoma tumorigenicity assay is animal-dependent, costly, time-consuming and only qualitative and has never been standardized.

Since the number of hiPSC lines is steadily rising and (pre)clinical studies are already on their way, there is an

urgent need for a new quantitative gold standard assay which is animal-independent. Gene networks guarding stemness and differentiation potency are dysregulated in case of resistant and metastatic tumors leading to transformation of tumor cell into cancer stem cells.

We have recently shown that the presence of malignancy related miRNAs such as miR-371 in liquid biopsies has been proven a useful tool for reporting undifferentiated components of malignant teratomasand in diagnostics of human tumors.

This project aims to develop and validate in vitro assays based on microRNAs which is able to predict the tumorigenicity of hiPSCs and could therefore replace the in vivo tests and ultimately to study mechanism of tumorigenicity.

Furthermore we will study the mechanism underlying stemness and malignant transformation in different types of human and animal tumors.

Used techniques will include :

  • cell culture of stem cells, including 3D cultures and 3D culture assays organoids;
  • microRNA analysis;
  • single cell analysis including bioinformatic tools;
  • generation of induced pluripotent stem cell lines using CRISPR / Cas9 system;
  • histology, advanced microscopy, FACS.
  • Profiel We are looking for a creative and independent thinker, who can deepen a research question, an excellent communicator (both orally and in writing), and a team player.

    You will join an international team, therefore fluency in English is required. Your findings will be published in peer reviewed journals and you will present your work in the department and at international conferences.

    Experience in cancer research, molecular and cellular biology, and with in vitro models such as stem cells / organoids will be an advantage.

    Aanbod We offer a position (1.0 FTE) for a period of four years in an international working environment. The gross salary ranges from €2,395 in the first year to €3,061 (scale P according to the Collective Labour Agreement Dutch Universities) in the fourth year per month for a full-time employment.

    Salaries are supplemented with a holiday bonus of 8% and a year-end bonus of 8.3% per year. In addition, Utrecht University offers excellent secondary conditions, including an attractive retirement scheme, (partly paid) parental leave andflexible employment conditions (multiple choice model).

    More information about working at Utrecht Universitycan be foundhere.

    In addition, we offer an exciting opportunity to contribute to an ambitious and international research programme with highly motivated students and to conduct your own research project at a renowned research university.

    You will receive appropriate training, personal supervision, and guidance for both your research and teaching activities, which will provide an excellent start to an academic career.

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