Postdoc Leukaemic Fusion Genes Group

Heidenreich Group

Background information about the Leukaemic Fusion Genes Group

Fusion gene-encoded transcriptional regulators such as RUNX1/ETO drive leukaemias by corrupting haematopoietic gene expression. These dysregulated programmes comprise gene products whose continuous expression is required for maintaining leukaemia. This scenario suggests two ways of interfering with fusion genes: directly by inhibiting their expression and indirectly by perturbing their downstream programme. By combining genomic and gene expression data with RNAi and CRISPR screens, we functionally identify crucial “transmitters” of fusion genes that are potentially suitable for indirect targeting (Martinez-Soria et al., 2018, Cancer Cell; Assi et al., 2019, Nat. Genetics). In addition, we have developed a liposomal approach for the in vivo delivery of siRNAs that directly target these fusion transcripts. Moreover, we are refining complex co-culture conditions and immunodeficient mouse transplantation models for the functional interrogation of primary material derived from AML patients (Pal et al., 2016, Leukemia; Elder et al, 2017, Leukemia). Our findings suggest that RUNX1/ETO also controls leukaemic adhesion and migration and affects the interaction between leukaemic cells and the niche including MSCs. Our ultimate aim is to develop more disease-targeted, patient-specific and less toxic treatment options for patients and, in particular, for children with leukaemia.

Project

This project will validate downstream mediators of leukaemic fusion proteins by examining their contribution to the leukaemic phenotype in tissue culture and in vivo. By combining ChIP-seq and RNA-seq analyses with RNAi screens in vivo we have identified and functionally interrogated downstream targets of RUNX1/ETO as a paradigm for a leukaemic fusion gene. These in vivo RNAi screens have identified genes that are likely to be crucial mediators of fusion gene-driven AML growth. To elucidate underlying mechanisms in PDX, you will use state of the art co-culture and mouse transplantation models and system based on RUNX1/ETO patient-derived xenograft material generated from AML patients. Applied techniques will include lentiviral transduction of PDX, RNAi and CRISPR-mediated gene knockdown and knockout and performing and analysing next generation sequencing experiments.

Tasks and responsibilities

We are looking for an enthusiastic candidate enjoying intellectual challenge and out-of-the-box thinking. You have substantial skills in molecular biology and cell biology. Expertise in animal models, in particular immunodeficient mouse models, or basic bioinformatics skills are a strong plus. You will join a newly established research team at the Maxima closely interacting with an established research team in Newcastle, UK. Both teams are jointly led by Olaf Heidenreich as PI and Josef Vormoor (Clinical Director of Hemato-oncology at the Maxima) as Co-PI.

Skills

  • PhD or equivalent doctoral degree in a relevant scientific area
  • Experience in contemporary cell biology/molecular biology techniques
  • Experience in the ex vivo culture of primary cells
  • Experience in the analysis of gene function
  • Excellent publication record in peer-reviewed journals
  • Experience in in vivo work, particularly in PDX transplantation of immunodeficient mice
  • Excellent analytical and problem-solving skills
  • Team membership skills within multidisciplinary research teams
  • Excellent communication and presentation skills
  • Ability to demonstrate commitment to a research career and evidence of development towards group leadership

Working at the Princess Maxima Center for pediatric Oncology

We offer a full-time position based on 36 hours per week. You will start on a temporary position for the duration of two years that—when satisfactory—will be extended for a total of 5 years. Salary is based on postdoc salary scales depending on years of experience. The Princess Máxima Center operates according to the collective labor agreement ‘cao algemene ziekenhuizen’.

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You can apply for this position until the 1st of March by pressing the apply button on this screen.

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

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