PhD position (Epigenetics & Gene Regulation): Deciphering Chromatin-Based Oncogenic Mechanisms in NPM1 mutant Leukemia

The IPP Mainz summer call 2019 is open.

Thinking of doing your PhD in Molecular Biology? The International PhD Programme (IPP) on “Epigenetics, Gene Regulation & Genome Stability” is offering talented, young scientists the chance to work at the cutting edge of research. The IPP has a community of exceptional scientists working on diverse topics. These range from how organisms age or how our DNA is repaired, to how epigenetics regulates cellular identity or neural memory. This means that no matter where your PhD project takes you, there is always someone to go to for advice or collaborations.

As part of the IPP, you will be given advanced training, covering skills needed for both research and industry. Access to our state-of-the-art Core Facilities and their technical expertise ensures that you are supported no matter how challenging or expansive your project becomes. Importantly, as an IPP student, you are offered a fully funded position with financing until the completion of your thesis. To help you integrate and settle in Mainz, IPP students organise and run a lively social programme with activities to suit everyone.

The IPP is coordinated by the Institute of Molecular Biology (IMB) —a modern research centre located on the bustling campus of Mainz University in Germany. The IPP currently has over 120 energetic students from 30 countries working on innovative research at IMB, Mainz University and its University Medical Centre.

Are you an ambitious, young scientist looking to push the boundaries of science while interacting with colleagues from multiple disciplines and cultures? Then the IPP is your opportunity to give your scientific career a flying start!

Activities and responsibilities

In the field of “Epigenetic Dependencies in Leukemia’’, the IPP research group of Dr Michael Kühn offers the following PhD project:

Deciphering Chromatin-Based Oncogenic Mechanisms in NPM1 mutant Leukemia

Acute myeloid leukemia (AML) is a disease originating from early hematopoietic progenitors that are characterized by a block of differentiation and clonal expansion. Mutations in the nucleophosmin (NPM1) gene are the most common recurrent mutations in AML and can be found in one third of the cases. The Kühn lab recently reported that leukemogenic gene expression programs in NPM1 mutant AML are dependent on the menin-MLL1 (KMT2A) chromatin complex. The menin-MLL1 interaction further represents a therapeutic opportunity in these leukemias and can be targeted via novel small molecule inhibitors.
The overarching goal of this PhD project is to explore the mechanisms how the mutant NPM1 protein and the menin-MLL1 chromatin complex drive leukemogenesis. You will assess human and murine models of NPM1 mutant leukemia for global changes in gene expression following genetic inactivation of NPM1 or menin-MLL1 using CRISPR/Cas9. These results will then be integrated with assessment of histone marks and chromatin state using next generation sequencing techniques. Findings from the genetic inactivation study of menin-MLL1 will be validated using pharmacological inhibition of the menin-MLL1 interaction. The functional effects inactivation of these proteins on cell proliferation, differentiation as well as leukemia initiating capability will be assessed in vitro and in vivo.
This project is most suitable for a PhD student who aims to ask fundamental biological questions about how chromatin-based mechanisms drive oncogenic processes and would like to work on a translational topic that may have the potential to directly affect how patients with leukemia are being treated.

Qualification profile

Required qualifications
  • Master or equivalent
  • Motivation to work at the forefront of science
  • Interactive personality & good command of English
  • 2 letters of reference

Benefits

We offer
  • The possibility to work on exciting, multidisciplinary projects using state-of-the-art technology in highly motivated research teams
  • To be part of a lively and international community of about 120 IPP students from 30 countries
  • Numerous opportunities for advanced professional training in scientific knowledge, techniques and professional skills
  • Fully funded positions until completion of thesis
Starting date: 1 August 2019 – 1 February 2020
Duration of stipend/salary: 3 years, with the possibility of extension

Deadline for registration (exclusively online via web form): 22 May 2019

Send application to

Please find all relevant information on the application process at: http://imb.de/ipp-reginfos

Bitte beziehen Sie sich bei Ihrer Bewerbung auf jobvector und geben Sie die folgende Referenznummer an: JV-C17-MK

Über Institute of Molecular Biology gGmbH

Our International PhD Programme on the “Gene Regulation, Epigenetics and DNA Damage Response” gives talented and enthusiastic students the opportunity to undertake PhD research at the cutting edge of modern biology. Our groups cover a broad range of expertise and include leading biochemists, geneticists, cell and developmental biologists who study the molecular mechanisms of embryonic...

Mehr über Institute of Molecular Biology gGmbH