PhD position: Interactions between the hematopoietic system and the bone marrow in aging (m/f/d)
Institute of Molecular Biology gGmbH
Location
Ludwigshafen am Rhein | Germany
Job description
Thinking of doing your PhD in the Life Sciences? The International PhD Programme (IPP) Mainz is offering talented, young scientists the chance to work on cutting edge research projects within the open call on “Molecular Biomedicine & Ageing” . As an IPP PhD student, you will join a community of exceptional scientists working on diverse topics ranging from how organisms age or how our DNA is repaired, to how epigenetics regulates cellular identity or neural memory.
Aufgaben:
The research group of Wolfram Ruf offers the following PhD project:
Throughout life, a finely regulated balance between quiescence and activation allows the hematopoietic stem cell (HSC) to continuously replenish all mature blood cells in homeostasis and in response to challenges. However, in aging HSCs become dysfunctional and show differentiation imbalances toward an increased production of myeloid cells at the expense of the adaptive immune lymphocytes. This has been associated with an increased risk of age-related conditions including cardiovascular complications, impaired immune responses, and myeloid premalignancies. The changes in aging HSCs result not only from accumulation of cell intrinsic insults but also from cell extrinsic effects. Within the bone marrow (BM), HSCs interact with several cellular and matrix (growth factors, extracellular vesicles) components which are crucial in the regulation and maintenance of HSC fate. While it has been shown that aged HSC can be partially rejuvenated once exposed to a young BM microenvironment, it is not clear which environmental cues contribute to the aging of the hematopoietic system. Proteases of the coagulation system have been implicated in the regulation of HSC fate (extravascular coagulation signaling) in homeostatic condition as well as in aging mouse models. Characterization of these interaction could provide new approaches to counteract or delay age-associated exhaustion of HSC.
PhD Project: Impact of intercellular interaction within the bone marrow microenvironment on hematopoiesis during aging The aim of the project is to determine the contribution of interactions within the BM microenvironment (e.g. mesenchymal stromal cells and endothelial cells) to disrupted HSC function and unbalanced hematopoiesis in aging. Ultimately, the long-term goal will be to identify targets for the development of rejuvenation strategies. The work of the PhD candidate will include the interrogation of single cell sequencing datasets (established in the host lab) of young and old hematopoietic progenitors in different mouse models with an accelerated aging phenotype. This will lead to the identification followed by validation, via application of state-of-the-art BM imaging and functional assays, of possible regulators of age-associated reprogramming. Furthermore, different mouse models with accelerated senescence in stromal cells will be employed to address the impact of the BM microenvironment on aging of HSC. Characterization of the senescent associated secretory phenotype BM environment (e.g. of extracellular vesicles) may also be required to identify underlying molecular mechanisms for altered interaction that affects HSC output in aging.
A sound knowledge in molecular and cell biology and/or protein chemistry and an interest in working with animal models are expected for successful candidates. The candidate should have an interest in systems biology approaches and develop skills to apply bioinformatics on newly generated and available omics data sets for further validation in in vivo models of aging. This will be an interactive project involving different research groups which provide a variety of learning opportunities and interdisciplinary approaches.
If you are interested in this project, please select
Ruf as your group preference in the IPP application platform.
Qualifikationsprofil:
Are you an ambitious, young scientist looking to push the boundaries of research while interacting with colleagues from multiple disciplines and cultures? Then joining the IPP is your opportunity to give your scientific career a flying start!
All you need is:
- Master or equivalent
- Interactive personality & good command of English
- 2 letters of reference
Benefits:
- Exciting, interdisciplinary projects in a lively international environment, with English as our working language
- Advanced training in scientific techniques and professional skills
- Access to our state-of-the-art Core Facilities and their technical expertise
- Fully funded positions with financing until the completion of your thesis
- A lively community of more than 200 PhD students from 44 different countries
For more details on the projects offered and how to apply via our online form, please visit .
The deadline for applications is 17 April 2024. Interviews will take place at IMB in Mainz on 1-3 July 2024.
Starting date: 1 August 2024 - 1 January 2025
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