Stem cells are generally small, glycolytic cells with low numbers of mitochondria. In contrast, differentiated cells are large with high numbers of mitochondria that rely on OXPHOS, the most efficient source of cellular energy. As undifferentiated cells differentiate into distinct mature cell types, a specific number of mitochondrial DNA(mtDNA) copies, the set point, serves as template for mtDNA replication. This change can be observed during normal development in multicellular organisms, but is also a critical step in tumor development and progression. The increase in the number of mitochondria during differentiation is accompanied by changes in size and morphology of the cell. While it is evident that subcellular mitochondrial organization and structure is important to meet and maintain the changing metabolic demands of the differentiating tissue, it is largely unknown how the cells remodel their metabolism structurally.

The aim of this project is to study and image the subcellular mitochondrial changes underlying the changing metabolic needs of differentiating cells. The PhD student will combine genetic and enzymatic experiments on mitochondrial (dys)function in human cell lines and zebrafish with innovative and advanced optical microscopy, such as super-resolution (STED) microscopy and intravital two-photon and second harmonic laser scanning microscopy (TPSHLSM). The PhD student will study the differentiation process during embryonic development in zebrafish, during stem-cell differentiation in patient-derived iPSCs, and during the de-differentiating and re-differentiating process in glioblastoma cells.

            Required:

• Enthusiastic person with strong interdisciplinary profile to join our team of PhD Students

• Completed Master’s study in Biomedical Sciences, Biology, or a related relevant study

• Eager to perform research in a multidisciplinary team at the crossroads of biomedical sciences, with special emphasis on genetics, zebrafish, stem cell technology, and imaging.
  
  Preferred:

• Experience with molecular genetics and genomics techniques

• Experience with stem cell technology and cell culture

• Experience with advanced optical imaging techniques

• Experience with zebrafish

Fixed-term contract: 4 years.

The terms of employment of Maastricht University are set out in the Collective Labour Agreement of Dutch Universities (CAO). Furthermore, local UM provisions also apply. For more information look at the website 

After the 1st year, a go/no-go decision will determine whether the candidate is allowed to continue his/her PhD research for the next three years. Each year an evaluation takes place.

GROW-School for Oncology and Development

GROW is the School for Oncology and Developmental Biology at the Maastricht University Medical Centre (MUMC+) and accredited by the Royal Academy of Arts and Sciences (KNAW). GROW focuses on research and teaching of (epi)genetic and cellular concepts, as well as (micro)environmental factors underlying normal and abnormal development. As such the basic mechanisms of embryogenesis and fetal growth, as well as those governing the process of carcinogenesis are subject of study within GROW. The project is embedded in the GROW-research line “Mitochondrial Genetics”, which focuses on the characterization of:

1. Abnormalities in mitochondrial genes, gene expression, and gene function in inherited and complex diseases, like neuromuscular disorders and neurological syndromes, in human patients and animal models.

2. Interventions that can modulate mitochondrial activity and promote health and prevent or ameliorate disease manifestations.

3. Preventing the transmission of OXPHOS disease due to mutations in the mitochondrial DNA by pre-implantation genetic diagnosis (PGD).

The research program that goes from bedside to bench and back, is highly technology and bioinformatics driven. It covers fundamental, translational, and applied research alike.

            The PhD student will be working at the Department of Genetics and Molecular Cell Biology. At Molecular Cell Biology (MCB), advanced optical microscopy has a long tradition. Since 2015, MCB is a driving force behind EuroBioImaging Node Candidacy “Maastricht Excellence in Imaging.

http://www.grow-um.nl