Thinking of doing your PhD in the Life Sciences? The International PhD Programme (IPP) Mainz is offering talented scientists the chance to work on cutting edge research projects within the open call on “Molecular Mechanisms in Genome Stability & Gene Regulation”. 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.

Activities and responsibilities

The research group of Sandra Schick offers the following PhD projects:

Genomic DNA is highly compacted into chromatin in order to fit into the nucleus of a cell. The packaging further provides a regulatory layer for DNA accessibility and therefore all DNA-dependent processes, such as transcription, DNA repair or replication. ATP-dependent chromatin remodellers can modulate the accessibility by moving or evicting nucleosomes. One class of these remodellers are the BAF complexes, very large multi-protein complexes existing in many different configurations in human cells. Their importance is highlighted by the fact that mutations in genes coding for these complexes are found in more than 20% of all human cancers and are frequently causative for developmental diseases. For example, heterozygous mutations in several genes encoding BAF subunits are often the cause of neurodevelopmental disorders such as Coffin-Siris-Syndrome, Nicolaides-Baraitser-Syndrom or Autism spectrum disorder. They manifest as brain abnormalities, intellectual disabilities and other physical aberrations. The molecular and cellular consequences of these mutations are hardly known so far. Therefore, understanding the cell type-specific composition and function of these complexes in the development of the brain as well as the cellular changes caused by the mutation of a subunit is of great importance for the development of therapeutics against these common BAF-mutated diseases.

PhD project: Gene regulation by chromatin remodellers during neurodevelopment and related disorders

BAF complexes control the accessibility of cell type-specific genomic gene regulatory regions and are therefore of great importance for developmental processes, cell fate transitions during differentiation and cell maintenance. To understand their physiological role during human brain developmental processes and unravel disease-associated molecular alterations caused by mutations in genes encoding subunits of these complexes, we will implement stem cell differentiation into brain organoids combined with molecular perturbation tools such as CRISPR/Cas9 and chemically induced protein degradation. This will allow us to model developmental diseases and unravel the physiological role of BAF subunits and specific BAF complexes in human developmental processes. With the help of bulk and single-cell genomics, proteomics, molecular biology, screening and imaging approaches, we will then dissect the cellular and molecular consequences upon loss of selected BAF subunits. This will provide novel insights into these diseases as well as the function of the BAF complexes and their subunits in developmental processes.

We are therefore looking for a highly motivated PhD student who is experienced in the lab, enthusiastic about science especially with regard to neurodevelopmental processes, gene regulation and epigenomics and has a strong interest in tackling scientific questions in an interdisciplinary way. Computational skills are an asset but not compulsory.

In addition, we are looking for a computational PhD students experienced in NGS data analysis, beneficially for bulk and single cell experiments, data integration and visualization.

The project is funded by an ERC starting grant.

If you are interested in the wetlab position of this project, please select Schick (Bench) as your group preference in the IPP application platform.

If you are interested in the computational position of this project, please select Schick (Comp) as your group preference in the IPP application platform.

Qualification profile

Are you an ambitious 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

We offer

• 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 www.imb.de/phd.

The deadline for applications is 24 October 2024. Interviews will take place at IMB in Mainz on 20-22 January 2025.
Starting date: 1 March 2025 - 1 July 2025