PhD on PURA Syndrome

Our Lab

The Niessing lab at Ulm University is a multidisciplinary team with expertise ranging from structural biology, biophysical interaction studies to high-through-put approaches and stem cell-based research. Doing a PhD in this unusually multidisciplinary setting will expose you to a wide range of methods and yields a holistic views on biological questions. This breath of approaches is further supported by close interactions with the Niessing lab at the Helmholtz Zentrum München.

One of our core projects is the PURA Syndrome, caused by heterozygous mutations in the PURA gene. The resulting PURA protein is involved in major cellular processes including transcription, mRNA transport and translation. Defects in the PURA gene cause neurodevelopmental delays, leaving the patient with intellectual disability, difficulties with motion, and epileptic seizures. First diagnosed in 2014, today about 550 patients are known worldwide. Several of the affected families are organized in the international PURA Syndrome Foundation (www.purasyndrome.org/) and the PURA Syndrome Deutschland Foundation e.V. (https://pura-deutschland.de/), with whom we are in regular contact.

PhD candidate - the neurodevelopmental disorder PURA Syndrome (f/m/x)

Your Mission

The Niessing group has established a broad research program on the PURA Syndrome to understand the molecular action of PURA and the cause of symptoms in patients. Using X-ray crystallography, we study the structure of PURA alone and when bound to other factors. In immortalized cell lines and in induced pluripotent stem cells (iPSCs) we employ high-throughput techniques to assess the interactome of PURA. This way, we have established a large amount of data as basis for the announced PhD position. In addition, we wish to understand the co-regulation of PURA by its sister genes PURB and PURG, hoping that this leads to a new therapeutic window for patients with PURA Syndrome.

A major task of your thesis will be to assess how PURA, PURB, and PURG are (co-) regulated and if this can be used for therapeutic purposes. This will involve, for instance, CRISPR-knock-out studies in stem cells followed by cell-biological approaches such as antibody staining and high-throughput studies such as RNA-seq and shot-gun proteomics. In addition, you will establish a cell-based reporter system towards a systematic screen for therapeutic intervention in PURA patients. In summary, this thesis will offer an unusually wide spectrum of techniques and will be embedded in an exciting research program. Furthermore, our annual PURA patient meetings will allow you to meet affected families.

For further details, please see
Molitor et al. Front Genet, (2021) (https://doi.org/10.3389/fgene.2021.638217) and
Molitor et al. Nucl. Acids Res. (2023) (https://pubmed.ncbi.nlm.nih.gov/36651277/).

Your profile

- Appropriate studies (Master of Science / Diploma) in biology, biochemistry or related disciplines
- Expertise in human/mouse cell culture
- Biochemical experience is of advantage
- Strong interest and ambition to learn about RNA-based regulatory networks and related diseases
- Knowledge of molecular biology
- High motivation, flexibility and teamwork

Interested?

If you have further questions or wish to apply, please contact Prof. Dr. Dierk Niessing at dierk.niessing(at)uni-ulm.de

For applications to be considered, they should contain a letter of motivation, a CV, transcript of records, and – if possible - contact information of two scientists who are willing to provide reference for you.