PhD Student
PhD position (Ageing & Disease, Bioinformatics & Computational Biology): Prediction and experimental validation of molecular mechanisms that underlie brain-specific phenotypes of NDDs Full-time
Thinking of doing your PhD in Molecular Biology? The International PhD Programme (IPP) on Gene Regulation, Epigenetics & Genome Stability is offering talented, young scientists the chance to work at the cutting edge of research. The IPP is 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.
The programme is coordinated by the Institute of Molecular Biology (IMB) — a modern research centre located on the bustling campus of Mainz University in Germany. With a population of 200,000, of which about 40,000 are students, the city of Mainz is charming and open-minded and is within easy reach of cosmopolitan Frankfurt, the Rhine valley region with its castles, vineyards, and nature reserves, and the equally picturesque cities of Wiesbaden and Heidelberg. With Frankfurt airport – the largest airport in mainland Europe – only 20 minutes away, countless European and overseas destinations are within easy reach.
Activities and responsibilities:
In the field of “Ageing & Disease”and “Bioinformatics & Computational Biology”, the IPP research group of Dr Katja Luck offers the following PhD project:
Prediction and experimental validation of molecular mechanisms that underlie brain-specific phenotypes of NDDs
More than 1000 Mendelian diseases are known that show disease manifestation in only one tissue. This tissue specificity seems surprising given that every cell of an affected individual carries the disease mutation. This tissue-specific phenotype could be explained by the mutated gene being only expressed in the affected tissue. However, this was only found to be the case for 20% of these diseases. Among the other 80% are neurodevelopmental disorders (NDDs), which comprise syndromes such as intellectual disability, developmental delay, autistic behaviour, and epilepsy. Mutations that have been associated with NDDs are primarily protein-coding but the molecular mechanisms underlying the brain-specific phenotype of NDDs remain largely unknown. Myself and others have hypothesized that tissue-specific phenotypes can also be caused by perturbation of an interaction between a broadly expressed “disease gene” and a tissue-specifically expressed interaction partner. However, brain-specific protein-protein interaction data are very sparse due to the difficulties in determining protein interactions endogenously at higher throughput.
PhD project
Myself and others have shown that the cellular context of protein interactions, which were determined in an exogenous expression system, can be inferred via integration of protein interactions with gene and protein expression data. This has allowed to successfully explore cellular context-specific functions of proteins. The aim of the project is to further refine approaches for cellular context-specific protein interaction network inference using available tissue, cell type and single cell RNAseq and proteome data of the human and mouse brain on one side, and recently generated proteome-scale human protein interaction resources on the other. These approaches will be applied to predict potential molecular mechanisms that mediate the brain specific functions of NDD-related proteins. Furthermore, available genomic variation data and protein interaction interface information will be used to investigate whether known pathogenic mutations of NDDs are likely to disrupt the predicted brain-specific molecular mechanisms. Predicted mechanisms will be tested in vitro within the lab and with collaborators in neuronal cell models.
You will join a young, highly dynamic, and interdisciplinary research lab. You should ideally have basic expertise in programming and statistics as well as in molecular biology techniques and a strong interest in integrative, data-driven systems approaches to biology.
What we offer:
· Exciting, interdisciplinary projects in a fully 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 140 PhD students from 40 different countries
Requirements:
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!
We seek enthusiastic candidates with a special interest in the following topics:
· Ageing & Disease
· Bioinformatics & Computational Biology
· DNA Repair & Genome Stability
· Epigenetics & Nuclear Dynamics
· Gene Regulation & Evolution
· RNA Biology
Further requirements:
Master or equivalent
Interactive personality & good command of English
2 letters of reference
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 27 November 2020. Interviews will take place in Mainz on 25-27 January 2021 if the pandemic situation allows. Otherwise we will inform selected candidates in due time about an alternative online programme.
Starting date: 1 March 2021 – 1 September 2021