PhD

ProgRET is a Marie Skłodowska-Curie Doctoral Network (2024-2027), offering 10 PhD positions. The objective of ProgRET is to train a new generation of vision researchers specialising in inherited retinal diseases (IRD).

The objective of ProgRET is to conduct advanced vision research that addresses the knowledge gaps to understanding, diagnosing and treating autosomal dominant inherited retinal disease (adIRD), using innovative approaches related to genomics, transcriptomics, epigenomics, multi-omics, bioinformatics, gene regulation, retinal stem cell models, organoids, aquatic animal disease models, and therapy development.

We will pursue the following specific research objectives: 1. To understand mechanisms of adIRD using retinal stem cell and aquatic animal models; 2. To advance diagnostics in adIRD using a single-molecule multi-omics framework; 3. To develop novel therapeutics for adIRD using RNA therapy and genome editing.

We are still recruiting for Project #9 (DC9):

DC9: Allele-specific, mutation-independent rescue of dominant negative acting IRD mutations by single gRNA-Cas variant genome editing

Supervisor: Dr. S. Kohl

Host institute: University of Tübingen, Germany

Secondments planned: Gulliver Biomed, Belgium; Institute for Neurosciences of Montpellier, France

Doctoral program: Mathematics-Natural Sciences at Eberhard Karls Universität Tübingen

Anticipated starting date: as soon as possible

Project description DC9@UT: Certain pathogenic variants in known inherited retinal disease related genes are known to cause autosomal dominant disease by gain-of-function pathomechanism. We anticipate to rescue the phenotype by specifically disrupting the aberrant allele via genome editing strategies. Specifically, we will focus on an allele-specific but mutation-independent design to overcome mutational heterogeneity. Within our research group we have identified frequent SNPs in these genes that are also commonly found heterozygously in the general population. PhD student DC9 will develop a cell-based reporter assay to unbiasedly screen for potent and specific gRNAs and Cas variants, and will effectively target such SNPs in cis with the respective mutation. DC9 will apply and further develop small and specific synthetic genome editing molecules that will be bioengineered to result in robust mutant allele-specific gene disruption, hereby leaving the wild-type allele of the gene intact. By shutting off the production of mutant protein, the project aims to rescue the disease phenotype in patient-derived cellular models and/or retinal organoids using clinically viable delivery tools (i.e. AAV particles).

How to apply:

To apply for one of these positions, submit to simone.dusseljee@radboudumc.nl a single pdf document containing:

• a detailed CV in EU format, including education, work experience, skills, dissertations, research interests, career objectives, and names and contact details of two referees, that can include the supervisor of the master thesis, willing to provide confidential letters of recommendation;

• a max. 1-page letter of motivation regarding the position(s) as well as the ProgRET network;

• a transcript of the master studies’ grades (including the overall grade and an explanation of the grading system) and the master’s thesis if available;

and indicate as TITLE your full name and DC9

Contactperson: Dr. Pietro De Angeli

Email: pietro.de-angeli@med.uni-tuebingen.de

DEADLINE: 06-26-2024

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