
Inherited retinal diseases are an important causes of blindness. Currently, various types of genetic therapy are being developed that either correct the genetic defect, such as viral gene delivery or CRISPR/Cas9-mediated gene editing, or that redirect splicing during mRNA maturation, leading to translation of functional proteins. Despite considerable progress that has demonstrated the feasibility of these approaches, more research is needed to make these therapies more effective, and more broadly available for patients. On the one hand, delivery of gene therapies into retinal cells is still ineffective, on the other hand, some genetic defects require simultaneous delivery of several pieces of genetic material. This project will address both of these challenges.
For targeting new interventions to the retina, we want to generate cell-specific binding proteins through AI-based protein structure prediction. Designed proteins will be recombinantly expressed and tested for binding to retinal cells. Oligonucleotides will either be chemically linked or packaged into nanoparticles. The methodologies to be employed include tissue culture, retinal organoid models, confocal fluorescence microscopy, tissue-on-a-chip systems, AI-based protein modeling, protein expression and purification, nanoparticle formulation and chemical conjugation strategies.
Your main tasks are:
You will be embedded in two research groups, that of Prof. dr. Rob Collin (Department of Human Genetics) and that of Prof. dr. Roland Brock (Department of Medical Biosciences).
This PhD project is integrated in and financed by a large national consortium, Lifelong VISION, a Gravitation project funded by the Dutch Ministry of Education, Culture and Science (2024- 2033), that aims to develop new treatments against blindness. The Lifelong VISION program is developing a new generation of treatment strategies to prevent blindness: genetic therapies, treatments that target the disease pathways, and cell therapies. State of the art cell and animal models will be developed to test these new therapies in vitro and in vivo. The suitability of each patient group, and the optimal timing for therapeutic intervention is predicted using artificial intelligence, so that the right patient receives the right treatment at the right time. The innovative technologies and strategies developed for eye diseases within our project may serve as blueprints for other diseases and organs.
Ten research institutions participate in the Lifelong Vision project (led by prof. dr. Caroline Klaver), namely: Radboudumc, Erasmus MC, Amsterdam UMC, University of Twente, Hubrecht Institute, Eindhoven University of Technology, University of Amsterdam, Utrecht University, Tilburg University, and the Netherlands Institute for Neuroscience.
As a result, you will be exposed to a broad multidisciplinary environment, both intramurally and (inter)nationally.
Our ideal candidtate should have a background in Biomedical Sciences and/or Molecular Life Sciences, and be eager to take a pioneering role in AI-based protein engineering in the groups. Since the project involves the collaboration of two departments, you should be able to take initiative, communicate proactively and take full ownership of the project. Prior experience in tissue culture, microscopy, protein structure are considered a strength.
We are recruiting for this position ourselves. Unsolicited marketing is not appreciated, but do feel free to share the vacancy in your network!
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