Hosting researchers and contributing to their career development
Including the Radboud zebrafish facility as infrastructure for experimentation in grant applications is of great asset. The combination of a good research applicant’s CV with relevant infrastructure in project proposals is key to succeed with prestigious grant applications. As an example, the Radboud zebrafish facility was included as a host facility for experimentation in the grant proposal of dr. Francisco J. Arjona Madueño. This resulted in the awarding of a prestigious and competitive 2-year grant from the biomedical Foundation “Ramón Areces” (Spain). This grant allowed the development of a project that served as the basis for new collaborations (e.g. with the Erasmus University Medical Center, Rotterdam). The Radboud Zebrafish Platform provided supervision and guidance for the procedures that were carried out. Several members of the Platform were involved as supervisors of the work (dr. Peter H.M. Klaren, department of Animal Ecology and Physiology) and as co-researchers (dr. Erik de Vrieze, department of Otorhinolaryngology).
The awarded project studied the mechanisms by which thyroid hormones traverse cell membranes in zebrafish, and established a model for the Allan-Herndon-Dudley syndrome. The main findings of this project were:
- Thyroid hormones, despite their lipophilic nature, cross the cell membranes of zebrafish through thyroid hormone membrane transporters. This finding constituted the first direct evidence for this membrane transport mechanism in fish. One of the zebrafish thyroid hormone transporters identified was discovered to be the ortholog of the human transporter MCT8 (Endocrinology 152(12): 5065-5073, 2011).
- Loss of MCT8 function results in severely disrupted early development in zebrafish. As a result, zebrafish cannot move properly. In humans, loss-of-function mutations in MCT8 cause the Allan-Herndon-Dudley syndrome, where patients have developmental malformations and locomotor disabilities. Interestingly, loss of MCT8 function in mouse is not symptomatic. Therefore, the project with the Radboud Zebrafish Platform established a prominent pre-clinical model for the study of the Allan-Herndon-Dudley syndrome (Endocrinology 155(6): 2320-2330, 2014).
As shown by confocal microscopy at the Radboud zebrafish facility, zebrafish with impaired MCT8 function (B) displayed severe malformations compared with wild-type zebrafish (A). These images were used by the journal Endocrinology for the cover of issue 6 in volume 155.