Short Scientific Course 1: Biodiscovery with zebrafish

Location: KU Leuven, Belgium

Organising committee: Prof. Peter de Witte, Dr. Annellii Ny, Dr. Aleksandra Siekierska

All MarPipe Early Stage Researchers (ESRs) and Principal Investigators (PIs) had the chance to meet for the first time during a welcome dinner at the historical centre of Leuven, organised by the host laboratory of KU Leuven.

Day 1. Hoger Instituut Wijsbegeerte

The meeting started with a short introduction by the coordinator of the MarPipe Project, Professor. Donatella de Pascale. ESRs presented their PhD projects followed by questions and a short discussion. The aim of the meeting was for ESRs to communicate their individual research work in the framework of the MarPipe project.

In the afternoon, ESRs were given a guided tour of the historical centre of Leuven. Walking around the old streets of the town, visiting monuments that were restored after WWII and learning about the history of Leuven and Belgium were exciting moments of the ‘non-scientific’ activities for the ESRs.

Day 2. Campus Gasthuisberg ON2

ESRs were given an introduction to the drug discovery pipeline and the differences between phenotypic and targeted drug discovery. A session on the zebrafish as an in vivo model organism and the many advantages this animal model possesses (i.e. possibility of cost efficient high-throughput screening, potential to generate transgenic/CRISPR lines etc.) followed. ESRs had the chance to visit the aquatic facilities of the Laboratory Animal Centre at KU Leuven and learnt about the importance of development, husbandry and health of zebrafish. An overview of the safety assessment methodologies available for the zebrafish platform as well as their pros and cons were discussed. Particular emphasis was put on assays to evaluate general toxicity during development and organ specific toxicity (in liver, kidney, heart, central nervous system). Case studies where zebrafish were used as an in vivo model organism for research into tumour growth and tuberous sclerosis complex were presented. At the end of the day, a Postdoctoral Researcher who conducted her PhD as part of the PharmaSea Project (http://www.pharma-sea.eu/pharmasea/)presented her research on the zebrafish-based anti-seizure natural product drug discovery.

Day 3. Campus Gasthuisberg ON2

Time for some hands-on training for the MarPipe ESRs. At Station 1, ESRs had the opportunity to perform yolk injections on zebrafish embryos. Students were trained in all the steps of the microinjection technique from pulling needles and manipulating the injector to performing the injections and observing the results using a fluorescent microscope. At Station 2, ESRs learned about the spawning technique while they were trained in recognizing male or female zebrafish and collecting them in special mating tanks. Zebrafish embryos and larvae were observed under the microscope and ESRs were tested in identifying different developmental stages. Moreover, ESRs evaluated the effects of organ specific toxicity in liver, kidney and vessels, observing transgenic reporter lines of zebrafish larvae. At Station 3, ESRs were given the opportunity to perform behavioural analysis on zebrafish larvae (locomotion tracking) and local field potential measurements (EEG).

As a result of the first Short Scientific Course, all MarPipe ESRs became aware of the added value that zebrafish as a vertebrate model with high-throughput capacity can provide in evaluating the safety aspect of novel bioactive hit compounds of marine origin. The training equipped ESRs with the proper skills to conduct developmental and organ safety assays and to critically evaluate the application and use of such methods, their advantages and their limitations.

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