R&D: What does ZeClinics do?

ZeClinics laboratory R&D efforts are mainly divided in the development of three research platforms including a number of research areas.

Larvae zebrafish at ZeClinics

By Vincenzo Di Donato, Scientific Director at ZeClinics.

Vincenzo is an experienced researcher in Molecular Biology and Genetics. He obtained his Ph.D. in neuronews at the Curie in Paris where he contributed to the establishment of innovative CRISPR/Cas9-based tools in zebrafish. Since 2017, Vincenzo has been coordinating ZeClinics' Genetics Research area. Just recently, he has been appointed the Scientific Director of ZeClinics.

Areas of R&D at ZeClinics are distributed among Three Platforms: ZeGenesis, ZeEfficacy, and ZeTox

One might think that it is too ambitious for a single laboratory to exploit the zebrafish model to its fullest. But at ZeClinics we do our best by covering the most diverse areas of research, from genetics to toxicology, from CNS development to heart regeneration.

Happily, we are able to do so because we count on a growing team of zebrafish scientists experts, each of them specialized in a specific field of research. This allows us to cover that great number of research areas. Then, independent of the area, our work focuses on:

  • Services for third parties from the experimental design, project planning, execution to its completion.
  • A research and development program that allows us to continuously optimize existing tools, generate novel techniques to streamline zebrafish-based studies, and validate the biological translatability of the model, which is our greater goal.

These lab efforts are mainly divided into the development of three research platforms, ZeGenesis, ZeTox and ZeEfficacy (original naming is certainly not our finest skill!). For you to get to know us better, let’s have a look at them:

1. ZeGenesis:

Since the establishment of the first mutagenesis techniques by George Straisinger, father of zebrafish research, the world of zebrafish genetics has been revolutionized multiple times, but we always try to follow the pace.

At ZeClinics, we are interested in streamlining processes to study the effect of gene loss of function for disease modeling and target validation. The use of the CRISPR/Cas9 system and the multiple approaches that it offers are the core of our ZeGenesis area.

Our current efforts focus on two main goals:

  1. Achieving high gene disruption rates in F0 larvae for direct analysis of the effect of mutations on tissue development and function (Crispants);
  2. Implementation of knock-in approaches for integration of disease-associated SNPs into the zebrafish genome.

The results obtained during the last years are encouraging and helped us and our clients to speed up the discovery of relevant therapeutic targets and gain insights into pathogenic mechanisms underlying human disease.

2. ZeTox:

Although the zebrafish model has proven valuable for screening large libraries of different classes of molecules, there is still a big concern, mainly by the non-academic world, about the translatability of results from zebrafish to humans.

The effort of our toxicology platform is directed towards enhancing the validity of the zebrafish model for predicting chemical substance toxicity (in particular novel drugs and chemicals with a potential risk to humans).

Along this line, over the last years, we have performed comparative studies between zebrafish larvae and gold standard models for detection of developmental teratogenicity (rodents and humans) and cardiovascular toxicity (human-induced pluripotent Stem cell cardiomyocytes – hiPSC and clinical data) induced by compounds. Importantly, we found that zebrafish embryos display higher predictive performance than other models.

The aforementioned validation studies represent the basis and the strength of our ZeTox service portfolio, a high-throughput, translatable battery of toxicology assays that uses zebrafish at different developmental stages for the system safety assessment of novel drugs.

In order to achieve soon the approval of international test guidelines for toxicology testing, we are participating in a large number of international multi-laboratories initiatives.

3. ZeEfficacy:

All the zebrafish genetics or pharmacological disease models generated through the other platforms would not make sense without this last one. The ZeEfficacy area focuses its research efforts mainly in two fields:

3.1. Establishment of tools for high-throughput phenotyping of larval models

3.2. Development of novel assays/disease models for efficacy assessment of potential therapeutic compounds.

Throughout the years, always driven by a passion for automatization, we have optimized our experimental pipelines and are now able to perform an accurate and fully-automated phenotypic assessment of zebrafish larvae (mutants, transgenics, or treated with compounds of interest) in different fields, being the cardiovascular and neurobehavioral our stronger fields.

Meanwhile, we keep on broadening our expertise to tackle other heavy social burdens. To this end, we started implementing larval and adult models of non-alcoholic-fatty liver-diseaseAged Macular Degeneration, and Muscular diseases among others.

We hope this overview helped you to know a bit more about our activity. Now that you know more about us, would you like to tell us about your research?

As you may have understood, we are always open to collaborate and keep adding value to your, our zebrafish work.

Chemical toxicityCRISPR/Cas9Disease modelingdrug discoveryGene-editingHigh Throughput Screeningphenotypic screeningR&DZebrafish