Two EPFL scientists win grants to help advancing the 3Rs

The 3Rs principles (replacement, reduction and refinement), shared by a large majority of scientists worldwide, aim to replace animal testing with alternative experimental approaches, reduce the number of animals used to the minimum necessary, and optimize experiments to avoid exposing animals to unnecessary or disproportionate stress.

In this context, the National Research Program "Advancing 3Rs - Animals, Research and Society" (NRP79) set up by the Swiss National Science Foundation, aims to promote innovative ideas and constructive approaches for solving problems regarding animal experiments and their legitimacy. This NRP, with a budget of 20 million francs, unveiled the list of the first 23 selected research projects on June 10, including two projects by EPFL scientists.

Refine the regeneration and development studies

Can Aztekin, an ELISIR scholar who heads the Laboratory of structural regeneration at the Swiss Institute for Experimental Cancer Research (ISREC), was awarded a grant for a multi-part project. The first part aims to study the regeneration of tadpole limbs in a Petri dish, without using a living animal. "We want to understand how and why certain animals, such as tadpoles, are able to regrow their limbs, so that we can one day, maybe, transfer this ability to humans. To do this, we have to use animals, because there is no other simplified system. This is a problem because we have to do limb amputations in vivo, which presumably causes pain and fear. This is where there is a huge potential for refinement," explains the scientist. He and his team will harvest the animal's tissue ex vivo and then study its growth in vitro, since the regeneration of the limb continues even after it is removed from the animal's body.

The second part of the project will consist in trying to better understand the development of the limbs, using stem cells, again in a Petri dish. In addition to replacing the use of animals, the scientific benefit of both parts of the project is also certain, as these models will allow the study of many aspects of development and regeneration that cannot be observed on a whole animal with a microscope. The project, funded with CHF 973,304, will last 48 months.

Reduce the number of used embryos

Alexandre Mayran, a post-doctoral researcher in ISREC’s Laboratory of developmental genomics, also received support from the NRP79 for a three part project to tackle several limitations to the use of in vitro pseudo-embryos."I looked into limitations that can prevent some scientists from using these models, why the mouse model is still used for the majority of developmental biology studies. This is the case for the study of small DNA sequences, enhancers, which regulate gene expression during development. Currently, to test and identify these sequences, they are often injected into mouse embryos at the early stage, in order to study where the injected DNA will be expressed in an embryo. That requires a lot of embryos, and a lot of surrogate mothers."

The researcher, whose host laboratory has drastically reduced the use of animals in recent years, will try to prove that patterns of gene expression already observed in vivo can be reproduced with pseudo-embryos, and then use them to test new ehancer regions. He also proposes to generate a reference atlas of existing in vitro models of embryos to allow researchers to easily identify the most appropriate model for their studies, and to offer a methodological framework to screen culture conditions that can lead to the emergence of embryonic cell types normally absent in pseudo-embryos. It is clear that these tools will not allow a complete replacement of animal experimentation, as pseudo-embryos are very basic and do not have the complexity of a whole organism, but they can replace parts of developmental studies and even accelerate research projects. This project, funded with CHF 815,096, will last 30 months.