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Report

Teaser, summary, work performed and final results

Periodic Reporting for period 1 - 4DHeart (4D analysis of heart development and regeneration using advanced light microscopy)

Teaser

Summary

4Dheart is an innovation training project organized by researchers from academic and private sectors to achieve two key aims:

- Recruit talented students and train them
- Create inter-connected collaboration between academic and private sectors
- Start with implementation of the individual projects
The kickâ€“off meeting was held in Madrid between October 16th and 18th, 2017 with the attendance of all partners. Management boards and strategies for collaboration were established at that point. The recruited ESRs had the opportunity to present their individual projects to the consortium and discuss future collaborations. The Mid-Term Review Meeting took place on December 11th, 2018 at CNIC premises.
The recruited ESRs form a multidisciplinary and multinational team. We have students from Portugal, Rumania, Spain, and Italy with various backgrounds that include engineering, biology and computer science. During the lifetime of the project they will work together to approach bioimaging problems and open questions in cardiac biology. All recruited students have joined a PhD program at the corresponding university.
Following the essence of training ESRs on innovative research during the first year of the project the ESRs have attended several courses (the details can be found in Section 10 Training of this document).

Work performed

The kick- off meeting was held in Madrid at CNIC premises between October 16thand 18th of 2017. The meeting was attended by representatives of the partners involved in this ambitious project: Jochen Gehrig, from Ditabis, Germany; Florian Fahrbach, Leica, Germany; Julien Vermot, IGBMC, France; Willy Supatto, CNRS, France; Javier SÃ¡nchez, Philips, Spain; Peter Majer, Bitplane, Switzerland, and Michael Liebling, IDIAP, Switzerland. The meeting was attended by the followed freshly recruited ESRs: Eleonora Lupi, Tiago Fernando Ferreira da Silva, Laia Ortiz and Elena Remacha Motta. From the 18th to the 20th October, these four students also participated in the first of several training courses offered within the program. They learned about animal models in cardiovascular research, the use of databases and data management strategies to be implemented in their research projects from the very beginning as well as intellectual property and communication techniques.

Final results

5 of the 6 ESRs have been recruited between September 2016 and December 2016 and they have already started their research projects. Below you could find short decryption on short term scientific goals for each recruited ESR.
ESR 1 Laia Ortiz Quantitative analysis of outflow tract heart valve morphogenesis using light sheet time lapse microscopy
The project will be focused in the study of proepicardial (PE) formation in zebrafish. The main objective will be characterize the impact of Yap signaling in PE development using actin dynamics as a read out. We are also interested in studying the role of cilia in the process of Yap activation in the PE. To assess our questions, we aim to develop imaging protocols to perform live imaging of embryos using light sheet microscopy. (Figure 1)
ESR 2 Elena Remacha Quantification of cilia mechanodetection during pericardium development using optical tweezers
The cardiovascular system is vital to every vertebrate and is the first functional organ in the developing embryo. As a result, the heartbeats generate hemodynamic forces that physically stimulate the developing heart. The mechanisms underlying these phenomena are still poorly understood. The project will address this question by assessing the role of pericardial flow in the process of epicardium development by using newly developed imaging techniques like light sheet microscopy.
The cardiovascular system is vital to every vertebrate and is the first functional organ in the developing embryo. As a result, the heartbeats generate hemodynamic forces that physically stimulate the developing heart. The mechanisms underlying these phenomena are still poorly understood. The project will address this question by assessing the role of pericardial flow in the process of epicardium development by using newly developed imaging techniques like light sheet microscopy. (Figure 2)
ESR 3 Paul Stroe 3D and 3Dt Atlas of cardiac development in the zebrafish with a focus on the valves
The aim of the project is to generate a 3d and a 4D (3D+time) atlas to study the morphogenesis of the zebrafish heart development. The project will perform long term in vivo using multiview selective-plane illumination microscope and second harmonic generation. Furthermore, spatial and temporal registration tools will be implemented to integrate the multidimensional imaging data into a model of cardiac development. (Figure 3)
ESR 5 Eleonora Lupi High content screening assay for the identification of chemical compounds enhancing epicardium formation
- Optimization of embryo handling to enable standardized automated imaging of larval hearts, and implement imaging protocol to automatically acquire consistent low resolution (2D+t) and high-resolution (3D+t) datasets of larval hearts.
- Development of an automated analysis pipeline using data handling, image processing and data analysis tools and full integration of the developed toolset into the ACQUIFER screening platform.
- Improved screening capacity regards chemical compounds enhancing epicardium morphogenesis and testing the effect of 2- 3 drugs on cardiac regeneration using the zebrafish cryoinjury model. (Figure 4)
ESR 6 Tiago Silva In-vivo characterization of dynamic myocardial tissue changes in different mammals
Develop new MRI methods to be able to run advanced MRI sequences like T1, T2, T2* cardiac mapping, T1rho, 3D cine, 3D acquisition, and 4D flow in a 3T clinical scanner. Generate a MR method for small animalsâ€™ model on a clinical scanner, including 3D morphology and functional information, in order to depict heart shape and size at different time points in the regeneration process and build a 3D atlas of small animals hearts. (Figure 5)