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Report

Teaser, summary, work performed and final results

Periodic Reporting for period 3 - AngioGenesHD (Epistasis analysis of angiogenes with high cellular definition)

Teaser

Summary

Our project main goal was to understand angiogenesis with high genetic and cellular definition. Angiogenesis or the formation of new vessels from pre-existing vessels, is induced by growing tissues that need to be perfused with oxygen and nutrient rich blood. This process is very active in cancer, and its inhibition significantly reduces tumor growth. In cardiovascular ischemia, there is also the need of regulating blood vessel physiology and growth. However, our knowledge of the genetic and cellular mechanisms of vascular growth is limited by the currently available genetic and imaging tools. With this in mind we developed new genetic and imaging methods to understand the function of genes during angiogenesis with much higher temporal and cellular resolution. In doing this, we decided to make the technology open-source and adaptable to the study of any gene function, in any cell type, and model organism. This allowed us to develop cutting edge-technology of broad interest and at the same time answer biological questions in the angiogenesis and vascular biology fields that could not be answered before. For the next half of the project we will continue to develop and refine this genetic technology, and will make use of it to get a deeper insight into the biology of blood vessels, during organ development and in disease. The final goal is to identify new mechanisms that can be used to manipulate vascular growth in cancer or cardiovascular disease.

Work performed

Since the start of the ERC project, we expanded and consolidated our research team. We also achieved important technical and scientific milestones. Some of those were published in Cell (Pontes-Quero et al., 2017) and others are now submitted and in revision before publication. These form the seed of future project developments in the group. Some of the findings will be further investigated in the next project period and we are also considering their exploitation. The results achieved were disseminated in international research conferences, scientific articles publication and local/international press releases.

Final results

Standard gene function analysis approaches, require comparison between cells present in separate control and mutant animals, having normally one gene mutated at a time. We developed new genetic methods that allow us to study the combinatorial function of up to 6 genes in up to 15 different cell types, occurring in the same tissue of the same animal. This significantly increases the speed and cellular resolution of gene function analysis. Improved methods for studying gene function will allow researchers to increase knowledge about how our genes operate in the multiple cell types that make up our bodies and understand gene interaction networks and their regulatory hierarchies. This knowledge, moreover, is crucial for the design of efficient therapeutic strategies to modify or correct genetic activity in disease.