During the PhD period carried out in the laboratory of Prof. Paolo Bonaldo, I had the opportunity to work with an interesting model organism, the zebrafish. I published my first work (you can download it at this link) in which it characterizes the expression of Collagen VI in the different tissues of the fish model.
This small “laboratory fish” has innumerable advantages, such as, for example, complete transparency in the embryonic age, which allows the development of the various organs and tissues to be monitored much more easily than in the mouse.
I took advantage of these resources to thoroughly study the molecular mechanisms in which Collagen VI (COL6) plays a critical role. Initially I precisely identified the expression of COL6 and its deposition in the extracellular matrix at different stages of embryonic and postnatal development both in skeletal muscles and in different organs. Subsequently I focused on the study of a genetically modified zebrafish, which we produced using the new “genome editing” technology and unable to produce COL6 (Zebrafish COL6 null). I was able to highlight how this model organism has neuromuscular defects comparable to those observed in the knockout mouse, effectively electing it as an excellent model for the study of COL6 deficiency pathologies and large-scale drug screening and the study of targeted therapeutic approaches .
Furthermore, using different models of transgenic zebrafish called reporters because they are capable of expressing specific fluorescent proteins in certain tissues, I was able to identify that the absence of COL6 causes characteristic alterations of a new and specific intracellular signaling pathway during development and growth of the organism. This will be the starting point for my next research project which will have the ambitious goal of identifying the “molecular bridge” between COL6, present outside the cell, and the cellular defects widely studied and described so far.
The COL6 null zebrafish therefore represents an extremely useful and promising model, which will allow not only to shed new light on the molecular mechanisms underlying COL6 deficiency pathologies, but also to test possible therapies. In fact, the zebrafish is the vertebrate model organism of choice for large-scale screening of potential drugs.
I will continue, together with my colleagues, to work daily with perseverance and enthusiasm, convinced that step by step we can arrive at an increasingly complete understanding and effective treatment of COL6 deficiency pathologies.
A warm greeting to the members and supporters of the Col6 Italia ONLUS association,
Valentina Tonelotto