A Super Relaxed Journey in Japan – news from my MSCA GF project between EU and Japan

How important is the calcium diffusion in the sequential activation of the thick filament? I discussed about this topic in a previous post . With my collaborators at the Department of Biomedical Science s in Padova University, we are exploring this issue through a mathematical model based on experimental data on calcium signalling in the three main compartments of the muscle cells: sarcoplasmic reticulum, cytosol and mitoshondria. In fact, while usually neglected, we think that mithocondria may play an important role in the calcium distribution during activation, at least in skeletal muscle cells. Our work lead to an extensive review done with the priceless enormous contribution of Prof. Carlo Reggiani, just published in the Journal of General Physiology.  You can read it here , but our main conclusion is that the mitochondria may have an important role, and that this must be elucidated with further analyses.  From the point of view of the super relaxed state, and its activati...

 The first part of my project aims at collecting as much as possible (AKA "all") the current knowledge of the mechanosensing mechanism, or WHY and HOW the super-relaxed myosin heads decide to rise up and start the actomyosin cycle to produce force. Here, I report a striking result from Brunello and Fusi, at King's College of London, published in PNAS in march 2020.  The applied the X-ray diffraction technique to study the thick filament structure in cardiac muscle. Small angle XRay diffraction is one of the most used techniques to dynamically analyze the state of the thick filament, thanks to the different spacing that the myosin motors have in each state. The interpretation of the data is made through mathematical models of predicted X-ray diffractions from different populations. Despite it is necessarily based on some assumptions, its interpretation can be considered well established in the literature. I do not report here the beautiful pictures reported in the paper b...

  Let me introduce shortly the project.   The main reason why I am living in Japan now.   The super short story, is that a new state has been “recently” discovered in the striated muscle. A state which is stable in the   relaxed muscles , which was   hiding itself   because for many decades researchers were interested in the  active behavior of muscles . It’s obvious isn’t it? You want to know how muscle contract, not how the can stay relaxed!! Well, the current view is that this new state, called  SUPER-RELAXED STATE , can deeply influence the  active behavior  of muscles, especially of cardiac muscle, causing also serious diseases when it’s  equilibrium is perturbed . So, in this sense the super-relaxed state is pretty “active” or “genki” (げんき, or 元気) in Japanese. A 元気 super-relaxed state ! So! My Global Fellowship project aims at: (i) defining the theoretical bases of the recently discovered “mechanosensing” (MS) mechanism that a...

Probably, the best way to start this blog is... from the beginning. I arrived in Japan in September 2021 as the outgoing period of a Global Fellowship project which has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 886232 and here I will shortly describe the project aims. First, the Global Fellowship are grants "open to European nationals or long-term residents who wish to engage in R&I projects with organisations outside EU Member States" These fellowships require an outgoing phase of minimum 12 and maximum 24 months , as in my case, in a non-associated Third Country. For the reason outlined below, I chose JAPAN 🇯🇵 as hosting country . After the outgoing period there is a mandatory 12-month return phase to a host organisation based in an EU Member State which in my case is ITALY 🇮🇹. The hosting organizations are RIKEN in Japan, and Padova University in Italy. My p...