” …alleviate disuse atrophy and reloading injury, to allow for better muscle regrowth”

Serge Ducommun, Post-doctoral researcher

Most of us have probably seen videos of astronauts exercising in space, and we know that it is because our muscles deteriorate and become weaker when not being used. For this reason, astronauts will be using specially designed exercise machines trying to at least limit their muscle loss while in space. This muscle deterioration, called atrophy, also occurs on Earth, when people are bed-ridden for a period of time for example.

Just as important as preventing muscle atrophy is trying to understand what happens afterwards when the astronaut returns to Earth, or when the patient is able to leave the hospital bed again. Atrophied muscle is not used anymore to carry the load of the human body. Although it will quickly start to regrow, a process called hypertrophy, it will nonetheless be subjected to reloading injury during this process, with small tears in the muscles causing soreness and inflammation.

One of the projects in our laboratory is to better understand this chain of events: disuse atrophy, reloading injury and hypertrophy. To do this, we are using a mouse model of muscle unloading and reloading, where the mouse doesn’t use its hind legs for a couple of days and is then allowed to use them again normally afterwards. Using techniques such as RNA sequencing and mass spectrometry that allow us to look at sub-microscopic changes taking place inside the muscle cells, we are identifying genes and proteins that are involved in these events.

With this information, we hope to better be able to monitor how much muscle deteriorates and how well it can recover afterwards. This might pave the road for us to develop drugs and to prescribe specific exercises that could alleviate disuse atrophy and reloading injury, to allow for better muscle regrowth.

 

“…to understand complex biology underlying healthy muscle repair and identify what fails in muscle pathologies”

https://ruaslab.science/lab/team/jorcor
Jorge Correia, Post-doctoral researcher

Loss of muscle mass and function is commonly seen in patients with chronic inflammatory diseases and is the major clinical feature of various neuromuscular diseases, such as muscular dystrophies and myopathies.

To date, most neuromuscular diseases remain incurable and available therapies to extend life span and improve quality of life are limited. Remarkably, most mechanisms implicated in these pathologies largely overlap with mechanisms activated during healthy muscle regeneration. My research aims to understand the complex biology underlying healthy muscle repair and identify what fails in muscle pathologies.

There is much left to discover but our research already identified a previously unknown mechanism that coordinates how different cells communicate during muscle regeneration and that is aberrantly activated in muscular diseases. We are developing ways of manipulating this mechanism as potential treatments for neuromuscular diseases. We are also exploring how these approaches could be further used to improve muscle function during aging and in a variety of chronic diseases, such as diabetes and cancer. 

 

“…finish a marathon or eat all the delicious food while keeping a six-pack, I will be providing the means, not the judgement”

Igor Cervenka standing in front of a wall with green leaves
Igor Cervenka, Post-doctoral researcher

My main personal research interest revolves around various aspects of weight-lifting and resistance exercise. One reason is that I resent running with a passion, and extra ammo for arguments with running freaks might always come in handy. Unfortunately, due to the technical limitations of mice research, I am forced to confine these interventions to myself. Later in the lab, I at least try to recreate some of the isolated processes that happen during exercise, especially the increases in muscle size and function.

This might turn out to be useful since I am not getting any younger (and neither are you). Although my sporadic visits to the gym are sufficient to sustain my muscle needs so far, I can foresee that it will not always be the case. Google “sarcopenia” if you want to freak out about this. I am here to tell you that it is better to get prepared for when the time comes, throwing dumb-bells and knowledge at it would be a good start.

I have to admit that I also run a side hustle that is connected to endurance training. Nature didn’t want us to be naturally fit, we have to work hard for it whether we like it or not. But sometimes, we could all use a bit of a boost. It is a major nuisance that effects of exercise are so short-lived, what if a little bit of tweaking would help us achieve the same with less effort. Whether you use to finally finish a marathon or eat all the delicious food while keeping a six-pack, I will be providing the means, not the judgement.

 

“The answer might be hidden in what we call The Dark Side of the genome.”

Paolo Jannig in a green background on a sunny day
Paulo Jannig, Post-doctoral researcher

A wide range of diseases affects how well our muscles work. This has been related not only to poor quality of life due to muscle weakness but also to the fact that loss of muscle mass worsens the overall prognosis of almost any disease. It is also interesting to note that people respond differently to the same disease state, where some rapidly develop muscle atrophy, while others are able to maintain their muscles fairly intact even though the disease is still present. So, what determines these individual responses? The answer might be hidden in what we call “the Dark Side of the genome”. Indeed, the years following the completion of the Human Genome Project revealed that most of the common genetic mutations are not located in coding genes, those that carry the information required to build proteins, but actually in genomic regions whose function was unknown and usually referred as junk DNA. Nowadays, some of these regions are called “enhancers” and control when and in which cells a given coding gene (or group of genes) will be activated. Thus, my research aim is to shed some light on this part of our genome, trying to identify enhancers involved in the activation of genes during loss and gain of muscle mass. By doing this, we would be able to, for example, identify patients with high risk for developing muscle atrophy. This information could be used to optimize the disease treatment in a personalized fashion, curbing muscle loss and ultimately improving recovery and survival rates of conditions such as cancer, diabetes, spinal cord injury and others.

 

“However, part of this machinery is still unknown.”

Michele Azzolini, Post-doctoral researcher

Certain physiological (e.g. high-altitude training and high-intensity exercise) and pathological (e.g. strokes and cancer) situations lead to a considerable drop in cell oxygen content, which eventually allows for the stabilization and activation of the Hypoxia-inducible factor 1-alpha (HIF1a). HIF1a forms and drives a protein-machinery that adapt cell metabolism to low oxygen content. However, part of this machinery is still unknown. My research project aims to understand the molecular and metabolic adaptions of our cells to low oxygen conditions, with a special focus on folate metabolism. Our preliminary data point to unexpected enzymes in the folate pathway as a new component of the HIF1a machinery. Our current efforts aim to understand to what extent and in which situations HIF1a cross-talks with the folate pathway and, eventually, how we could intervene pharmacologically in these circumstances.

 

“better understand muscle performance and function in various circumstances, such as exercise or muscle disease”

 Duarte Ferreira
Duarte Ferreira, Senior Researcher – Lecturer

 

The aim of my project is to better understand how muscle mass and its functions are regulated in the presence of a specific protein, called LMCD1. Structurally, this protein has two different forms. The first form of LMCD1 protein regulates muscle contraction performance. I am interested in studying the effects of LMCD1 in more detail. By learning more about the role of this protein, we can better understand muscle performance and function in various circumstances, such as exercise or muscle disease.