Wednesday, 18 September 2013

Hugh Huxley & the sliding filament theory

Hugh Huxley (25.2.1924-25.7.2013) was one of the many great Huxleys in British science. As a physicist he made major contributions towards the development of the sliding filament theory. Here is a great video where he described his path of discovery:

Monday, 16 September 2013

Satellite cells on the move

Roby Urcia, who is the postdoc on our Hippo MRC project, is currently working long hours to collect large numbers of activated satellite cells (myoblasts) for an experiment. Here is a great photo from today showing how satellite cells migrate from their mothership (muscle fibre) into the culture dish.
So what are satellite cells? Satellite cells are the resident stem cells of skeletal muscle and essential for muscle repair. They are wedged in-between the membrane of the muscle fibre (one fibre can be seen) and a mesh of stringy proteins which is termed the basal lamina. In normal, adult muscle they are quiescent but after injury or resistance exercise incompletely understood signals make them become activated and divide. Later on they fuse together to form new muscle fibres or repair existing, damaged fibres. In the above image a muscle fibre with the resident satellite cells has been isolated by Roby. In the medium used the cells divide extensively and also migrate onto the plastic of the Petri dish. There are still many things we don't know: how do satellite cell become activated? What signals guide them towards an injury site? What makes them switch from cell division to repair? We believe that the Hippo pathway is part of the answer but we hope to learn to better control their behaviour for example to improve their muscle maintenance in old muscle or to use them or similar cells for the treatment of muscular dystrophy. 

Finally, thanks for Prof Pete Zammit at King's College for showing us how to perform satellite cell isolations. Without his skills and generous support we would be still very close to square one!

Monday, 9 September 2013

BASES conference at UCLAN; signal transduction theory of adaptation

I am just back from the BASES conference which was held at the University of Central Lancashire from the 3-5th of September. The conference was very enjoyable because it was organised very well by Steve Atkins, his team & BASES and also I met a lot of former colleagues and students. My talk was entitled 'Molecular Exercise Physiology. Using molecular biology to answer key questions in sport and exercise science'. As the audience was broad (physiologists, psychologists, biomechanists, practioners) I tried to avoid the jargon and pathway diagramme trap and instead tried to explain the relevance, practical applications and focus on eye opening results and it seemed to work.

One of my topics was to make a case for the signal transduction theory of adaptation. It is illustrated in Figure 1 and explained below.

Figure 1. Schematical drawing depicting a general model that explains adaptation to exercise.

'How do we adapt to exercise?' is a key question for all exercise physiologists. The continental European sport science school has for a long time used the Yakovlev 'supercompensation' or 'overcompensation' hypothesis not only to describe the time course of the glycogen concentration before, during and after exercise (yes, it overshoots) but also tried to use it as a general explanation for adaptation to exercise. However, the latter has many flaws and its use to generally explain adaptation to exercise is not supported by experimental data. In contrast, UK-based training scientists and practicioners frequently use the principles of training as pseudo-mechanisms but I frequently find them trivial (who would have thought that organs need to be overloaded to trigger adaptations?) and struggle to see practical applications.

So for these reasons I argue that we should teach the signal transduction hypothesis of adaptation as illustrated in Figure 1. It is supported by a large amount of experimental data and helps students, coaches and athletes to understand how exercise changes cells and organs. Here is how it works (see Figure 1). (1) Sensor proteins (SE) sense, similar to our eyes, ears and muscle spindles, signals associate with exercise. Such signals in muscle fibres are calcium (sensed by calmodulin), oxygen (sensed by the HIF-system), AMP (sensed by AMPK), glycogen (sensed by AMPK) and mechanical signals (sensed by an unknown sensor and activates mTOR). These signals are then computed by signalling proteins (SP) which for signal transduction pathways or networks. These networks are comparable to the brain. The signalling proteins frequently phosphorylate or dephosphorylate each other but there are many other forms of signalling. (2) Downstream are effector proteins which regulate cellular changes that together are the adaptation. Transcription factors (TF) are an important class of effector proteins as they regulate the switching on and off of genes (transcription). (3) Especially after resistance exercise translation/protein synthesis is activated by translational regulators. Other effector proteins regulate the cell cycle or cell death.

Of the many talks of BASES I have most enjoyed the talk by James Morton, Liverpool John Moores. James has shown that training with low glycogen can increase adaptation and he has linked this to AMPK. His research bridges from molecular mechanisms (e.g. the glycogen binding domain of AMPK) to practical applications and this is a very good example of how effective Molecular Exercise Physiology can be.

Finally, if you are interested in the slides of the BASES presentation then just e-mail me (

Monday, 2 September 2013

PGC-1: a gene that regulates both adaptation to endurance and resistance exercise?

Today I am off to the BASES conference at the University of Central Lancashire which is organised by Steve Atkins and his team. My talk is focussed on Molecular Exercise Physiology.

Related to this is the relatively recent discovery by Jorge Ruas et al. that a PGC-1alpha isoform regulates hypertrophy. The paper has been published in Cell:

Jorge Ruas has presented this information at a conference and the slides and Jorge's talk are on this website:

Welcome to the Myoblog!

Welcome to Myoblog, my new blog. The focus of this blog are three topics:

1) Molecular Exercise Physiology
2) Skeletal muscle (myology)
3) Hippo pathway

In relation to these three topics I hope to achieve several things:
First, I plan to provide teaching materials and give updates on Molecular Exercise Physiology. Together with Neil Spurway I had written a book entitled 'Genetics and Molecular Biology of Muscle Adaptation': Also I have just submitted a book entitled 'Molecular Exercise Physiology. An Introduction' which should be published in 2014. So I will use this book to update on the book and also highlight papers that we have overlooked or that are published in the meantime. Also I plan to comment on my experience of teaching molecular exercise physiology to students.

Second, we plan to update on our research on the Hippo pathway in skeletal muscle. This is a major signal transduction pathway which regulates satellite cells (Judson et al. Journal of Cell Science 2012) and probably much more.

Third, I plan to add photos and protocols of methods that we use and wish to explain them. Having started as a human-focussed exercise physiologist, I spent much of my career looking for such information.

Fourth, I plan to update on conferences and meetings such as the London Myology and other muscle meetings, Hippo pathway meetings, the annual BASES conference and the Physiologogical conference meetings.

Feel free to e-mail me if under if you have relevant information.

At the end a simple stain of necrotic fibres using just an anti-mouse secondary antibody.
Figure 1. X5 image of a tibialis anterior mouse muscle stian for necrotic fibres by using an anti-mouse secondary antibody. Green-stained fibres are assumed to be necrotic.