C2D2 research 1b - Components of a skeletal muscle z-disc mechanosensor: do they contribute to the age related decline of muscle function in humans?

Project: Other projectOther internal award

Project participant(s)

Department / unit(s)

Layman's description

Muscle wasting is a known morbidity factor in many clinical or behavioural conditions involving chronic muscle paralysis and there are no effective countermeasures to prevent it. This project aims to start to identify the genetic elements of the molecular sensors which are involved in converting mechanical signals into biochemical ones and allowing skeletal muscles to sense loads. A secondary part of the project will be to measure the activity of genes that participate in these mechanosensors in young and old muscles, both in human and mice. This is in order to test the hypothesisis that one reason behind the inexorable decline of muscle power with age is that muscles become progressively less efficient at sensing and adapting to loads, because the mechanosensor complex changes over time.

Key findings

FINDINGS/RESULTS

The most significant finding is that overexpression of the z-disc protein KY in adult skeletal muscle increases the fibre diameter significantly. Thus, KY is sufficient to generate a hypertrophic response in the absence of overload stimulation.

Abstract selected for oral presentation for the 42nd European Muscle Conference.


COLLABORATIONS

1) Dr Elen Miyabara, Univesity of Sao Paolo

(BBSRC grant submitted involving a Brazil-UK partnership)

2) Dr Katja Gemlich

(BHF, PhD application submitted)


STAFF

PostDoc Laura Faas, 8 months.

COMMERCIALISATION/TRANSLATION

CASE studentship submitted with Dr David Bunka (Aptamers Solutions) using information generated from C2D2 grant (unsuccessful).

APPLICATIONS SUBMITTED

BBSRC - Brazil (FAPESP)
The role of the z-disc in muscle maintenance, regeneration, atrophy and hypertrophy
Gonzalo Blanco, Principal Investigator applicant
START 1/09/13 END 31/08/16
Total application£406,043.00 (unsuccessful)

MRC CASE studentship
1/10/2014 (unsuccessful)

BBSRC Studentship Mechanistic Biology
1/10/2013-30/09/17
£93,471 (awarded)

BBSRC Studentship Mechanistic Biology
1/10/2015-30/09/19
£93,471 (awarded)

BBSRC Tools and Resources
1/9/2014 (Unsuccessful)

ARTICLES AWARDED
Tugba Can, Laura Faas ,David A Ashford, Adam Dowle, Jerry Thomas, Peter O'Toole and Gonzalo Blanco, Proteomic analysis of laser capture microscopy purified myotendinous junction regions from muscle sections. Proteome Science 2014, 12:25 doi:10.1186/1477-5956-12-25.

Elliot J. Jokl and Gonzalo Blanco. Proteo-static: disrupted autophagy undermines skeletal muscle integrity. Autophagy, submitted.



StatusFinished
Effective start/end date1/07/1231/03/13

Research outputs

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