MUSCLE STRESS RELIEF contains seven (7) work-packages (WP), of which six (6) implement the scientific objectives, including research training of ESRs, while one (1) supports the research administration and consortium-wide research networking activities.
Experimental work took place both in Y1 and Y2 of the action and key experimental deliverables were achieved providing new evidence on mechanisms of stress factors interaction on muscle development, regeneration and contractility of skeletal muscles, including identification of targets for subsequent therapeutic interventions. Moreover great progress on identifying biomarkers and improving diagnostic tools has been achieved paving the way for innovation.
Summary of Consortium Achievements
The consortium, among other achievements, has:
• Established and operated the ‘Muscle Stress Relief network office’ and created and used the project’s logo and website
• Identified key genes within the injury-repair context which code for enzymes whose depletion leads to an inadequate muscle regeneration and are working to determine in vivo targeting patterns of those key genes
• Identified critical auto-phagosome activators brought about by mitochondrial dysfunction as well as determined key signalling and denervation mechanisms that lead to muscle wasting.
• Revealed molecular mechanisms underpinning skeletal muscle function under fatigue conditions and showed that renal disease induces appreciable skeletal muscle force depletions at the cellular level.
• Determined pathophysiological mechanisms underlying diaphragm weakening during mechanical ventilation.
• Achieved an advantageous method for the more accurate serological diagnosis of Myasthenia Gravis incl. a novel serological marker for cardiac injury.
• Screened small molecules with a potential to interfere with the identified key genes within the injury-repair context & identified those interfering with muscle stress sensing
• Characterised the role of a novel protein involved with the polarised fusion of muscle myoblasts and ultimately the formation of new muscle fibres
• Defined critical interaction domains in stress signalling in order to develop small molecules or other interference
• Identified novel regulators of autophagy that control muscle mass
• Revealed a strong involvement of oxidative stress in cardiovascular and striated tissue dysfunction
• identified a novel regulatory mechanism of titin-based passive tension, and set the stage to further test diaphragm rescue strategies
• Provided the first evidence that exercise doesn’t worsen myocardial stunning and showed exercise improving cardiovascular function in renal patients.
• Revealed a previously uncharacterized gene that controls longevity and proteostasis
• Identified AAV gene transfers interfering with muscle stress sensing and potential targets to prevent heart failure.
• Developed a very sensitive radioimmunoassay (RIA) for anti-titin antibodies and achieved its simplification for future routine use at the point of care.
• Optimised technology and methodology to characterise stress environments in disease states
• Provided support for improved SME marketing of antibodies diagnostic for muscle stress
• Delivered workshops and training events to ESR and ER in cutting-edge experimental myology methodologies and fostered networking within both academia and industry.
• Provided opportunities to ESRs to strengthen their career potential and supported their next career steps through mentoring and competencies training
In period 1 MUSCLE STRESS RELIEF researchers published > 8 peer-reviewed articles reporting progress in scientific objectives, and provided 5 workshops and 2 seminars to ERs and ESRs as well as dissemination (to the scientific community) and communication (to health professionals and the public) actions.
In period 2 a further 16 peer-reviewed articles were published and more work submitted, with achievement of scientific objectives. Additional workshops and seminars were provided, as well as dissemination and communication actions with a culmination in the final consortium conference in November 22-23, 2019, University of Thessaly. The conference theme was ‘The effect of chronic conditions on muscle biology and function’.
