The Zammit Group
The Zammit group's core research aims to understanding the regulation of satellite cell function in both normal and diseased muscle. The functional unit of skeletal muscle is the myofibre: a giant syncytial cell maintained by hundreds of myonuclei. Growth, maintenance and repair of the post-mitotic myofibres is performed by satellite cells. These resident stem cells are located on the edge of muscle fibres, below the surrounding basal lamina.
Skeletal muscle is an archetypal adult stem cell model: maintenance and repair of functionally specialised post-mitotic cells is achieved by recruitment of undifferentiated precursors. Therefore, skeletal muscle provides an accessible model system with which to investigate adult stem cell control and function.
A satellite cell immunolabelled with M-Cadherin (red), in its niche on an isolated muscle fibre, where myonuclei are labelled in green
Research into satellite cell function is also relevant to understanding muscle diseases. Muscular dystrophies are all characterised by progressive skeletal muscle weakness and wasting, and have been mapped to at least 29 genetic loci. While muscular dystrophies vary in: age of onset; muscles affected and severity, the common factor is that the primary genetic defect ultimately results in muscle wasting, meaning that the homeostatic/regenerative process carried out by satellite cells is gradually compromised. By investigating the regulation of satellite cell function we can increase our understanding of why satellite cells initially maintain muscle function but then gradually fail in dystrophic conditions.
Theoretically, manipulation of the satellite cell pool in dystrophic muscle could both augment and prolong muscle function. This also has the advantage that it maintains a muscle environment still capable of responding to other forms of therapeutic intervention.
We work closely with, amongst others, Dr. Juliet Ellis (Randall Division), Dr. Jennifer Morgan (Institute of Child Health, UCL) and Dr. Frederic Relaix (Faculté de Médecine Pitié-Salpétrière, Paris).
We are grateful to the Medical Research Council, The Muscular Dystrophy Campaign, Association for International Cancer Research, the Association Française contre les Myopathies and The Wellcome Trust for supporting our research.
We are partners in OPTISTEM from the European Commission 7th Framework Programme-Health-2007-B (HEALTH-2007-1.4-6 - Grant agreement number: 223098) and BIODESIGN - Rational Bioactive Materials Design for Tissue Regeneration from the European Commission - FP7-NMP-2010-LARGE-4 - Grant number: 262948-2.