The role of extracellular matrix receptors for stem cell function in
skeletal muscle
School: Biological Sciences
Supervisor(s)
Application Deadline: 30th November 2007
Description:
Satellite cells are the stem cells in adult skeletal muscle and lie
in their own niche separated from the muscle fiber by a basement
membrane. Under normal circumstances, satellite cells are quiescent,
but become activated upon muscle injury in the adult and contribute
to tissue regeneration and self-renew their own population. Satellite
stem cells are therefore believed to be a powerful tool for cell-
based therapies in muscle wasting diseases. However, our
understanding of the basic mechanisms that regulate satellite cells
behaviour is still rudimentary. Our laboratory has recently shown
that mice lacking integrin alpha 7 and dystrophin (DKO) have a
similar phenotype as Duchenne muscular dystrophy in human with
respect to the progression of the disease, tissues involved and
premature death post-puberty. Strikingly, a majority of muscle fibers
was lost after the first wave of degeneration. As integrin alpha 7
has also been shown to be expressed in satellite cells, the data
suggest that in the absence of integrin ¦Á7 and dystrophin muscle
regeneration is impaired. Yet, the underlying mechanisms remain to be
identified. The student will therefore test the hypothesis that in
the absence of integrin ¦Á7 and dystrophin satellite cell activation
and self-renewal is defective, applying molecular, genetic and
cellular technologies.
References:
Guo, C., Willem, M., Werner, A., Raivich, G., Emerson, M., Neyses, L.
and Mayer, U. (2006). Absence of alpha 7 integrin in dystrophin-
deficient mice causes a myopathy similar to Duchenne muscular
dystrophy. Hum. Mol. Genet., 15, 989-998.Nawrotzki, R., Willem, M.,
Miosge, N., Brinkmeier, H., and Mayer, U. (2003). Defective integrin
receptor switch in alpha 7-deficient muscular dystrophy. Hum. Mol.
Genet. 12, 483-495.Allikian, M.J.., Hack, A.A., Mewborn, S., Mayer,
U., and McNally, E.M. (2004). Genetic compensation for sarcoglycan
loss by integrin alpha 7 beta 1 in muscle. J. Cell Sci., 117, 3821-
3830.Mayer, U. (2003) Integrins, redundant or important players in
skeletal muscle?. J. Biol. Chem., 278, 14587-14590.
D.J. (2006) Muscle stem cells in development, regeneration and
disease. Genes Dev., 20, 1692-1708.
Research Areas: Cells and Tissues
Keywords: Pathology; Genetics; Cell Biology; Medical Science;
Clinical Science; Development; Molecular Biology; Zoology; Animal
Science
Funding Status: Funding available (Home/EU students)
Suitable first degree: Cell Biology; Developmental Biology; Genetics;
Molecular Biology; Biological Sciences; Natural Sciences
Contact: For informal enquiries about this position please contact
Prof Ulrike Mayer at u.mayer@uea.
Admissions Office at scipg@uea.ac.
How to Apply: Please download an application form from
http://www1.
Completed application forms should be sent to:
Faculty of Science Admissions
University of East Anglia
Norwich
NR4 7TJ
UK.
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