Project title: Analysis of a Novel Actin Nucleating Machinery regulating Membrane trafficking

Project supervisors: Dr Anne-Gaelle Borycki (BMS)

Application deadline: Friday 14 December 2012.

Project description:

The extra-cellular matrix plays important roles in many aspects of embryonic development and in the adult by controlling cell behaviour such as proliferation, migration and differentiation. A specialised extra-cellular matrix structure called the basement membrane overlies the muscle fibre and contributes to its integrity and function. Mutations in components of this basement membrane are associated with congenital muscular dystrophy in humans. However, the addition of a specific Laminin, Laminin-111, can rescue the dystrophic phenotype in mouse models of congenital muscular dystrophy. Thus, Laminins and the basement membrane have critical roles in the regeneration of skeletal muscles.

The aim of this project is to characterise further the role of Laminins and the basement membrane using a combination of approaches in the zebrafish and mouse. The findings generated from this study will help us understanding certain muscular dystrophies caused by the degradation of the extra-cellular matrix surrounding muscle fibres, and may provide a framework for future studies to identify novel therapeutic approaches to congenital muscular dystrophies.

Techniques to be used: the project will use a combination of molecular and cellular biology approaches to further characterise the Laminins and basement membrane components essential for skeletal muscle regeneration. The project will benefit from the availability of genetic mutants in zebrafish and mouse that affect either components of the basement membrane or that are models for muscular dystrophies.

References:

• Claire Anderson, Sólveig Thorsteinsdóttir, Anne-Gaëlle Borycki. 2009.
  Sonic hedgehog-dependent synthesis of Laminin Alpha-1 controls basement membrane assembly in the myotome.
  Development, 136(20):3495-504.

Contact details:

Dr Anne-Gaelle Borycki

Email: a.g.borycki@sheffield.ac.uk

Web: http://www.sheffield.ac.uk/bms/research/borycki