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Post Doctoral Research Assistant - Engineering fully functional, integrated skeletal muscle

Faculty of Education & Sport

Fixed-term contract funded for a period of 36 months (start date January 2010)
37 hours per week

Engineering fully functional, integrated skeletal muscle

Institute of Sport and Physical Activity Research (ISPAR), Bedford
UCL Institute of Orthopaedics, Royal National Orthopaedic Hospital, Stanmore
UCL Institute of Neurology, National Hospital for Neurology and Neurosurgery, London (IoN)

An exciting opportunity has arisen following a recently awarded grant from the National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs). The project is part of a wider programme of work led by Professor Mark Lewis and Dr Vivek Mudera that has, over the past 10 plus years, sought to identify the ideal niche conditions for in vitro function of primary muscle precursor cells. This has led to the development of methodologies for the isolation, purification, characterisation and maintenance of such cultures. From these cultures, we have reported on pathways for successful proliferation, migration, fusion and maturation. In recent years, the influence of the mechanical three-dimensional environment has come to the fore and is the starting point for this project. Our group now has at its disposal 3D biomimetic models that show some of the physiological and biochemical features of skeletal muscle. In order to develop the use of these organoids for studies in exercise physiology, motorneuron disease pathogenesis, drug testing and orthopaedic research the inclusion of a neuronal input is required. In order to achieve this, collaboration with Professor Linda Greensmith has been developed. The currently funded project is to build on preliminary data that indicates that nerve-muscle contacts can be created using the three dimensional skeletal muscle constructs. Such a model would reduce the need for in vivo testing in animals.

Using such a system, several cultures can be established using muscle and motor neurons derived from individual animals, thereby decreasing the numbers of animals used. The successful applicant will therefore both developmental (fibrin matrix and electrical stimulation) and regenerative (collagen matrix and mechanical stimulation) 3D tissue engineered models of skeletal muscle to attempt to fulfil the following:

1) Engineer a 3D motor neuron interface.
2) Perform Quantitative Structural analysis of the 3D muscle-nerve constructs using confocal microscopy, TEM and SEM to precisely define the structural morphology
3) Determine, define and quantify the functional effects of NMBA on motor neuron stimulated muscle force production (in real time using the Culture Force monitor)
4) Determine pharmacology of the muscle end-plate
5) Engineer nerve-muscle co-cultures from muscle cells isolated from transgenic mouse models of ALS, eg SOD1 mice, to determine whether the disease can be recapitulated in vitro and define and test the limitations of this model
6) Establish the viability of human-rat chimaeric cultures.
The post will be based at ISPAR in Bedford but activity will occur between the three collaborating Institutes. For reference, Bedford and Stanmore are less than an hour apart by car (M1 Junction 13 to M1 Junction 5). All three sites are connected via the Midland Mainline (London St Pancras International, Elstree & Borehamwood and Bedford) – fastest journey times from London to Elstree & Borehamwood are 20 minutes and from London to Bedford are 35 minutes. This post will also involve a period of research (approx. 3 months) in the laboratories of our collaborator Dr Keith Baar, University of California, Davis, USA.

Potential applicants are encouraged to contact Mark Lewis (mark.lewis@ucl.ac.uk or tel: 01234 793359).

To apply for this position, please download an application form from our website by clicking the Apply Now button below or alternatively, you can contact Human Resources on the number listed within the 'View Contact Details' section below. Please quote the reference number and job title. CVs will only be accepted in addition to a fully completed application form.

Closing date: 19 November 2009