Establishing a conditional immortalization system to be used in patient -derived myoblasts for therapeutic evaluation studies
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NESCI would be interested in funding / studentship opportunities for the following proposal.
NESCI are interested in industrial partners who may like to collaborate in one of these fields (for a CASE studentship or other awards), or in anyone who is interested in these areas of research (including other academic groups). For further details, please contact Helen Clamp from NESCI.
Project: Establishing a conditional immortalization system to be used in patient -derived myoblasts for therapeutic evaluation studies
Lead: Professor Hanns Lochmüller
Studies in musculoskeletal disorders are mainly carried out in mouse models and established mouse or rat muscle cell lines. When analysing new drugs or treatment strategies it would be beneficial to be able to bring this testing to patient level, since the effects seen in mice cannot be translated directly into humans. Myoblasts, the skeletal muscle stem cells hold a great therapeutic research potential. However, the use of these cells is hampered by poor growth and early senescence of these cells in culture. This project is therefore to establish a system to conditionally immortalize these human myoblasts.
The student will derive myoblast cultures from DMD and LGMD2B patients, and healthy control subjects. These cells will then be transduced with a construct containing a tetracycline-inducible promoter system using lentiviral vectors. Different cell cycle regulators such as Cdk’s or SV40 large T-antigen in combination with telomerase will be tested as potential new constructs. This is necessary since telomerase alone fails to induce immortalization of primary myoblasts. Once immortalized cell lines have been established these will be used for novel therapeutic research including ongoing drug trials currently undertaken in mice and human fibroblast cultures.
