Determine how disruption of Tm5NM1 leads to programed cell death

Determine how disruption of Tm5NM1 leads to programed cell death

Institute: University of NSW
Recipient: Professor Peter Gunning
Funding: $450,000 July 2010 to June 2015

The actin cytoskeleton, due to its role in tumour cell survival, is a highly desirable chemotherapeutic target, yet attempts to exploit it have been unsuccessful due to respiratory and cardiotoxicity.

The Gunning laboratory team want to determine how the disruption of Tm5NM1 containing actin filaments leads to programed cell death in tumour cells.

To date, the Gunning group have shown that tropomyosin is an integral component of the actin cytoskeleton and defines functionally distinct populations of actin filaments in non-muscle cells. Further to this, tumour cells express a specific repertoire of tropomyosins relying predominantly on the low molecular weight cytoskeletal tropomyosin, Tm5NM1.
 
The aim of this project is to characterise the mechanism by which disruption of the actin cytoskeleton by the group’s lead anti-tropomyosin compound, TR100, in neuroblastoma cells instigates cell death. Understanding this will provide insight into further points of vulnerability in this biological system leading to the potential for developing new anti-cancer targets.
 
Further, targeting anti-tropomyosin compounds in combination with existing chemotherapeutics may show to improve tumour sensitivity and when translated to the clinic reduce toxicity.