High throughput (HTP) genetic material screening for efficient direct reprogramming
Cell and tissue engineering, health, HTP screening, regenerative medicine, cellular reprogramming, cardiac tissue
Advancements in our ability to reprogram somatic cells from one cell type into another through the delivery of a defined set of factors or genetic material have led to a recent breakthrough in terms of reprogramming cardiac fibroblast cells into cardiomyocytes, in mice (in vitro and in vivo) and most recently, human cells (in vitro). These exciting discoveries offer significant potential in the future to repair damaged heart tissue post an acute myocardial infarct (AMI). However, the realisation of this potential is at present limited by 1.) the current use of delivery vehicles that are unable to be clinically translated (such a lentiviruses), and 2.) by the lack of capacity to rapidly screen genetic material for optimised and efficient direct reprogramming outcomes (current efficiencies are around 20%).
This project will address the second limitation to this becoming a therapeutic option for heart attack victims, through the use of a recently developed microfluidic cell-based device platform that enables high throughput screening of soluble factors and high content analysis of their impacts on cell behaviours. This project will screen a panel of genetic material factors and nanoparticle delivery vehicles, in terms of their efficacy in direct reprogramming of adult mouse heart cells and thereafter, human (iPSC-derived) heart cells, leading to the development of optimal factor formulations for efficient and targeted direct reprogramming for heart tissue repair. This project will be performed in collaboration with Associate Professor Ernst Wolvetang (AIBN) and Dr Enzo Porrello (School of Biomedical Sciences).
|Lead investigator||Professor Justin Cooper-White
|Research group||Cooper-White Group|