Scheme: Newton International Fellowships
Organisation: Imperial College London
Dates: Jan 2010-Jan 2012
Summary: Heart diseases represent a significant contribution to premature death in the world. When the pumping power of the heart fails to meet the demands of other organs, the heart reaches the stage of breakdown and this is called heart failure. As a first consequence of damage, the heart will increase in size to compensate, but if this persists the deterioration and eventually the death of the heart result. Presently, the system with greatest proven capability to produce contracting cardiomyocytes is the human embryonic stem cell (hESC). To be able to produce cardiomyocytes from hESC, and to allow them to develop the adult phenotype, it is important to understand factors involved in cardiomyocyte differentiation and maturation. Normally any process that involves cell growth, death involves the transport of particular proteins from the cytoplasm of the cell to the nucleus, a process called nuclear protein import (NPI). Signalling proteins must enter the nucleus of any cell to allow the cell to create new proteins to meet the demands of its environment. However, little is known about NPI in hESC or hESC-derived cardiomyocytes (hESC-CM). I am using microinjection techniques to introduce a fluorescent import substrate to monitor NPI import rate. hESC-CM will be compared with adult ventricular myocytes from non-failing human heart, as well as those from failing human heart where the foetal gene program is reactivated. These studies will elucidate the role of NPI in hESC-CM differentiation and maturation, and potentially allow manipulation of these processes to improve the generation of cardiomyocytes for cardiac repair.
This project has a clinical relevance because understanding how to control the production of cardiomyocytes from hESC is important in treating heart diseases. This project has also a commercial impact in that factors will be identified for directed differentiation of hESC to cardiomyocytes by controlling NPI.