Novel role for Akt1 activation/translocation in mitochondria as regulator of hES cells
The main objective of the CIRM Basic Biology Awards II is to provide funding for cutting-edge stem cell research and to tackle significant unresolved issues pertinent to understanding the biology of human embryonic stem cells and the control of stem cell fate. Our laboratory recently discovered that we can modulate the expression of genes that regulates cell fate by activating a key factor (Akt) in the power plant (mitochondria) of human embryonic stem cells. This is a novel mechanism that has not been described in the human embryonic stem cells. Potential ability to adjust cell fate through modulation of energy production will add a novel method to interrogate and manipulate the regulatory network that defines the identity of human embryonic stem cells. The proposed studies will investigate how Akt interacts with other molecules in the power plant in human embryonic stem cells, how this new paradigm regulates energy production, and how such mechanism regulates stem cell fate and survival. Future therapeutic application of stem cells will rely heavily on delicate control of cell fate. We will test our hypothesis that human embryonic stem cell gene expression and cell fate can be altered by adjusting the power plant of stem cells. The results of this project will provide opportunities to identify new targets that can be used to manipulate embryonic stem cell fate in the future, and will advance our understanding of the relationship between regulation of energy production and stem cell fate.
A primary goal of CIRM is to translate basic stem cell research to clinical applications. The disability and loss of earning power and personal freedom resulting from a disease or disorder are devastating and create a financial burden for California in addition to the suffering caused to patients and their families. Therapies using human embryonic stem cells (hES cells) have the potential to change millions of lives. For the potential of hES cells to be realized, we have to decode basic mechanisms that direct stem cell development into specialized cells. Future application of stem cells will rely heavily on delicate control of cell fate. Potential ability to adjust cell fate through modulation of cellular signaling will add new method to manipulate the regulatory network that defines the identity of human embryonic stem cells. Potential benefits of this project to the Citizens of California include:
1. Development of new methods based on modulation of mitochondria function to direct the stem cell fate and stem cell viability, which may eventually be used to develop new strategies to design cell replacement therapies for human diseases.
2. Systemically screening and identifying new protein targets that may be used to develop new drugs and agents to promote stem cell function, thereby developing new treatment methods.
3. Transfer of new technologies and intellectual property to the public realm with resulting IP revenues coming into the state.
4. Creation of new biotechnology spin-off companies based on generated intellectual property.
5. Creating interdisciplinary research teams that will have a competitive edge for obtaining funding from out of state.
6. Creation of new jobs in the biotechnology sector.