Dissecting the regulatory roles of 14-3-3zeta on the adipogenic transcriptional program

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The growth of a fat cell, or adipocyte, is a complex process that involves a complicated network of proteins. These proteins need to be in the right place and time, but it is not well known what factors within the fat cell coordinate the actions of these proteins. Molecular scaffolds are possible candidates because of their abilities to help proteins connect with one another and to keep them in different areas of a cell. Previously, I have found that one molecular scaffold called 14-3-3 was required for fat cell development. Mice that did not have 14-3-3, were very lean and had less fat. On the other hand, mice that had increased amounts of 14-3-3 in every cell became fatter when fed a diet rich in fat. Despite these roles in controlling the amount of fat, the specific mechanisms of how 14-3-3 controls fat cell growth requires further investigation. 14-3-3 and other members of this protein family are unique because they are able to connect with a diverse group of proteins, and this suggests that they may control the growth of a fat cell through multiple pathways and mechanisms. Therefore, the goals of this proposal are to explore and define these pathways in order to better understand how fat cells are formed. To better understand the role of 14-3-3 in the growth of a fat cell, a new cell model will be made with CRISPR-Cas9 technology to insert a modified version of 14-3-3 in the cell. This will allow for the simple and clean extraction of 14-3-3 in order to see what types of genes it may control, as well as the identifies of proteins that it may touch, connect, and influence. I anticipate that these proposed studies will identify new players that are involved in the growth of fat cells. Aside from other researchers who study fat cell development, this work has the potential to be applied to other cell types across different fields of study. Results from the proposed studies will increase our understanding of how different types of cell develop and will reveal how the actions of proteins are coordinated in a cell. Furthermore, knowledge gained from these studies may be applied to the development of new therapies that are influenced by increases in body fat, such as obesity, heart disease, and diabetes.