Award Date: May 2011
Assistant Professor of Chemistry, Margot Paulick, has been awarded the Single Investigator Cottrell College Science Award through the Research Corporation for Science Advancement. The $35,000 grant for Dr. Paulick's project "Synthesis and evaluation of cell-permeable variants of trehalose to improve the viability of preserved mammalian cells" will support the development of a sustainable research program and enhance undergraduate involvement in research activities.
Live mammalian cells, such as red blood cells and human stem cells, are important for the success of many clinical and research endeavors. Unfortunately, current methods for the long-term storage of certain populations of these cells, including freezing or dehydrating, significantly decrease cell viability. Here we propose a novel “pro-drug” methodology for improving the survival of mammalian cells after freezing and dehydrating. Our strategy exploits the naturally occurring disaccharide trehalose (Tre), which enables cells to better survive extreme conditions, including freezing and almost complete drying. In order to function as a cellular protectant, Tre must be delivered to the intracellular environment; however, mammalian cell membranes are essentially impermeable to the hydrophobic sugar Tre. To overcome this obstacle, we will chemically synthesize cell-permeable Tre derivatives by protecting the hydrophilic hydroxyl groups of Tre with hydrophobic esters. After diffusion into the cell, these esters will be cleaved by nonspecific esterases, generating free Tre. We will then evaluate the ability of these sugars to prevent mammalian cell damage during cryopreservation and desiccation. Ultimately, our proposed research can be used to improve the viability of stored blood and human stem cells, thus increasing the success of blood transfusions and stem cell therapy.