A thermodynamic pathway to intracellular delivery. Cells transmit information through molecules. By delivering foreign molecules into cells, such as DNA and proteins, it is possible to engineer and reprogram cells just like a computer. This proposal aims to develop a novel microfluidic device for intracellular delivery. The device will work by exposing cells to rapid thermal shock to generate transient disruptions in cell membranes and thereby enable influx of foreign molecules into cells. To un ....A thermodynamic pathway to intracellular delivery. Cells transmit information through molecules. By delivering foreign molecules into cells, such as DNA and proteins, it is possible to engineer and reprogram cells just like a computer. This proposal aims to develop a novel microfluidic device for intracellular delivery. The device will work by exposing cells to rapid thermal shock to generate transient disruptions in cell membranes and thereby enable influx of foreign molecules into cells. To understand how the method can be optimized, the thermodynamic pathway of membrane disruption will be investigated at a single cell level. The methods and insights arising from this project could eventually lead to novel, patentable and lower-cost health technologies.Read moreRead less
The “New” Biochemistry of Polyamines: When Metabolic Pathways Collide. Basic biochemistry and the metabolic regulation of proliferation remain as the fundamental building blocks of knowledge in cell biology that have enabled breakthrough advances in biology and medicine. Polyamines are unique and ubiquitous low-Mr amines that play vital roles in many biological processes, including proliferation, DNA/RNA synthesis, etc. This proposal will mechanistically dissect the "new" biochemistry of polyami ....The “New” Biochemistry of Polyamines: When Metabolic Pathways Collide. Basic biochemistry and the metabolic regulation of proliferation remain as the fundamental building blocks of knowledge in cell biology that have enabled breakthrough advances in biology and medicine. Polyamines are unique and ubiquitous low-Mr amines that play vital roles in many biological processes, including proliferation, DNA/RNA synthesis, etc. This proposal will mechanistically dissect the "new" biochemistry of polyamines, as we have discovered that polyamines are regulated by iron at 2-major levels, involving >10-key polyamine pathway proteins. This proposal represents first-in-field studies specifically designed to dissect mechanisms involved in this relationship. Our Central Hypothesis is that iron regulates polyamine metabolism.Read moreRead less