44 - Investigating nsPEF Effects on Inner Nuclear Membrane Protein Function and Gene Expression
Description/Abstract/Artist Statement
Ultra short pulses of electricity (nanosecond duration; nsPEF) have negligible thermal effects on cells but impact inner structures of the cell. If the pulse duration is very short, the inside membranes of the cell become charged, affecting the cells in different ways, enabling novel therapeutic approaches. We investigate a relatively unexplored question in cell biology and biophysics, how does sub-lethal nsPEF exposure affect nuclear structure and gene expression and what are the consequences for the cell? The nuclear envelope is composed of inner (INM) and outer nuclear membranes. Proteins associated with the INM are multifunctional and regulate gene expression by 1); binding transcription factors in a manner that prevents their release into the nucleus to initiate gene expression, and 2); binding DNA to the INM that allows for DNA repair processes. Both binding mechanisms are dependent upon membrane/protein charges making them susceptible to nsPEF-induced changes to charge. We hypothesized that nsPEF will disrupt INM protein function, resulting in release of transcription factors and bound DNA from the inner nuclear membrane. We investigated nsPEF-induced changes in DNA and gene expression in normal primary cartilage-forming cells compared to cells from cartilage-forming tumors, aggressive malignant tumors resistant to chemo-and radiation therapies, desperately in need of new treatments. Preliminary data shows a small increased presence of transcription factor SMAD1/5 in the nucleus of all cell types following nsPEF and a significant increase in the formation of dicentric chromosomes suggesting nsPEF at sub-lethal doses impact the cell nucleus.
Faculty Advisor/Mentor
Michael Stacey
Faculty Advisor/Mentor Department
Department of Bioelectrics
College Affiliation
College of Sciences
Presentation Type
Poster
Disciplines
Cancer Biology | Cell Biology
44 - Investigating nsPEF Effects on Inner Nuclear Membrane Protein Function and Gene Expression
Ultra short pulses of electricity (nanosecond duration; nsPEF) have negligible thermal effects on cells but impact inner structures of the cell. If the pulse duration is very short, the inside membranes of the cell become charged, affecting the cells in different ways, enabling novel therapeutic approaches. We investigate a relatively unexplored question in cell biology and biophysics, how does sub-lethal nsPEF exposure affect nuclear structure and gene expression and what are the consequences for the cell? The nuclear envelope is composed of inner (INM) and outer nuclear membranes. Proteins associated with the INM are multifunctional and regulate gene expression by 1); binding transcription factors in a manner that prevents their release into the nucleus to initiate gene expression, and 2); binding DNA to the INM that allows for DNA repair processes. Both binding mechanisms are dependent upon membrane/protein charges making them susceptible to nsPEF-induced changes to charge. We hypothesized that nsPEF will disrupt INM protein function, resulting in release of transcription factors and bound DNA from the inner nuclear membrane. We investigated nsPEF-induced changes in DNA and gene expression in normal primary cartilage-forming cells compared to cells from cartilage-forming tumors, aggressive malignant tumors resistant to chemo-and radiation therapies, desperately in need of new treatments. Preliminary data shows a small increased presence of transcription factor SMAD1/5 in the nucleus of all cell types following nsPEF and a significant increase in the formation of dicentric chromosomes suggesting nsPEF at sub-lethal doses impact the cell nucleus.