Non-genetic heterogeneity originating at cell division
소속 :
연사 : Dr. Dann Huh (Harvard University)
일시 : 2012-11-20 15:00 ~
장소 : 502동 227호
일 시 : 2012년 11월 20일, 3:00 PM
장 소 : 502동 227호
-Abstract-
Many RNAs, proteins, and organelles are present in such low numbers per cell that random segregation of individual copies causes large ‘partitioning errors’ at cell division. Even symmetrically dividing cells can then by chance produce daughters with very different composition. In my theoretical work, I mathematically demonstrate how partitioning errors arise for different types of segregation mechanisms and how they contribute to the non-genetic heterogeneity in growing and dividing cells. The results show that such errors can be greatly increased by upstream randomness but remarkably hard to avoid through controlled partitioning, or to correct once they arise. By combining our theoretical results with the broad range of previous experimental findings, and separating between actual creation versus mere transmission of noise, I conclude that much of the cell-to-cell heterogeneity that has been attributed to for example the randomness of gene expression may in fact originate in segregation. In my experimental work, I use Schizosaccharomyces pombe as a model organism to measure the partitioning errors of 35 different proteins from different cellular compartments. Proteins in mitochondria and vacuoles exhibit about 2~3 fold higher partitioning error than the partitioning error of cytoplasmic volume (Qv). In contrast, most of the other proteins show comparable amount of partitioning errors to Qv, irrespectively of their localization. However, unevenness of ER and nucleus at cell division has additional source of randomness than the difference in cytoplasmic volume. I also found that partitioning errors contribute 30~60% of the total heterogeneity of the newborn population, depending on proteins and their localization. Therefore, partitioning errors, which has often been ignored, can be an important source of cell to cell variability.
장 소 : 502동 227호
-Abstract-
Many RNAs, proteins, and organelles are present in such low numbers per cell that random segregation of individual copies causes large ‘partitioning errors’ at cell division. Even symmetrically dividing cells can then by chance produce daughters with very different composition. In my theoretical work, I mathematically demonstrate how partitioning errors arise for different types of segregation mechanisms and how they contribute to the non-genetic heterogeneity in growing and dividing cells. The results show that such errors can be greatly increased by upstream randomness but remarkably hard to avoid through controlled partitioning, or to correct once they arise. By combining our theoretical results with the broad range of previous experimental findings, and separating between actual creation versus mere transmission of noise, I conclude that much of the cell-to-cell heterogeneity that has been attributed to for example the randomness of gene expression may in fact originate in segregation. In my experimental work, I use Schizosaccharomyces pombe as a model organism to measure the partitioning errors of 35 different proteins from different cellular compartments. Proteins in mitochondria and vacuoles exhibit about 2~3 fold higher partitioning error than the partitioning error of cytoplasmic volume (Qv). In contrast, most of the other proteins show comparable amount of partitioning errors to Qv, irrespectively of their localization. However, unevenness of ER and nucleus at cell division has additional source of randomness than the difference in cytoplasmic volume. I also found that partitioning errors contribute 30~60% of the total heterogeneity of the newborn population, depending on proteins and their localization. Therefore, partitioning errors, which has often been ignored, can be an important source of cell to cell variability.
