Prof Kate Loveland
To discover how cells grow and differentiate in a highly regulated manner, we have been investigating a group of proteins that carry cargo proteins into the cell nucleus in order to turn genes on and off. These transporters are named "importins".
The present study capitalizes on the high end microscopy capabilities of the Monash Micro Imaging Platform to show how levels of individual importins determine the formation of bodies within the nucleus involved in controlling gene activity, termed paraspeckles. Dr Andy Major (formerly a MIMR PhD student) developed a mathematical approach to create a 'bioinformatic pipeline' that can compare hundreds of cells grown in culture, to and examine over 100,000 of these nuclear bodies in a single experiment.
The results show that the levels and relative ratios of specific importin proteins in a cell dictate the size and number of the nuclear paraspeckles.
Centre for Reproductive Health
Testis Development and Germ Cell Biology
Journal and article title
Development of a pipeline for automated, high-throughput analysis of paraspeckle proteins reveals specific roles for importin α proteins
We discovered that the capacity to examine such large number of cells allows us to analyze samples that are not manipulated in any way, and from this we can record how levels of importin levels vary between cells and how this affects the function of each individual cell. We can apply this to examine cells from patients with tumours in which importins are abnormally elevated, so we can learn more about how this aspect of cancer biology affects cell growth and survival.
This research has provided a new way to study the normal processes of development that are required to make different kinds of cells. As part of our efforts to understand what controls sperm formation, our ongoing work has revealed that one particular importin is essential for for fertility, because mice lacking this gene don't make sperm or egg cells. The latest study provides a new approach that can be applied to real cells in animals to learn how each step of development occurs, including through regulated transport of key proteins into the nucleus. We will be able to apply this to patient samples where there are normal and diseased cells side-by-side, to learn more about how cancer cells may outgrow healthy cells.