Proteins have many different roles within our bodies. They are coded for by our genes and form the basis of living tissues. They also play a central role in biological processes. For example, proteins catalyse reactions in our bodies, transport molecules such as oxygen, keep us healthy as part of the immune system and transmit messages from cell to cell.
Dr Julia Horsfield leads the Chromosome Structure and Development Group at the University of Otago. Her lab investigates how cohesin proteins, which regulate chromosome structure during cell division, play a role in regulating gene expression. This research is significant for both human developmental disease and cancer.
Cohesin proteins and cell division
Cohesin proteins play a critical role in cell division during mitosis. After the chromosomes are replicated, they line up along the middle of the cell and then are pulled to the 2 opposite ends of the cell, allowing the cell to divide down the middle. Cohesin proteins hold the chromosomes together at the start of the process so that they are lined up and pulled apart correctly. This role and process is relatively well understood.
Over the past 6 or 7 years, a number of scientists, including Julia, independently discovered that cohesin proteins have other roles when they have finished holding the chromosomes together. These other roles involve regulating the expression of genes that need to be turned on or off at particular times during development.
Alternative roles of cohesin proteins
Julia made her discovery while investigating the expression of runx genes in zebrafish embryos. Runx genes control the early development of blood cells, and Julia discovered that cohesin proteins turned these genes on.
At the time, this result was a confusing one. Why were cohesin proteins turning on runx genes? Julia, as well as other scientists around the world, started to realise that cohesin proteins were playing additional roles in development. In particular, cohesin proteins were involved in making sure that genes are switched on or off at the correct times during development.
Zebrafish as a model organism
Julia’s lab uses zebrafish as a model to understand the early development of human disease. Their embryos develop externally in transparent eggshells, making it possible to watch the animal develop through a microscope over a couple of days.
This enables scientists to pinpoint where changes in development lead to developmental disorders like Cornelia de Lange syndrome, which affects arm development in humans. Although fish don’t have arms, the same genes that control development of pectoral fins in the fish are studied. Julia and her colleagues focus on the impact of a reduction in cohesin proteins on gene expression in zebrafish and use these results to better understand the human disease.
Genetic research and future medical treatments
Julia acknowledges that effective preventive therapy for many genetic disorders, including Cornelia de Lange syndrome, is a long way away. However, the more that we understand about the developmental processes that cause such syndromes, the better we are able to support sufferers when they are born. In the longer term, this research also takes scientists a step closer to preventing or treating many human syndromes.
Learn more about the use of zebrafish in genetic research. In this RNZ interivew Julia Horsfield and Jenny Rhodes explain how zebrafish are helping in genetic research into diseases like human cancers
Nature of science
Key scientific discoveries are often the result of looking more closely at unexpected or surprising results. Scientists working independently may find that they are asking the same questions or making the same discoveries as each other.