Investigating mRNA methyl cap regulation, function and therapeutic potential

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Victoria Cowling's lab at the University of Dundee investigate how proteins are made in human cells, with the aim of uncovering new approaches to stop the growth of cancer cells and parasites. The human body is made up of trillions of cells with many different functions, e.g. skin, muscle, gut cells. Our health is dependent on these cells responding rapidly to the "instructions" they receive from the body on how to function and whether to grow and multiply, rest or die. In this way, trillions of cells can co-ordinate their activities to form the human body. In cancer, our cells become less responsive to these instructions, and grow and divide in an uncontrolled manner. As a result masses of cells accumulate, often forming cancerous tumours. Cancer researchers investigate why cancer cells become unresponsive to instructions from the body, with the aim of developing new therapies to stop cancer cells growing. Cells are built from proteins and therefore for cells to grow and divide, new proteins need to be made. DNA found in our genes holds the "recipe" for making proteins, but it uses a messenger called RNA to provide precise instructions for proteins. Victoria Cowling's lab is investigating how the RNA messenger is made and handled in the cell, and how it is read to make proteins. Specifically, the Cowling group investigates a structure called the "methyl cap" which flags certain RNAs to be used to make proteins. They discovered that the methyl cap can be influenced by cancer-causing oncogenes and that it is needed for a certain oncogenes to function. Encouraged by these initial results, the Cowling group has initiated a programme of research investigating how the methyl cap is synthesized and regulated in the cell, and how this process goes wrong in cancer cells. They are also collaborating with the Dundee Drug discovery unit to use cutting-edge technology to look for new chemical compounds that stop the methyl cap from forming. Such compounds may form the starting point for developing new anti-cancer therapies. Since human parasites are also dependent on the methyl cap to make protein, Dr Cowling is collaborating with Prof Mike Ferguson at the University of Dundee, to investigate targeting the methyl cap in the parasite, T. brucei, which causes African Sleeping Sickness, a debilitating disease for which treatment remains limited.