Baker's yeast key to human protein research

It took simple baker’s yeast and a hunch about the mysterious behaviour of a protein. Now, a Massey University scientist’s research has paved the way to understanding how the protein Gcn2, which resides in all living organisms, affects memory, immunity and diseases such as cancer, dementia and obesity.

Dr Evelyn Sattlegger, and her research group at the Institute of Natural Sciences at the Albany campus, along with collaborators in the United States and Brazil, have discovered that the protein eEF1A (a protein synthesis factor) keeps Gcn2 in check – a finding that provides a better understanding of finely tuned cell interactions that ultimately underpin our health.

The study has just been published in the international Journal of Biological Chemistry, and was selected as paper of the week for October 21, ranking it in the top one per cent in terms of overall significance.

Dr Sattlegger says she and her colleagues have provided insights into a new mechanism of Gcn2 regulation, adding to the theoretical framework that maps the mechanisms of how Gcn2 functions properly. Understanding this function will provide a basis for further applied medical research, she says.

The study has wide ranging implications for understanding human health, and prevention of disease, says Dr Sattlegger, who has long been fascinated by these proteins that have been poorly understood by scientists to date.

“We’ve been able to open a door into the complexities of how the two proteins work together to allow cells to know when they are short of amino acids – the building blocks of proteins which are needed for almost all biological functions – and how to cope with the problem.”

“Knowing how cells detect and regulate amino acid levels will be very useful, particularly because Gcn2 is implicated in a number of diseases, and in diverse processes, like long-term memory function, viral defence and in silencing the immune system,” she says.

Researchers carried out a variety of genetic and biochemical analyses using baker’s yeast. “We used basic yeast because it closely mimics the same process in human cells,” says Dr Sattlegger.

The experiment led to the “novel” discovery that Gnc2 is involved in a sort of reciprocal regulatory process with protein synthesis. “Precise knowledge of Gcn2 regulation will allow us to develop measures against Gcn2 associated diseases,” says Dr Sattlegger. “In particular Gcn2 has been proposed to be a promising target for anti-cancer drugs.”