By Alison Ballance Alison.Ballance@radionz.co.nz
Protein crystals that have been prepared from purified protein (left), and researchers Catherine Day and Adam Middleton in front of an electron density map. Photo: Josh Wright (left) RNZ / Alison Ballance (right)
Human beings are made up of billions of cells, and those cells need to communicate amongst themselves and also within themselves.
“We’re a big collection of millions and billions of cells, and they have to be good citizens really, and talk to their neighbours,” says Catherine Day. “And they all need to communicate, and effectively they need to know when to divide, and when to respond in a given way, for example when we’ve just eaten. They need to respond to stresses like viruses, and then sometimes they need to die. And we’re particularly interested in the dying cells. So dying is good. Every day about 60 billion cells in you and I die.”
Protein biochemist Catherine Day from the Biochemistry Department at the University of Otago studies how molecules interact and how they regulate signalling pathways. She says that a lot of diseases, such as cancer, are a case of cells not dying when they should, and that her research focuses on understanding the processes that cause cells to die.
A 3D electron density map of a protein produced after the protein crystal has been x-rayed from 360 different angles (above), and protein structures represented in a ribbon diagram (below) which shows how they link or bind to each other. Photo: Martina Foglizzo (left) Adam Middleton (right)
Much of the communication by cells is done by proteins, which Catherine describes as the ‘machines’ of the cell. “They’re the enzymes and a lot of the signalling molecules within a cell.”
“At the heart of what we do is working out the three-dimensional molecular structure of proteins,” says Catherine. “And then that tells us a lot about the functions, how they interact and how they are folded up. Their function is strongly related to their structure.”
Catherine and her team, including post-doctoral researcher Adam Middleton, spend much of their time using x-ray crystallography to work out the structure of different proteins. They are particularly interested in a common regulatory protein called ubiquitin that is found in almost all living tissue.
They begin by concentrating protein and creating crystals, which are then examined under x-ray. They are x-rayed from 360 different angles which creates a 3D electron density map that allows the researchers to see how different proteins bind to one another. The end result of their work is a simple ribbon diagram which illustrates the structure and linkages of different proteins.
This work helps in understanding what happens with diseases such as cancer at a cellular level, and provides a base from which to develop anti-cancer drugs.
“If we want to disrupt a particular interaction between proteins, then by understanding how they bind then you can think about ways to design molecules to block that interaction,” says Catherine.
Catherine Day is talking on 'The life and death of a cell' in Nelson on Tuesday 30 September. her talk is part of the Royal Society of New Zealand's Ten By Ten lecture series being held to celebrate 20 years of Marsden-funded research.
