A news research centre looking at how DNA carries out its own repoairs will bne announced today, writes Dick Ahlstrom.
ADVANCED CANCER research at NUI Galway receives a boost this morning with a €3.5 million research award from Science Foundation Ireland. The money will support a team of 10 who will focus on developing new ways to study the biology of cancer over the next five years.
The principal investigator award is for work headed by Prof Noel Lowndes, Galway's chair of biochemistry and head of a research group which he founded, the Centre for Chromosome Biology.
Formerly the Genome Stability Cluster, it has received support worth €15 million since opening in 2002.
The centre now has 40 full-time researchers but has a unique structure in that it involves the efforts of 10 independent principal investigator-led laboratories. While each involves its own team of researchers, all seek to increase our understanding of how the cell maintains the structure of its DNA and how it repairs itself, Prof Lowndes explains.
It also has an international dimension given there are collaborating labs in the US and Japan. Funding for the centre comes from SFI but also the Health Research Board, the Higher Education Authority, the EU, Cancer Research Ireland, the Wellcome Trust and the US National Institutes of Health.
"We are trying to understand how the cell maintains genome structure, how the package of DNA and its protective proteins is kept in order," he says.
DNA is a hugely complex, large-scale molecule. It must be copied exactly each time the cell divides but the cell must also ensure it maintains its integrity in the face of damage caused by "genotoxins", tobacco smoke, chemicals, ionising radiation, ultraviolet radiation and free oxygen.
It is all about "the regulation of chromosome structure", something that is particularly important in the development of cancer, Prof Lowndes says.
"Cancer is fundamentally a problem of genome structure, genes are inappropriately turned on and off. It is critically important."
The Centre for Chromosome Biology looks in detail at how the cell deals with damage to its DNA. "We are studying the cell's response to the genotoxin. It is relevant because these agents in the natural world actually cause cancers," says Prof Lowndes.
"The cell can sense a double strand [DNA] break and immediately sets in motion a repair mechanism. It is really important that the mechanism gets there as quickly as possible to initiate a repair."
The process is extremely elaborate and hundreds of genes are recruited into the process to reinstate the integrity of the DNA. This process is literally a life or death activity for the cell given there are biochemical "checkpoints" that determine whether a cell is dividing properly, Prof Lowndes explains.
IF THE CHECKPOINT senses there is a problem it releases proteins to halt cell division until it can analyse whether a repair is possible. If not it will trigger apoptosis, automatic cell death, and the cell is eliminated.
This process goes wrong in cancer and the cell evades apoptosis.
Prof Lowndes wants to know exactly what happens, step by step, in this process.
"In my lab we are interested in the really early biochemistry, right after the damage is caused."
His new team will create fresh ways to study these processes. Current techniques involve using a gamma ray radiation source to cause DNA breaks in cultured cell lines using human, chicken and yeast cells.
It is valuable, however, to be able to put in and take away specific genes from the cell lines, so his team is going to make use of a new cell type derived from chicken tissue which has this attribute, known as DT40 cells.
"We are going to develop a new model system that is closer to human cells," he says.