Which genes dictate the life and death of cells? A team led by Prof Jochen Prehn hopes to find out, writes Dick Ahlstrom
Individual cells know when it is time to go and they initiate their own spontaneous death. This process can go dangerously wrong in a number of diseases, however, and a Dublin research group hopes to discover ways to control this.
The Royal College of Surgeons in Ireland (RCSI) runs a very active research group studying the cell suicide process, known as apoptosis. It involves a team of 20 to 25, explains the head of physiology and medical physics at RCSI, Prof Jochen Prehn.
"The goal is to identify the link between cell stress signalling and cell shutdown," he says. "We find there is a fine balance between cell survival or death when under stress."
Death is a part of life when it comes to the cells in our bodies. Unwanted or ageing cells undergo apoptosis as a highly controlled and safe way to dispose of themselves.
Very complex signalling is involved to initiate this process and Prehn's group studies both the signals and the expression of proteins that begin the apoptotic cascade of events leading to cell death.
Things go wrong in diseases such as cancer, however, where cells refuse to die on cue. Others include Parkinson's disease and motor neuron disease, where cells go into apoptosis too soon and central nervous system cells are lost too quickly.
Prehn came to Ireland in July 2003 to take up a Science Foundation Ireland research professorship at RCSI. He was already a noted researcher specialising in death signalling in neurons and he has continued this work here.
Teams within his group are working on epilepsy, on damage caused by stroke and on motor neuron disease. "We are trying to identify the genes that dictate cell survival or death," he explains.
The research is conducted both in vitro and in vivo. Cell cultures derived from mouse hippocampus cells are used to study the up and down regulation of proteins inside the cell after stressing the cells. In this way they can watch what the deciding factors are between cell survival and death.
They also use a mouse model for motor neuron disease that closely matches progress of the disease in humans, but with a disease process lasting 15 to 20 weeks rather than years. "We can see how the genes behave in vivo. There is a great need for in vivo models for these diseases," Prehn says.
Microarrays and related technologies are used to sample the proteins being expressed after a cell has been stressed, for example, through reduced blood flow. "If we know a certain protein is important, for example in ischemia, we know there is misfolding of protein structure under stress," says Prehn.
They can watch for proteins that helped to tip the balance between cell survival or death, and if found, this discovery opens up opportunities for new drug therapies, he explains. If they can identify the protein pathways for proteins that improve survival, then perhaps drugs can be found that enhance this effect, he says. "We try to boost the cell survival response and by doing this you can make cells more resistant [ to apoptosis] even after the onset of disease. We want to identify ways that signalling can be boosted."
It also works the other way, particularly in cancer. "In this case we want to find treatments that sensitise cells to apoptosis." Drugs in this case would encourage cancer cells to relearn the rules and become susceptible to apoptosis again.