Frogs and humans have more in common than you'd think, according to a UCD research team. Danielle Barron reports.
You may not be familiar with a creature called Xenopus, but you have quite a lot in common with it. Researchers in UCD's Conway Institute have been exploring the links between humans and this particular species, better known as the African clawed frog. Along the way, they have uncovered secrets about our cells' resistance to cancer.
Xenopus laevis embryos develop very quickly, making it a particularly attractive system for studying the machinery of the cell, explains Dr Carmel Hensey of the school of biomedical and molecular science. Many of its genes can also be found in humans, she adds.
"This frog has been used as an experimental model for well over a century and most of the genes and machinery that we study in Xenopus are also functional in humans."
Her group has worked with Xenopus since 2000 in research funded by the Wellcome Trust and the Irish Research Council for Science, Engineering and Technology (IRCSET). "We keep a large colony of frogs here, and so easily generate a lot of frogspawn," she explains.
Just one millimetre in size, the Xenopus embryo is surprisingly robust. It was during her postdoctoral studies that Hensey first became aware that the early embryo is insensitive to high doses of radiation, or is radio-resistant. As it grows it later becomes radio-sensitive.
Some cancerous tumours in humans are also radio-resistant and thus don't respond to radiation treatment. Hensey and her group are seeking to understand the molecular basis of this shift in sensitivity.
Radiation treatment attempts to activate the cellular machinery that leads to cell suicide, explains Hensey. There are specific genes important for this cell suicide, and one that Hensey and her research group have been looking at is p53, the tumour-suppressor gene.
This gene literally suppresses tumour growth, killing off any cells that threaten to turn cancerous. It is thought to malfunction in around 50 per cent of all cancers and various studies have shown that p53 in Xenopus is largely equivalent to the p53 gene in humans.
There is a very small level of p53 protein present in normal human cells and it is almost impossible to detect, says Hensey. But when a cell is subjected to a stress such as radiation or UV light, the amount of p53 protein in the cell rises rapidly.
"When you get a sunburn, and the skin starts peeling, that's activation of p53," explains Hensey.
This is not the case with Xenopus embryos however. "In normal cells, p53 can be quite difficult to study as you have to stress the cell to see the protein, whereas in these embryos we have quite high levels of p53," says Hensey, adding that this makes it easier to study the modifications responsible for stabilising the protein and causing the amounts found in cells to rise.
"But there are lots of other modifications and there is a lot of controversy out there as to exactly what each modification does," she states.
Staining the embryos using a technique known as whole mount immunohistochemistry allows Hensey and her team to view the exact location of p53 within each cell. This spatial information, says Hensey, will help us understand more about the nature of p53's efforts to protect us from cancer.
Claire Moran, a PhD candidate in Hensey's lab, has been working on characterising the various modifications, and linking these results with the location of p53 within the cell and also the types of p53 present.
"Seeing the exact location of the protein, for example whether it's in the cytoplasm or the nucleus, gives us ideas as to what it's actually doing," explains Moran. Her work has also shown that there seems to be a whole range of different types of p53, information that Hensey sees as valuable when looking at targets for future cancer treatments.
"You really need to know a lot about the milieu the protein is in, for example what its partners are, and what other proteins are regulating it, so that you have lots of choices in terms of what way to target the protein when designing a new therapy."