Mixing mercury with a biological system may not be the most obvious experiment but scientists in Germany and Spain have done just that. They have used a derivative of the toxic element to detect low abundance proteins, a common challenge for scientists trying to identify trace proteins linked to disease.

Disease-associated proteins are typically found through proteomic studies - studies that look at all the proteins produced by an organism or system. However, proteins of interest are often not the most common and it can be difficult to detect and quantify them in samples. Now, a team led by Jörg Bettmer, of the German Cancer Research Center in Heidelberg, has developed a way of labelling proteins that enables them to be studied at much lower concentrations.

Tagging the protein ovalbumin with a mercury derivative improves its detection by ICP-MS

Bettmer explains that the group had already used elemental tags such as sulfur and phosphorus to quantify proteins using the mass spectrometry technique ICP-MS (inductively coupled plasma-mass spectrometry). But such tags have relatively high detection limits, reducing the technique's applicability. The way to lower the detection limit and make low abundance proteins 'visible' using ICP-MS is to label them with tags containing heavier and less common elements, such as mercury, says Bettmer.

The group used the mercury-containing compound, p-hydroxymercuribenzoic acid (pHMB) to tag ovalbumin, a protein found in egg white, at different concentrations in solution. By subjecting the solutions to ICP-MS they found that the technique's detection limit was substantially improved compared to sulfur tagging. Mercury is toxic because it bonds so well to the cysteine side chains that are prevalent in enzymes and proteins and the pHMB tag uses this feature of mercury's chemistry to its advantage.

'Labelling concepts in combination with ICP-MS is a relatively new and exciting field of research,' Bettmer says. For quantitative protein studies, the outcome of uniting the techniques will be 'enormous' he adds.

Laura Howes