Beam-time for biology

There's no question that playing with mercury or handling radioactive cadmium with your bare hands is a risky business. But understanding how these and other toxic metals interact with biomolecules within the body is a challenging feat; one for which the ISOLDE IS488 collaboration hopes to provide valuable insight.

 

Unlike most of the facilities at CERN's accelerator complex, ISOLDE is not targeted mainly at particle physics. Rather, it produces radioactive nuclei during proton bombardment to study, among other things, physical and biological chemistry.

At ISOLDE, the 1.4 GeV proton beam of the PS Booster (an early stage in CERN's accelerator complex) produces nuclear reactions in a thick target, creating a large variety of radioactive nuclei, which are mass-separated for use in experiments.
In the case of the IS488 collaboration, the ion beam is directed into ice. "We implant radioactive metal ions into ice", explains Monika Stachura, a physicist from the University of Copenhagen, "We transport the ice into our chemistry lab here at CERN, let it melt and then add proteins and chemical solutions to it, such as buffers to control pH. This protein solution is then placed in the gamma-ray Perturbed Angular Correlation (PAC) instrument, which allows us to observe how, for example, the toxic metals alter the protein structure, probably preventing the normal physiological functions of these biomolecules".
The PAC instrument is composed of six detectors that record the emission of two coincident gamma rays from the radioactive isotopes. This technique allows the study of molecular structure in close proximity to the isotope.

As Monika explains, certain radioactive ions have the ability to substitute for the metals that are found in biological proteins. "The radioactive ions that we use in our experiment have a high affinity to the binding sites in proteins that are occupied by natural metal ions. One third of all the proteins found in our bodies contain metal ions that are vital for their structure, proper functioning and biological interactions. Thus, it is possible to study the actual function of the biomolecules, provided that they are still physiologically active.”

So far, the IS488 collaboration at CERN has studied the effects of mercury, lead and cadmium isotopes. Its research also provides experimental data to help understand the structure and function of proteins, as well as DNA and RNA. In particular, the ETHZ has sent samples of metallothionein to CERN so that its role in the biological self-protection of human bodies and plants can be studied. "Metallothionein is a naturally occurring protein that, among other functions, searches for toxic metal ions within a living organism, finds them and binds them. Using our technique, we can even study whole plants in vivo", explains Monika.

Although the collaboration is presently limited to studying a narrow group of isotopes, it is able to make extrapolations about the most important metal ions found in the body, such as copper, zinc and magnesium, which cannot be studied directly using most spectroscopic techniques. However, a new instrument for beta-NMR spectroscopy – which involves the use of beta emitters – has been designed by Alexander Gottberg, an IS488 collaboration member from the University of Copenhagen.This may allow these ions to become visible so that the extrapolations that have been made can be verified. The first experiments ever conducted on bio matter with this technique are planned for next year.

by Jordan Juras