Making things smaller to make them bigger

One of our main research directions is the development and optimisation of bioanalytical tools. In terms of optimisation, among others we seek to make the bioassays more versatile, meaning to include several different effect meaurements and integrate results; to allow for a higher throughput of samples, thus reducing required work force and other resources; and to miniaturise the bioassays where possible, especially with regard to saving sample.

The latter one was the focus of a study we conducted on an assay that detects androgen receptor binding, thus indicating potential for hormon-like activity and disturbance of the endocrine system. Samples containing such substances are often available in only very small amounts, for instance as extracts from water samples. And especially in terms of drinking water the presence of androgen-like chemicals is a great concern.

We succeeded in reducing the medium volume to dilute the sample to one third of what is recommended by the standard protocol, thus also significantly reducing the required amount of sample. Results obtained for standard substances were compared to data obtained using the conventional procedures and found to be similar. This proved that the optimised method can be applied as an alternative to the standard protocol, if limitations by small sample amounts would otherwise prohibit scientifically meaningful investigations, and thus compromise proper risk assessment.

Take a closer look at the "Downscaling procedures reduce chemical use in androgen receptor reporter gene assay". (fulltext only with a subscription to the journal, sorry...)

This is a boring headline about zebrafish embryos exposed to heavy metals

Today I report on a study that was published already a while ago, but tells a nice story about the challenge and necessity to design meaningful experiments. Also, this one deals with heavy metals, which is not common in our research; we mainly focus on organic contaminants.

In this particular study we investgated whether heavy metals spiked into sediments are bioavailable to unhatched zebrafish embryos, and whether it makes a difference if the sediment was a natural one - just taken from, e.g., a riverbed out there - or a formulated, meaning components that typically make up a sediment mixed together. Besides the single heavy metals we also spiked mixtures.

We investigated mortality, several heavy metal-specific proteins and the regulation of a couple of genes that are known to react to heavy metal exposure. What we found was actually not very surprising: the heavy metals in the formulated sediment were better bioavailable than those in the natural one. An artificial mixture of sediment components can never resemble a real "grown" sediment. The matrix in the natural sediment is just much more complex and provides a multitude of possibilities for heavy metals to be trapped, bound, blocked, and thus not able to enter the test organism. Nevertheless, this had to be proven first. Science does not rely on hypotheses. We  have to challenge them to be sure.

However, formulated sediments are widely used in research. And our study shows that using such matrices could largely overestimate bioavailability and thus risk of heavy metal contaminations in sediments. Furthermore, the study revealed that the accumulation of the individual heavy metals from a mixture is relatively lower compared to that in the single metal exposure experiments. Since not all metals show the same toxicity for the embryos this has to be taken into account when doing risk assessment of heavy metal burden.

Last not least we identified some promising biomarkers for low-dose detection of heavy metal exposure. Read the full story on "Bioaccumulation and molecular effects of sediment-bound metals in zebrafish embryos". (fulltext only with a subscription to the journal, sorry...)