February 2011 - Injecting zebrafish at high speed
Zebrafish are extremely suitable for studying tuberculosis. Leiden researchers have succeeded in automating critical experimental steps using zebrafish embryos; their findings appear on the February 16 issue of the scientific journal PLoS ONE. Their work will enable a faster, better understanding of tuberculosis progression, and how it may be halted.
One-third of the world population is infected with Mycobacterium tuberculosis, the tuberculosis-causing bacterium. Although infection does not always result in full-blown tuberculosis, 9.4 million people contracted the disease in 2008 alone, according to the World Health Organisation. A number of antibiotics are available to combat the disease, but tuberculosis bacteria are becoming increasingly resistant to existing drugs.
Close-up of a Mycobacterium tuberculosis colony, responsible for tuberculosis. (Photograph Wikimedia Commons)
- Ideal tuberculosis model
Zebrafish are cheap, they reproduce very quickly and their embryos are transparent. Infection with fluorescently-labelled tuberculosis bacteria can be followed over time, allowing the spreading of the disease to be studied. Commonly, only Mycobacterium marinum (a close relative to Mycobacterium tuberculosis) is used as a tuberculosis-causing agent in zebrafish. This infection leads to symptoms similar to those found in humans, and make the zebrafish a powerful model organism to study this disease.
The researchers injected 1-day-old zebrafish embryos. Here they are 4 days old. (Photograph Wikimedia Commons)
Leiden researchers, under supervision of molecular biologist Herman Spaink, have achieved a breakthrough in the study of tuberculosis using the zebrafish embryo. They have developed an automatic injection system that allows the fast and reliable infection of 1000 embryos in 30 minutes, removing the bottleneck caused by the time- and labour-intensive manual injection of embryos.
- Testing new drugs
The high level of throughput of the system developed in the Leiden Cell Observatory enables the study of large panels of candidate drugs against tuberculosis, which will hopefully lead to effective new therapies to combat this disease. Interestingly, this research shows how the automatic injector can infect zebrafish embryos with M. tuberculosis, allowing the direct study of the human pathogen. This technology may therefore play an important role in the global efforts to eradicate drug-resistant tuberculosis strains.