So Hamza did the non-intuitive thing. He chose a test subject that doesnt make heme, but needs it to survive, that doesnt even have blood, but shares a number of genes with humans the C. elegans roundworm, a simple nematode.
We tried to understand how blood is formed in an animal that doesnt have blood, that doesnt turn red, but has globin, Hamza said.
C. elegans gets heme by eating bacteria in the soil where it lives. C. elegans consumes heme and transports it into the intestine. So now you have a master valve to control how much heme the animal sees and digests via its food, Hamza explains.
C. elegans has several other benefits for studying heme transport. Hamzas team could control the amount of heme the worms were eating. With only one valve controlling the heme transport, the scientists knew exactly where heme was entering the worms intestine, where, as in humans, it is absorbed.
And C. elegans is transparent, so that under the microscope researchers could see the movement of the heme ingested by the worm.
Genes and Iron Deficiency
The study revealed several findings that could lead to new treatment for iron deficiency. One was the discovery that genes are involved in heme transport. Hamzas group found that HRG-1 genes, which are common to humans and C. elegans, were important regulators of heme transport in the worm.
To test their findings in an animal that makes blood, Hamzas team removed the HRG-1 gene in zebrafish. The fish developed bone and brain defects, much like birth defects. The gene removal also resulted in a severe form of anemia usually caused by iron deficiencies.
When they substituted the zebrafish gene with the worm HRG-1 gene, the mutant fish returned to normal, indicating that the fish and worm genes are interchangeable, irrespective of the animals ability to make blood.
They also found that too little or too much heme can kill C. elegans, a result that could help resear
|Contact: Ellen Ternes|
University of Maryland