08 April 2010

Diseases are growing by leaps and bounds

Human diseases began to be studied on yeast and plants
Alexey Timoshenko, GZT.RUIt is possible to study human diseases not only on animals, but also on plants and even yeast.

Biologists presented a review devoted to unusual methods of disease research.

The journal Proceedings of the National Academy of Sciences has published a review article (Kriston L. McGary et al., Systematic discovery of nonobvious human disease models through orthologous phenotypes), prepared by biologists from the University of Texas (USA). The researchers consider the so-called model organisms in it, with the help of which it is possible to study the nature of various diseases, and the studies were conducted not on the already familiar transgenic mice, but on plants and yeast.

Malformations and plants

It would seem that in order to investigate the causes of human diseases, it is necessary to work directly with patients. However, if you type the phrase Alzheimer's disease ("Alzheimer's disease") in the PubMed search engine, we will see that in a considerable part of the work, mice, not people, were the object of research. Many other diseases will give similar results.

The fact is that many diseases and congenital disorders are associated with the malfunction of genes, which leads to a deficiency or excess of certain proteins, disruption of their normal functioning and, as a result, to failures at the level of the whole organism. And if you take a mouse, deprive it of certain genes or embed new genes in its body, presumably associated with the development of the disease, then the genetic basis of the disease can be determined by the state of the rodent.

Such experiments are naturally impossible on humans, both from an ethical and technical point of view. And mice reproduce quickly, are relatively easy to maintain, and their genome has long been learned to change in one direction or another. From an ethical point of view, there are far fewer questions about experiments on mice than in the case of experiments on monkeys, especially since one mouse slaughtered in the laboratory will benefit humanity more than hundreds of hunted urban rodents in basements.

But if it is known that certain genes can be the cause of certain disorders, then what prevents them from being studied in other organisms? Doctors and biologists have been asking themselves this question almost since the advent of genetic engineering, and not in vain – today there are even plants designed to help in understanding birth defects of development.

For example, Waardenburg syndrome is a rare disease characterized by congenital deafness and deformity of the skull bones. Such a violation occurs due to a malfunction in the genes that control cell migration during embryonic development, and since cell migration is a fairly universal process, it can be studied on almost any complex multicellular organism. Including on arabidopsis, known as the Tal's rhesus (Arabidópsis thaliána).

In this plant, prized by botanists for the comparative simplicity of the genome and rapid growth, a human gene suspected of developing Waardenburg syndrome also caused a developmental disorder. The plant could not orient itself correctly in the gravity field.

Having a fast-growing multicellular organism that reproduces the disease of interest to scientists, you can try to fight it by affecting other genes.


Embryos of the spur frog:
on the left – normal, on the right – mutant, which studies heart defects in humans.

Against the background of Tal's rhesus, which helps biologists understand congenital deafness, experiments with Xenopus frogs designed to find out the cause of heart defects are no longer particularly impressive. Another thing is to use yeast to study Zelwiger syndrome, a rare hereditary disease in which there is a whole bunch of disorders, from enlarged liver to visual impairment.

One cell is enough
 
The most diverse syndromes manifested in Zelwiger syndrome and some other diseases have been reduced by scientists to a malfunction at the intracellular level. Studies have shown that in patients, the work of peroxisomes (microscopic bubbles with enzymes) is disrupted, with the help of which the cell conducts a number of oxidative reactions.

Since the root of the problems lies inside individual cells and has nothing to do with their interaction, then maybe the problem can be reproduced at all on single-celled organisms? Why make mutant mice when you can do, for example, yeast? Biologists reasoned something like this, after which even yeast joined the number of model organisms. For example, they are now investigating amyotrophic lateral sclerosis, a disease that caused paralysis in the famous astrophysicist Stephen Hawking.

However, it is still necessary to make an explanation: hypotheses of the occurrence of the disease are most often tested on model organisms. The final selection of drugs, the development of new methods of operations – all this requires either larger animals or direct clinical trials. But primary medical research can now be carried out in laboratories where there are not only patients, but also animals familiar to us like mice, rats or rabbits.

Portal "Eternal youth" http://vechnayamolodost.ru08.04.2010

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