Re-awakening enemy sleepers…

The idea of an enemy sleeper agent is a central plot device in many a spy novel or movie, and certainly the idea of going to ground behind enemy lines is not unheard of in many theatres of conflict. The idea in all cases is to remain undetected until re-activated to cause harm behind enemy defences.

The trick to identifying if there are latent sleepers operating is to try and re-activate them and get them to reveal themselves. Cue any number of spy stories about false radio signals or targets to lure sleepers into the open.

Curiously, it is a similar strategy that is being used in novel treatments for infections from two disparate areas of chemotherapy, one in the treatment of HIV and the other the treatment of persistent bacterial infections.

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Re-awakening ancestral genes…

Research bloggingHUMANS, as we know, are the product of tens of thousands of genes, but hidden elsewhere in your DNA are genes that are no longer functional; these vestigial genes are known as pseudogenes, and they are ancestral remnants from an earlier point in our evolution. In many cases they are simply inactivated duplicates of a current functional gene. In other cases they are genes that have been cut out, reversed and stitched back in; in this position, some believe they may act to regulate the correctly oriented ‘functional’ version of the gene. Alternatively, they may be ancestral genes encoding functions that have become inactive beacuse they are ultimately not necessary for survival. Now, what if we could turn on one of these ancestral genes? One that could actually help protect us from a modern day infection?

In the recent edition of PLoS Biology is an interesting study that describes the re-activation of just such a dormant human pseudogene, retrocyclin, and its potential use as a defensive barrier against infection with HIV-1 (a strain of the Human Immunodeficiency Virus that causes AIDS). Retrocyclin is theta-defensin, which are naturally produced, circular chains of 18 amino acids (a peptide). I have previously research blogged about the application of other such antimicrobial peptides.

Active, functional theta-defensins have only so far been identified in the old world monkeys: the Rhesus Macaque and Olive Baboon; in Humans and other primates, they exist as pseudogenes. At some point in evolutionary history, our ancestors started inheriting a genetic mutation, all be it one that exists at 100%. The Human version of the gene, retrocyclin, is inactive in Humans because of a premature ‘stop’ signal, which makes the cell abandon the production of the peptide too early.

Retrocyclin can be synthesised chemically in a lab, and in this manner that the authors of this paper (from laboratories at the University of Central Florida and UCLA) have previously shown that it is capable of inactivating HIV-1, thereby preventing its entry into cells; in fact, they have also shown that it can similarly prevent entry of Herpes Simplex Virus type I (responsible for coldsores) and type II (responsible for genital warts).

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