Genetic Lego

My mother, like I imagine most mothers do, has pictures of me and my brother on her desk at work. When interested parties (inevitably other mothers) ask what we do for our livings, she tells them she has one son that’s a “computer geek,” and another that’s “Dr. Frankenstein.” Clearly I’m the one who has the dubious honour of being referred to as “doctor” by my mother even before I have finished my degree. She’s obviously very proud.

While I don’t cackle madly over experiments performed in thunderstorms on the roof of Lehmann Pavilion – and I sure don’t get an Igor to help me with my lab work – I do get to do some fairly wild and freakish stuff sometimes. The most wild and freakish of those things would be the experiments I perform using lentivirus.

The main reason people find these experiments so freaky is because the primary tool, the lentivirus itself, is derived from the HIV virus that causes AIDS. We use a strain that has been heavily engineered into a sort of genetic Lego set that can perform some pretty amazing tricks for us, while eliminating many of the health risks you would expect to be a problem when working with something like the HIV virus.

HIV is an amazing organism, which is probably part of why it causes such a devastating disease. I have mentioned before that, in the dogma of biology, we have genes in our DNA that go on to make mRNA “middlemen,” which then go on to make the proteins that perform the actual work inside a cell. HIV caused gigantic waves through the biology community because it works in reverse: the virus contains the genetic material to make more of itself stored in an RNA form. Once inside a host cell, special enzymes take that RNA and turn it into DNA that gets inserted into the DNA of the host cells. The host cells then make more copies of the virus, which go out into the organism and infect more cells.

The most important thing about this from my perspective is that the virus is capable of inserting genes into a host cell’s normal DNA. Recognizing that this could be a powerful tool for biology, people have been working for the last 15 years or so on how to harness the properties of this virus. What we work with now are 3 or 4 engineered “chunks” of that viral genetic code that we can put into cells. These cells are then forced to produce a virus that can introduce itself into a host cell and place genes into their DNA, but can’t make more of itself. This precaution helps keep the experimenters safe in case there is accidental exposure.

Two or three of those chunks are the same no matter what you want your virus to do. They have what the virus needs to assemble itself into a functioning unit that can insert DNA into a host cell. The last chunk is the important one. It contains the gene you want to insert into the infected cells. This is why it’s a little like a Lego set – you can switch your components to change what gene you want to deliver.

The best thing about this brand of Lego from the viewpoint of mental health research is that we can test hypotheses about the contribution of genes to different aspects of various disorders. For example, we can test if a gene is involved in anxiety by putting that gene in a lentivirus and infecting an animal with it. Then we confirm that the gene and its products are present in higher amounts and test an animal for fearful behaviour. Similarly, there are other tools we can put into that last chunk of lentivirus Lego that prevent a gene from expressing its products. This is a very powerful approach to discovering how a specific gene might contribute to a given mental disorder.

Using approaches like this, researchers hope to develop methods to help patients at the genetic level. For example, altering the expression of genes involved in the stress response might be able to help patients with anxiety disorder, or manipulating genes important for memory may one day help those with learning disabilities. Similarly, these techniques could be used to help patients with purely genetic diseases like Huntington’s.

One caveat, however, is that mental disorders are almost never so simple that changing the expression of a single gene will solve any of the problems a patient might have. There is no gene for happiness, or schizophrenia, or even calmness for that matter. If it were that easy, there would be no more problems in mental health, and a lot of people like me would be out of a job. Sadly, we are all aware that this is not the case.

Still, understanding the contributions of different gene products to various behaviours is vital for improving strategies for the treatment of psychiatric disorders. The genetic Lego set provided by the lentivirus allows us to do just that – manipulate some of the base building blocks of life to open avenues for better understanding of the brain, and suggest new treatments in the field of mental health. I realize this is nowhere near so exciting as lightning storms and maniacal laughter, but please believe me when I say that the research community is more than willing to sacrifice a little excitement in the name of science. In fact, it’s a job requirement.

I do wish I had an Igor, though.

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Posted in General science, Molecular biology.

Posted on 10 Jun 2009

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