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'''Project Idea: Use of a Virus-injected Vector to Create Serotonin-Creating Biodevices'''
'''Project Idea: Use of a Virus-injected Vector to Create Serotonin-Creating Biodevices'''
We will use a virus to inject into mice brains to induce the creation of serotonin-creating biodevices.  The biodevices will consist of a genetic circuit which is sensitive to the serotonin levels present in the brain.  If a sufficiently low level of serotonin is being made, expression of a part of the genetic circuit will allow for the production of serotonin.


The vector will consist of a serotonin-sensing receptor coding region (specified by Dr. Hellinga in the article available at http://www.dukemednews.org/news/article.php?id=6549), which will be able to sense the levels of serotonin in the environmentThis would be connected to a constitutive promoter in order for the protein to be synthesized continuously.  The receptor coding region will then be connected to an inverter which will create a high PoPs signal when serotonin levels are low.  This inverter will lead to the coding regions of two enzymes, both responsible for the conversion of tryptophan to serotonin.  Since excess tryptophan is available in the brain, such a system should be feasible.
We will use a virus to inject into mice brains a vector containing serotonin-creating biodevices.  The biodevices will consist of a genetic circuit which is sensitive to the serotonin levels present in the brainIf a sufficiently low level of serotonin is being made, expression of a part of the genetic circuit will allow for the production of serotonin.


The reason why such a system would be useful is that many mental disorders, including depression and obsessive-compulsive disorder, result from abnormal serotonin production in the brain.  This system would allow for  increased production of serotonin when serotonin levels are low in the mouse brain, which would certainly be a substantial step in the development of theorapies for these mental disorders in humans.
The vector will consist of a serotonin-sensing receptor coding region (specified by Dr. Hellinga in the article available at http://www.dukemednews.org/news/article.php?id=6549), which will be able to sense the levels of serotonin in the environment.  This would be connected to a constitutive promoter in order for the protein to be synthesized continuously. The receptor coding region will then be connected to an inverter which will create a high PoPs signal when serotonin levels are low.  This inverter will lead to the coding regions of two enzymes, both responsible for the conversion of tryptophan to serotonin (see the biochemistry section of http://en.wikipedia.org/wiki/Serotonin).  Since excess tryptophan is available in the brain, such a system should be feasible.


If everything goes according to plan, such a goal would be accomplished, and we could then try to move to working with the human brain.  Challenges in accomplishing this goal is the following.  Although viruses have been used to carry vectors to neurons in the brain before (most notably, Larry Young used viruses to transfect prairie voles' brain cells with a gene that made the animals monogamous, see http://www.nature.com/news/2001/010927/full/010927-4.html;jsessionid=D8FFD24796C542BBDC34656E498280DD), the feasibility of such a feat in mouse brains is uncertain.  The making of the genetic circuit will probably be the easiest step as genetic circuits have become increasingly easy to manufacture with the advent of DNA synthesis technology.  The worst case scenario would be that the viruses are unable to transfect the cells with the vector.  Thus, the worst possible outcome will probably be that we will need to find another model organism, such as the prairie vole, or to find another way of transfecting mouse brain cells.  
The reason why such a system would be useful is that many mental disorders, including depression and obsessive-compulsive disorder, result from abnormal serotonin production in the brain.  This system would allow for increased production of serotonin when serotonin levels are low in the mouse brain, which would certainly be a substantial step in the development of therapies for these mental disorders in humans. 
 
If everything goes according to plan, such a goal would be accomplished, and we could then try to move to working with the human brain.  The challenge in accomplishing this goal is the following.  Although viruses have been used to carry vectors to neurons in the brain before (most notably, Larry Young used viruses to transfect prairie voles' brain cells with a gene that made the animals monogamous, see http://www.nature.com/news/2001/010927/full/010927-4.html;jsessionid=D8FFD24796C542BBDC34656E498280DD), the feasibility of such a feat in mouse brains is uncertain.  The making of the genetic circuit will probably be the easiest step as genetic circuits have become increasingly easy to manufacture with the advent of DNA synthesis technology.  The worst case scenario would be that the viruses are unable to transfect the cells with the vector.  Thus, the worst possible outcome will probably be entail an additional search for another model organism, such as the prairie vole, or to find another way of transfecting mouse brain cells.  


The above resources will be integral to the accomplishment of a research goals.
The above resources will be integral to the accomplishment of a research goals.

Revision as of 09:35, 5 May 2006

Project Idea: Use of a Virus-injected Vector to Create Serotonin-Creating Biodevices

We will use a virus to inject into mice brains a vector containing serotonin-creating biodevices. The biodevices will consist of a genetic circuit which is sensitive to the serotonin levels present in the brain. If a sufficiently low level of serotonin is being made, expression of a part of the genetic circuit will allow for the production of serotonin.

The vector will consist of a serotonin-sensing receptor coding region (specified by Dr. Hellinga in the article available at http://www.dukemednews.org/news/article.php?id=6549), which will be able to sense the levels of serotonin in the environment. This would be connected to a constitutive promoter in order for the protein to be synthesized continuously. The receptor coding region will then be connected to an inverter which will create a high PoPs signal when serotonin levels are low. This inverter will lead to the coding regions of two enzymes, both responsible for the conversion of tryptophan to serotonin (see the biochemistry section of http://en.wikipedia.org/wiki/Serotonin). Since excess tryptophan is available in the brain, such a system should be feasible.

The reason why such a system would be useful is that many mental disorders, including depression and obsessive-compulsive disorder, result from abnormal serotonin production in the brain. This system would allow for increased production of serotonin when serotonin levels are low in the mouse brain, which would certainly be a substantial step in the development of therapies for these mental disorders in humans.

If everything goes according to plan, such a goal would be accomplished, and we could then try to move to working with the human brain. The challenge in accomplishing this goal is the following. Although viruses have been used to carry vectors to neurons in the brain before (most notably, Larry Young used viruses to transfect prairie voles' brain cells with a gene that made the animals monogamous, see http://www.nature.com/news/2001/010927/full/010927-4.html;jsessionid=D8FFD24796C542BBDC34656E498280DD), the feasibility of such a feat in mouse brains is uncertain. The making of the genetic circuit will probably be the easiest step as genetic circuits have become increasingly easy to manufacture with the advent of DNA synthesis technology. The worst case scenario would be that the viruses are unable to transfect the cells with the vector. Thus, the worst possible outcome will probably be entail an additional search for another model organism, such as the prairie vole, or to find another way of transfecting mouse brain cells.

The above resources will be integral to the accomplishment of a research goals.