This web page was produced as an assignment for Genetics 564, an undergraduate course at UW-Madison.
Chemical Genetics
Creating mutations to alter gene expression has been a very powerful tool for studying genes and systems. However, this method is more difficult to use in mammals due to their slower reproductive rates and large genomes [1]. Chemical genetics provides an alternative method to directly altering the genetic sequence. Instead of mutations, chemical genetics uses small organic molecules to obtain information about the molecular mechanisms behind biological processes [1]. These small molecules can take the place of mutations because they can bind to proteins and change their activity levels, such as inhibiting or activating them. Chemical genetics can also provide more specific results because it is possible to find a small molecule that alters only one or specific functions of a protein with many functions [1]. This would produce a phenotype that is only due to the altering of specific paths and could provide great insight, as opposed to simply eliminating any protein function of that gene and not knowing which activities to attribute the resultant phenotypes to. Chemical genetics can also be used to discovery new drugs or drugs that are more effective at binding the desired protein. In fact, there are now virtual libraries of small molecules that store the shapes of these molecules and thus can be used to determine which shape will produce the desired interaction with the target protein [2].
Small Molecules and TOP3β
I searched for small molecule interactions with TOP3β on both PubMed and ChemBank, two online databases for chemical genetics. However, I did not obtain any small molecule results. My guess is that this area has not been greatly studied yet since the connection between TOP3B and schizophrenia is very recent.
Analyzing my Lack of Findings
The antipsychotic drugs currently used to treat schizophrenia do not directly affect genes. Instead they alter levels of neurotransmitters in the brain, such as dopamine and serotonin, which then regulates behavior, mood, and emotions [3]. These drugs have numerous and varying side effects and do not work well for everyone. The fact that there are many different genetic and environmental factors that influence schizophrenia could explain why these drugs, which only work in a singular, indirect manner, produce different results for everyone. Certainly the causes of schizophrenia, such as a TOP3B deletion, could affect more things in the body than just neurotransmitter levels. Perhaps by better understanding how TOP3B influences schizophrenia, we could develop a new treatment method that would more effectively help those with schizophrenia. This could involve expanding the the study of chemical genetics on TOP3β, which is currently lacking, and find drugs or small molecules that do directly interact with TOP3β.
References
[1]. Stockwell BR. Exploring biology with small organic molecules. Nature. 2004 Dec 16;432(7019):846-54. Review.
[2]. Your World: Biotechnology and You. Searching for Drugs. 1999. vol. 9, issue 1. pp 12-13. retrieved Apr 18, 2014. http://www.biotechinstitute.org/download/files/YourWorld/yw-91-computer.pdf
[3]. Patient.co.uk. Antipsychotic Medicines. retrieved Apr 18, 2014. http://www.patient.co.uk/health/antipsychotic-medicines
[image] http://www.utoronto.ca/boonelab/research_projects/chemical_genetics/interaction_networks/
[2]. Your World: Biotechnology and You. Searching for Drugs. 1999. vol. 9, issue 1. pp 12-13. retrieved Apr 18, 2014. http://www.biotechinstitute.org/download/files/YourWorld/yw-91-computer.pdf
[3]. Patient.co.uk. Antipsychotic Medicines. retrieved Apr 18, 2014. http://www.patient.co.uk/health/antipsychotic-medicines
[image] http://www.utoronto.ca/boonelab/research_projects/chemical_genetics/interaction_networks/