Chemical Genomics
Introduction
Chemical genomics is the study of how small molecules impact biological processes to better understand biomolecular relationships. [1] Chemical genetic screens can test hundreds of different molecules to study the molecules' effect on different stages of development, ability to rescue wildtype phenotypes when applied to mutants, or ability to generate novel phenotypes. [2] These screens can sometimes identify new medications or chemical therapeutics that can be used to address genetic diseases and disorders or to identify relationships between pathways.
Results
Using my model organism, the zebrafish, a chemical genetic screen could be used with embryos that have had their ROBO3 genes edited using CRISPR/Cas9. These embryos could then be exposed to a broad spectrum, diversity-based chemical library - as there is no established target molecule as of yet to start testing with. After exposure, the surviving embryos could be analyzed during early nervous development to see if any of the mutants rescued the wildtype arrangement of commissural axons. This would result in a "chemical hit". These chemicals/small molecules could then be followed up with more specific assays could be done to better understand the molecule's relationship with ROBO3 and its mutated phenotypes.
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Discussion
There is currently no known association between ROBO3 or synesthesia and a chemical agent or small molecule. However, a carefully-designed chemical genetic screen could elucidate a relationship.
References
- Markossian, S, et al. Small-Molecule Screening for Genetic Diseases. Annu Rev Genomics Hum Genet. 2018 Aug 31;19:263-288. doi: 10.1146/annurev-genom-083117-021452.
- Kaufman, C K, et al. Chemical genetic screening in the zebrafish embryo. Nature Protocols. 2009 Sept 10;4:1422–1432. https://doi-org.ezproxy.library.wisc.edu/10.1038/nprot.2009.144
- Kithcart, A, et al. Using Zebrafish for High-Throughput Screening of Novel Cardiovascular Drugs. JACC: Basic to Translational Science. 2017;2:1-12. doi.org/10.1016/j.jacbts.2017.01.004.