What is Chemical Genomics?
Chemical genomics is the study of how small compounds (molecules) interact with a biological system as chemical modifications. This type of study uses large-scale protein analysis and can be done in reverse and forward genetic approaches [1]. In a reverse chemical genetic screen, the protein of interest is used to find the compound of interest. The compounds of interest bind to the protein of interest and are then used in living systems to observe the biological response. Chemical libraries in living systems are used to find compounds of interest in a forward chemical genetic screen. These compounds of interest will allow you to find your protein of interest. The compound found can either inhibit or stimulate the function of your protein of interest [2]. The compounds of your protein of interest can be searched through the PubChem website.
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Discussion
There are two inhibitory compounds that were identified in PubChem, which are Fumarate hydratase-IN-1 and Fumarate hydratase-IN-2 [3]. This means that there are two possible enzymes that are involved with the conversion of Fumarate to Malate. If there is a knockout of the FH gene, one or both of these compounds could be modified to rescue the mutant phenotype. Knowing which compound that is responsible for this rescue, will give us insight on how mitochondrial homeostasis effects kidney cells.
Resources:
[1] Sasson, I. E., & Taylor, H. S. (2008). Stem cells and the pathogenesis of endometriosis. Annals of the New York Academy of Sciences, 1127, 106–115. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3107843/#:~:text=The%20endometrium%20is%20broadly%20composed,and%20the%20supporting%20mesenchymal%20cells.
[2] Thorpe DS. Forward & reverse chemical genetics using SPOS-based combinatorial chemistry. Comb Chem High Throughput Screen. 2003;6(7):623-647. doi:10.2174/138620703771981205
[3] PubChem. (n.d.). PubChem- Fumarate Hydratase. National Center for Biotechnology Information. PubChem Compound Database. https://pubchem.ncbi.nlm.nih.gov/#query=Fumarate%20hydratase
[2] Thorpe DS. Forward & reverse chemical genetics using SPOS-based combinatorial chemistry. Comb Chem High Throughput Screen. 2003;6(7):623-647. doi:10.2174/138620703771981205
[3] PubChem. (n.d.). PubChem- Fumarate Hydratase. National Center for Biotechnology Information. PubChem Compound Database. https://pubchem.ncbi.nlm.nih.gov/#query=Fumarate%20hydratase
This web page was produced as an assignment for Genetics 564, a capstone course at UW-Madison.