This web page was produced as an assignment for Genetics 564, an undergraduate capstone course at UW-Madison.
What is Chemical Genomics? [1]
Figure 1: Chemical Genomics Outcomes
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Chemical genomics is the type of study that utilizes target-specific chemical ligands known in chemical libraries to study gene and protein functions. Chemical genomics can provide high throughput screens in various model organisms. In these screens, scientists apply various chemical ligands and screen for a phenotype of interest, biological function, or new drug discovery. These screens can look for chemicals that can restore the wild type phenotype and suggest a potential drug to be used in disease treatment.
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What is the general overview of a chemical genomic screen? [1]
Reverse chemical genetics begin with establishing a role for a protein in a pathway or disease, identifying candidate small molecules, and then validate cellular activities of candidates. Forward chemical genetics begin with a phenotype in a model organism and an assay for small molecules that can restore a wild type phenotype. After this identification, candidate small molecules must then undergo target-identification and mechanism-of-action studies. Small molecules are usually selected from a chemical library, like Pubchem or Chemspider. An example of a chemical screen can be shown in Figure 3. In this forward chemical screen, scientists used two different phenotypes associated with wild type structure in zebrafish to identify restoration of a wild type phenotype. These screens can utilize known drugs or small molecules that can help identify potential therapeutic targets.
Drug Databases:
Conclusion
Zebrafish can provide a great tool for understanding if known chemical compounds can restore wild type function and structure. To my knowledge, there has not been any published articles on chemical compounds targeting DNA repair in FUS-ALS. Researcher working on understanding DNA repair in ALS have stated that chemical genomics could be the next step for understanding the role of FUS in DNA repair [2]. The current direction is to use various chemical compounds known to upregulate DNA repair proteins and downregulate pathway inhibitors. From this regulation, one could potentially restore DNA repair to prevent upstream aggregation and motor neuron defects. By using this technique in my Aims 2, I would be able to find evidence of additional interactions of FUS in DNA repair and provide a way of preventing these downstream effects like neurodegeneration from occurring.
References
1. Zheng, X.S. & Chang, T.F. (2002, April). Chemical Genomics: A Systematic Approach in Biological Research and Drug. Current Issues Molecular Biology 4:33-43.
2. Dance, A. (2018, March). Targeting FUS: DNA Damage Control in ALS. Retrieved on 4/12/2019 from
http://www.alsresearchforum.org/targeting-fus-dna-damage-control-in-als/
Header Image: https://68.media.tumblr.com/50cebea2908567552e9033514506c458/tumblr_oi56ylQmGf1uc25l0o1_1280.jpg
Figure 1: http://web.yonsei.ac.kr/cglab/images/genomics.gif
Figure 2: https://www.nature.com/articles/nchembio.1199
Figure 3: https://encrypted-tbn0.gstatic.com/images?q=tbn:ANd9GcS8vECOHxKovfcAULmGlJgNikYEiCMSBjjnuhsqXOB7J17TOyS_8A
2. Dance, A. (2018, March). Targeting FUS: DNA Damage Control in ALS. Retrieved on 4/12/2019 from
http://www.alsresearchforum.org/targeting-fus-dna-damage-control-in-als/
Header Image: https://68.media.tumblr.com/50cebea2908567552e9033514506c458/tumblr_oi56ylQmGf1uc25l0o1_1280.jpg
Figure 1: http://web.yonsei.ac.kr/cglab/images/genomics.gif
Figure 2: https://www.nature.com/articles/nchembio.1199
Figure 3: https://encrypted-tbn0.gstatic.com/images?q=tbn:ANd9GcS8vECOHxKovfcAULmGlJgNikYEiCMSBjjnuhsqXOB7J17TOyS_8A