Xinyi and Dianna will be presenting the following papers:
Asad Z, Sachidanandan C. Chemical screens in a zebrafish model of CHARGE syndrome identifies small molecules that ameliorate disease-like phenotypes in embryo.Eur J Med Genet. 2020 Feb;63(2):103661. doi: 10.1016/j.ejmg.2019.04.018. Epub 2019 May 1. PMID: 31051269 Review: •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. Epub 2018 May 23. *Identifying Novel Cancer Therapies Using Chemical Genetics and Zebrafish. https://www.ncbi.nlm.nih.gov/pubmed/27165351 *Chemical genetic screening in the zebrafish embryo. https://link.springer.com/chapter/10.1007%2F978-3-319-30654-4_5 *Animal models of human disease: zebrafish swim into view. https://www.nature.com/articles/nrg2091 Using zebrafish to model autism: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7686559/
17 Comments
HUIXIAN QIU
3/3/2024 09:44:58 pm
How do you compare small molecule screening with western blot, which is also used to examine the roles of molecules in certein physiological process?
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Rebecca Wright
3/4/2024 10:49:49 am
The Asad et al. paper discusses various small molecule drugs that can partially rescue symptoms of CHARGE syndrome, particularly in craniofacial tissues such as cartilage. Has any further work been done on how these small molecule drugs impact other symptoms of CHARGE syndrome, such as heart defects?
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Perla Larios
3/5/2024 12:02:30 pm
As I was reading this I was wondering if they were able to just shutdown CHD7 go in with CRIPRa and up regulate the promoter on the gene closes it that is in the same pathway.
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perla larios
3/5/2024 12:09:37 pm
Sorry, the question is why was this choosen as the best? what other methods where considered?
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Brooke Fuerstenau
3/6/2024 05:34:52 pm
So if these studies were to be used to help treat/manage symptoms of CHARGE, would they be able to implement all of these small molecules that they found to help in one treatment/procedure and fix most of if not all of the issues that come with this disorder?
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Sara Fritz
3/6/2024 06:02:38 pm
Did the researchers confirm or is it already proven that CHD7 mutants are haploinsufficent? Additionally, for the small molecules they identified that helped to rescue some phenotypes, are these molecules in some way modifying chromatin structure the way the CHD7 protein would? Do we know by what mechanisms these molecules could be acting?
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Joely
3/6/2024 08:18:44 pm
In the article about small-molecule screening, it goes over the difference between target-based biochemical assays and cell-based phenotypic assays. Both can be used to determine protein interactions, is there a reason you would want to use one or the other?
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Rohan Babaria
3/6/2024 11:02:10 pm
In the study they mention using 5uM of chemicals- I was wondering if this would overlook dosage dependent effects that could change the interactions (such as threshold values).
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Michelle Conte
3/6/2024 11:57:30 pm
Is there such thing as excess-myelination of the neuron and can that have negative consequences?
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Zoe Zwick
3/7/2024 12:24:47 am
One thing that the review mentioned was that many therapeutics derived from chemical screens fail at later stages of clinical development. Do you know if any further testing has been done with these chemicals to see if there are any clinical uses for them in CHARGE patients?
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Samuel Kivi
3/7/2024 12:56:46 am
What other model organisms would be better for different types of human genetic disease homologs? Are there any particular organs/organ systems that aren't homologous in model organisms compared to humans?
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3/7/2024 09:53:27 am
In the main reading for today, why did they use different amounts of hpf for cartilage than neuron and myelination well plates?
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Julia Carey
3/7/2024 11:17:11 am
Can you only use small-molecule screening for diseases/traits that are monogenic? Why or why not?
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Praneeth Venigalla
3/7/2024 11:21:21 am
What are the specific advantages and limitations of using zebrafish for modeling human diseases, particularly in terms of translational research? How do these factors impact the potential for discovering and validating new treatments for conditions such as CHARGE syndrome, cancer, and autism?
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Miles Giehtbrock
3/7/2024 11:29:38 am
In the "Using Zebrafish to Model Autism Spectrum Disorder: A Comparison of ASD Risk Genes Between Zebrafish and Their Mammalian Counterparts" They mention "genetic compensation" when talking about the disadvantages of morpholino oligomer injections to induce RNAi.This is the first that I have heard of this. Do you know what mechanisms cause this?
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Kate Stack
3/7/2024 11:45:07 am
I found using zebrafish as a model organism to study autism to be really interesting! What is the incidence of the behavioral traits such as shoaling behavior or wall hugging in non-genetically modified zebrafish? Are any of the genes mentioned found to be commonly mutated in zebrafish?
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Madeline Blum
3/7/2024 11:47:44 am
In Markossian et al., there seems to be a hopeful outlook on a switch from using model organisms in small- molecule screening to engineered patient- derived cells. In what situations would animal derived cells be a better option, considering animal models are still used?
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