Browsing by Author "Marcette, Jana"

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Investigating the Potential Anticonvulsant Effects of Taxol Through Microtubule Stabilization in C. elegans Model of Epilepsy
(Montana State Univeristy Billings, 2024) Elbert, Madelyne; Marcette, Jana
Recent discoveries have unveiled a mutation in the CAMSAP gene as a causative factor in a distinct form of epilepsy. CAMSAP's pivotal role in microtubule stabilization and cellular signaling underscores its significance in neuronal function. This experiment poses to answer the question: Does the stabilization of microtubules stop the progression of convulsions for a specific type of epilepsy? Microtubules orchestrate the spatial organization within cells, essential for cellular integrity and function. Perturbations in microtubule dynamics, marked by instability and subsequent shrinkage due to GTP hydrolysis, can precipitate cellular dysfunction. To address this, we propose the application of Taxol, a renowned microtubule-stabilizing agent, in a C. elegans model. Leveraging the simplicity of C. elegans' nervous system, we aim to elucidate Taxol's potential in mitigating seizures induced by a specified solution. Through systematic observation at five and ten-minute intervals, we anticipate Taxol's intervention to stabilize microtubules and ameliorate convulsions. This research offers a promising avenue for understanding the molecular underpinnings of epilepsy and exploring therapeutic interventions targeting microtubule dynamics.
The effects of Quercetin on seizure like activity in Caenorhabditis elegan mutants
(2024) Worden, Braiden; Marcette, Jana
Our experiment on Caenorhabditis elegans was the first step in providing relief for patients with a clinically recognizable neuronal migration disorder caused by CAMSAP1 mutations. CAMSAP1 is thought to stabilize microtubule minus ends and to be involved in cell signaling. There are currently no treatments for this disorder. Thus, we partnered with the undiagnosed disease network at Washington University School of Medicine for this project. Our goal was to find a drug that will help patients with this disorder. We picked C. elegans because they have a homolog for the CAMSAP1 gene called PTRN-1. The worms were grown on NGM (Nematode Growth Medium) plates without calcium. This was how we got them to have convulsion, which presented themselves when we put them in a buffer (100 mM NaCl, 50 mM MgCl2.) We delivered the drugs into the worms by using a "spot dead" method, where we put a drop of the tested drug onto the plate and covered it in dead E. coli. The worm then eats the dead E. coli, ingesting the drug with it. This method directly bypasses the cuticle of the worm, meaning less of each drug had to be used. The experiment overall was a resounding success, as a handful of the drugs we tested rescued the mutants. This includes Quercetin, which was the drug I chose. It was picked due to its ability to downregulate cell signaling pathways impacted by CAMSAP, specifically DAPK and MAP3K12. The drugs that rescued will be tested on a vertebrate model organism next, and if all goes well, it can be given to the children to help them. This experiment was the first step in the journey of helping these kids with an incredibly debilitating disorder.