This project was built upon a previous study (Johansson et al.2020) that tested multiple drugs on glioblastoma cell lines and found a big division between the drug response for proteasome inhibitors. The aim of this project was to try to obtain a better insight into the differences between the two drug response subgroups’ processes by creating and comparing two genome scale metabolic models (GEMs) of the two subgroups. To do this, genomescale metabolic models were made for each cell line and later merged after its proteasome inhibitor response to obtain two general models. After having multiple models for each cell line and two general drug response models, comparisons could be made. Overall, the differences between cell lines were larger than the differences between drug responses, but some differences could still be seen. Some differences in the number of reactions in subsystems were found between the two general GEMs, where the Ureacycle subsystem showed the largest difference between the two models. Another difference was in the metabolic activity of the models, where the sensitive model passed ten tasks which the resistant model could not. The last and the most important comparison was essentiality analysis which gave a multitude of essential genes but only twelve genes that were unique to the twogeneral GEMs. Nine genes for the resistant model and three for the sensitive. Out of these genes CYP51A1 and FDFT1, for the resistant model, and genes RBP1 and CYP27A1, for the sensitive model, had already been in at least one study regarding Glioblastoma or Proteasome Inhibitors. Since some of the found genes already seem to have been found interesting for PIs or glioblastoma treatment the unique genes from the essentiality analysis could be interesting to look more into in the future.
| Identifer | oai:union.ndltd.org:UPSALLA1/oai:DiVA.org:uu-450089 |
| Date | January 2021 |
| Creators | Bernedal Nordström, Clara |
| Publisher | Uppsala universitet, Institutionen för farmaceutisk biovetenskap |
| Source Sets | DiVA Archive at Upsalla University |
| Language | English |
| Detected Language | English |
| Type | Student thesis, info:eu-repo/semantics/bachelorThesis, text |
| Format | application/pdf |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | UPTEC X ; 21016 |
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